Cardiovascular Physiology

Answer Card

Cardiovascular physiology encompasses the study of cardiac function, coronary circulation, and systemic haemodynamics. Key concepts include the cardiac cycle, pressure-volume loops, Frank-Starling mechanism, coronary perfusion dynamics, myocardial oxygen balance, autonomic regulation, and determinants of blood pressure.

Core Principles:

Cardiac cycle: Systole (isovolumic contraction, ejection) and diastole (isovolumic relaxation, filling) with precise valve timing
Pressure-volume loops: Graphical representation of ventricular pressure-volume relationships; areas represent stroke work and stroke volume
Frank-Starling law: Ventricular stroke volume increases in response to increased preload (end-diastolic volume) within physiological limits
Coronary perfusion: Predominantly occurs during diastole; perfusion pressure = aortic diastolic pressure - LVEDP; affected by intramural pressure and autoregulation
Myocardial oxygen consumption: Determined by heart rate, contractility, and wall tension; MVO₂ increases linearly with pressure-volume area
Autonomic nervous system: Sympathetic increases heart rate, contractility, and conduction velocity; parasympathetic decreases heart rate and AV nodal conduction
Baroreceptor reflexes: Carotid sinus and aortic arch receptors respond to pressure changes; mediate short-term blood pressure regulation
Determinants of MAP: Mean arterial pressure = Cardiac output × Systemic vascular resistance

Clinical Overview

Cardiovascular physiology forms the foundation of critical care practice, informing haemodynamic monitoring, vasoactive drug therapy, and cardiopulmonary resuscitation. Understanding normal cardiac function is essential for interpreting abnormal physiology in shock states, cardiac failure, and post-cardiac arrest care.

The heart functions as a sophisticated pump, converting metabolic energy to mechanical work through cyclic contraction and relaxation. The cardiac cycle coordinates electrical depolarisation, valve function, and pressure changes to maintain continuous forward blood flow. Pressure-volume analysis provides a comprehensive framework for understanding ventricular performance, encompassing preload, afterload, contractility, and the relationships between pressure, volume, and work.

Coronary circulation presents unique physiological challenges because the heart must pump blood to itself against high intramural pressures. Unlike other organs, coronary perfusion occurs predominantly during diastole when myocardial resistance decreases. The oxygen extraction ratio of the myocardium is exceptionally high at 70-80%, meaning that increased oxygen demand must be met by increased coronary blood flow rather than increased extraction. This explains why myocardial ischaemia can develop rapidly in states of high demand or impaired supply.

The autonomic nervous system provides beat-to-beat regulation of cardiovascular function. Sympathetic activation via norepinephrine and epinephrine increases cardiac output and redirects blood flow to vital organs during stress states. Parasympathetic tone via the vagus nerve dominates at rest, maintaining low heart rates and high vagal tone which is protective against arrhythmias. The balance between these systems determines baseline cardiovascular status and response to physiological stressors.

Baroreceptor reflexes provide rapid blood pressure regulation, operating on timescales of seconds to minutes. Carotid sinus and aortic arch receptors sense stretch and signal via the nucleus tractus solitarius to adjust sympathetic and parasympathetic output. In intensive care patients, this reflex can be impaired by sedation, neurological injury, or chronic hypertension with baroreceptor resetting.

Cardiac Cycle

The cardiac cycle consists of systole and diastole, each divided into distinct phases characterised by pressure changes, valve movements, and volume shifts. Understanding the timing and pressure relationships within the cycle is fundamental to interpreting haemodynamic data and understanding pathophysiology.

Systole

Isovolumic contraction: Begins with ventricular depolarisation (QRS complex) and subsequent ventricular contraction. Ventricular pressure exceeds atrial pressure, causing mitral and tricuspid valve closure (S1 heart sound). All four cardiac valves are closed during this brief period as ventricular pressure rises rapidly without volume change. Isovolumic contraction continues until ventricular pressure exceeds aortic and pulmonary arterial pressure, causing semilunar valve opening.

Ejection: When left ventricular pressure exceeds aortic pressure (typically 80-90 mmHg), the aortic valve opens. Blood is ejected rapidly during the rapid ejection phase as the pressure gradient between ventricle and aorta is maximal. Stroke volume is ejected during this phase. Reduced ejection follows as the pressure gradient narrows and the ventricle begins to relax. The dicrotic notch on the arterial waveform marks aortic valve closure as ventricular pressure falls below aortic pressure.

The systolic pressure-time index (SPTI), representing systolic myocardial oxygen demand, approximates the area under the systolic portion of the aortic pressure curve. This index correlates with myocardial oxygen consumption and is used to calculate the endocardial viability ratio.

Diastole

Isovolumic relaxation: Begins with aortic valve closure (S2 heart sound). All valves remain closed as ventricular pressure falls rapidly without volume change. This phase continues until ventricular pressure falls below atrial pressure, causing AV valve opening. The rate of pressure decline during isovolumic relaxation (dP/dt minimum) reflects ventricular relaxation and is an important determinant of diastolic function.

Rapid filling: Mitral valve opening causes rapid ventricular filling as blood flows down the pressure gradient from atrium to ventricle. This accounts for approximately 70% of ventricular filling in normal hearts. Early diastolic transmitral flow velocity (E wave) on Doppler echocardiography reflects this phase and is an important measure of diastolic function.

Diastasis: A period of slow filling when pressures equalise between atrium and ventricle. This phase is longest at slow heart rates and shortens or disappears at higher heart rates, compromising cardiac filling. The contribution of atrial contraction (atrial kick) becomes increasingly important when diastasis is abbreviated.

Atrial contraction: Atrial systole (P wave) adds 15-25% of ventricular filling in normal hearts. This contribution becomes critically important in diastolic dysfunction, hypertrophic cardiomyopathy, and tachycardia where the rapid filling phase is compromised. Loss of atrial contraction (atrial fibrillation) can reduce cardiac output by 15-30% in patients with diastolic dysfunction.

Timing Relationships

Systolic and diastolic intervals: At a heart rate of 75 beats per minute, the cardiac cycle is 800 ms. Systole occupies approximately 300 ms (38%) and diastole 500 ms (62%). As heart rate increases, diastole shortens disproportionately compared to systole. At 150 bpm, systole remains approximately 250 ms while diastole shortens to 150 ms. This explains why tachycardia particularly compromises coronary perfusion and ventricular filling.

Electromechanical delay: The interval between QRS onset and onset of pressure rise is approximately 40-50 ms, representing the time for depolarisation to spread and calcium release to trigger contraction. This delay accounts for the timing differences between electrical and mechanical events.

Systolic and diastolic time intervals: Measured via phonocardiography or invasive pressure monitoring. The pre-ejection period (PEP, from Q wave to aortic valve opening) and left ventricular ejection time (LVET, from aortic opening to closing) are systolic intervals. The PEP/LVET ratio increases with reduced contractility and is a non-invasive contractility index.

Pressure-Volume Loops

Pressure-volume loops provide a graphical representation of ventricular performance throughout the cardiac cycle, integrating pressure, volume, and time. They are fundamental to understanding preload, afterload, contractility, and their interrelationships.

Loop Components

End-diastolic point: The bottom-right point of the loop where filling is complete. Pressure equals left ventricular end-diastolic pressure (LVEDP, typically 5-12 mmHg) and volume equals end-diastolic volume (EDV, typically 120-130 mL). Changes in preload shift this point along the x-axis (volume axis).

Isovolumic contraction: The vertical line from the end-diastolic point to the aortic valve opening point. Pressure rises rapidly without volume change as all valves are closed. The slope of this line reflects contractility (dP/dt max).

Ejection phase: The curved upper border of the loop from aortic valve opening to closing. Volume decreases while pressure rises to a peak and then begins to fall. The area under this curve represents stroke work (pressure × volume). The width of the loop represents stroke volume.

End-systolic point: The upper-left point where ejection ends. Pressure equals left ventricular end-systolic pressure (LVESP, typically 100-120 mmHg) and volume equals end-systolic volume (ESV, typically 50-60 mL). Changes in afterload shift this point along the y-axis (pressure axis).

Isovolumic relaxation: The vertical line from end-systolic point to mitral valve opening. Pressure falls rapidly without volume change. The rate of pressure decline reflects diastolic relaxation (lusitropy).

Diastolic filling: The curved lower border from mitral valve opening to end-diastolic point. Volume increases while pressure rises gradually. The steepness of this curve reflects ventricular compliance.

Loop Analysis

Stroke volume: The horizontal width of the loop, calculated as EDV minus ESV. Normal stroke volume is 70-80 mL. Stroke volume increases with increased preload (Frank-Starling) or decreased afterload.

Ejection fraction: Stroke volume divided by EDV, expressed as percentage. Normal LVEF is 55-70%. Reduced ejection fraction indicates systolic dysfunction, while preserved EF with elevated filling pressures indicates diastolic dysfunction.

Stroke work: The area inside the pressure-volume loop, representing external work performed by the ventricle. Stroke work = ∫ P dV. Normal left ventricular stroke work is approximately 0.8-1.0 Joules per beat. Stroke work increases with increased preload, afterload, or contractility.

Pressure-volume area (PVA): The sum of stroke work area (loop area) and potential energy (triangular area between end-systolic pressure-volume relationship and loop). PVA correlates linearly with myocardial oxygen consumption. This relationship is fundamental to understanding the metabolic cost of cardiac work.

Ventricular Function Curves

End-systolic pressure-volume relationship (ESPVR): The line connecting end-systolic points from different loads. ESPVR slope (Ees, end-systolic elastance) is a load-independent index of contractility. Increased contractility shifts the ESPVR leftward (higher Ees), while decreased contractility shifts it rightward (lower Ees). Ees is relatively insensitive to preload but can be affected by afterload and heart rate.

End-diastolic pressure-volume relationship (EDPVR): The curve connecting end-diastolic points, representing ventricular compliance. The slope (dP/dV) increases exponentially with volume, reflecting decreasing compliance at high volumes. Reduced compliance (stiff ventricle) shifts the EDPVR upward and leftward. Compliance is affected by hypertrophy, ischaemia, fibrosis, and pericardial constraint.

Preload recruitable stroke work (PRSW): The linear relationship between stroke work and end-diastolic volume. PRSW slope is another load-independent contractility index that correlates with myocardial oxygen consumption. PRSW has advantages over Ees in that it doesn't require identification of true end-systole and is less sensitive to timing errors.

Frank-Starling Law

The Frank-Starling law (or Frank-Starling mechanism) describes the intrinsic ability of the heart to increase stroke volume in response to increased preload (ventricular filling). This fundamental principle explains how the heart matches output to venous return under normal physiological conditions.

Historical Context

Otto Frank (1895): Demonstrated the relationship between ventricular filling pressure and stroke volume in isolated frog hearts. Using the myograph, Frank showed that increased initial fibre length (preload) produced increased stroke work, establishing the length-tension relationship for cardiac muscle.

Ernest Starling (1914): Extended Frank's work in the isolated heart-lung preparation, demonstrating that increased right atrial pressure increased left ventricular stroke volume. Starling coined the term "law of the heart" and emphasised its physiological importance in matching ventricular output to venous return.

The Frank-Starling mechanism operates at the cellular level through the length-tension relationship of cardiac myocytes. Increased sarcomere length increases calcium sensitivity and the number of actin-myosin cross-bridges formed during contraction. The optimal sarcomere length for maximal tension development is approximately 2.2 μm, which corresponds to the physiological operating range of the ventricle.

Normal Operating Range

Physiological preload: In the normal heart, the Frank-Starling mechanism operates on the ascending limb of the length-tension curve. Small increases in end-diastolic volume produce significant increases in stroke volume, providing a mechanism for autoregulation of cardiac output. This explains how increases in venous return (exercise, fluid administration) are automatically matched by increased stroke volume.

Limits of the Frank-Starling mechanism: At very high filling pressures (greater than 20-25 mmHg), the ventricle operates on the plateau or descending limb of the curve. Further increases in preload produce diminishing returns or even reduced stroke volume as overdistension impairs contractility. This explains the clinical importance of avoiding excessive fluid administration in cardiac failure.

Diastolic dysfunction: In conditions with reduced ventricular compliance (hypertrophy, ischaemia, fibrosis), the EDPVR shifts upward, meaning that small increases in volume cause large increases in pressure. This places the ventricle further up on the Frank-Starling curve with less preload reserve, making the heart sensitive to volume changes.

Clinical Applications

Fluid responsiveness: The Frank-Starling mechanism predicts that fluid administration will increase cardiac output only if the patient is operating on the ascending limb of the curve. Patients on the plateau or descending limb will not respond or may deteriorate. Static measures of preload (CVP, PAOP) poorly predict fluid responsiveness. Dynamic measures (stroke volume variation, pulse pressure variation, passive leg raise) better predict responsiveness by testing the Frank-Starling mechanism.

Positive pressure ventilation: Increases intrathoracic pressure, reducing venous return and preload. In patients on the ascending limb of the Frank-Starling curve, this reduces cardiac output. This explains the hypotension seen with high PEEP and the importance of careful haemodynamic monitoring during mechanical ventilation.

Right ventricular function: The thin-walled RV is particularly preload-sensitive. Small decreases in venous return produce marked reductions in RV stroke volume. The RV is also afterload-sensitive because pulmonary vascular resistance is low and relatively small increases cause significant increases in RV afterload. RV failure can develop rapidly from either preload reduction (hypovolaemia) or afterload increase (pulmonary embolism, ARDS).

Exercise: Increases venous return through skeletal muscle pump and increased splanchnic vasoconstriction. The Frank-Starling mechanism contributes to the increase in stroke volume during submaximal exercise, though tachycardia and increased contractility become more important at higher workloads.

Coronary Perfusion

Coronary circulation presents unique physiological challenges because the heart must pump blood to itself against high intramural pressures. Understanding coronary perfusion physiology is essential for managing myocardial ischaemia, cardiac surgery, and critical illness.

Coronary Anatomy

Left coronary artery: Arises from the left coronary sinus, supplies the left ventricle, interventricular septum, and part of the right ventricle. Divides into the left anterior descending (LAD) artery supplying the anterior LV, anterior septum, and bundle of His, and the left circumflex artery supplying the lateral LV and left atrium. The left coronary supplies 70-80% of myocardial mass and has higher flow rates than the right coronary.

Right coronary artery: Arises from the right coronary sinus, supplies the right ventricle, inferior LV, posterior septum, SA node (60% of individuals), and AV node (90% of individuals). Right coronary dominance (present in 70-80% of population) means the RCA gives rise to the posterior descending artery. Left coronary dominance is present in 20-30%.

Coronary sinus: The main venous drainage of the heart, receiving blood from the great cardiac vein (LAD territory), middle cardiac vein (RCA territory), small cardiac vein (marginal branches), and posterior vein. The coronary sinus drains into the right atrium near the opening of the inferior vena cava. Coronary sinus blood has an oxygen saturation of 30-40%, reflecting the high myocardial oxygen extraction.

Coronary Blood Flow

Basal flow: Coronary blood flow at rest is 200-250 mL/min, representing 4-5% of cardiac output. This can increase 4-5 fold during maximal exercise (hyperaemic flow). Flow to the left coronary is higher than the right due to greater myocardial mass and higher work.

Phasic flow: Unlike other organs, coronary flow is highly phasic. Left coronary flow is predominantly diastolic (70-80%) because systolic intramural pressure compresses subendocardial vessels. Right coronary flow is more evenly distributed between systole and diastole because lower RV pressures cause less systolic compression. The DPTI/SPTI ratio (diastolic pressure-time index to systolic pressure-time index) reflects the balance between coronary supply (diastolic perfusion time) and demand (systolic work). Normal DPTI/SPTI is approximately 1.0.

Transmural distribution: Flow is higher to subendocardial layers compared to subepicardial layers because of higher metabolic demand and systolic compression reducing subendocardial flow. The endocardial/epicardial flow ratio at rest is 1.1-1.2:1. During tachycardia or ischaemia, this ratio decreases, making the subendocardium more vulnerable to ischaemia.

Coronary autoregulation: Coronary arteries maintain constant flow over a wide range of perfusion pressures (60-140 mmHg). Autoregulation involves metabolic, myogenic, and endothelial mechanisms. Metabolic factors (adenosine, CO₂, H⁺, lactate) are the primary regulators, increasing vasodilation when oxygen demand increases or supply decreases. The coronary flow reserve (ratio of hyperaemic to basal flow) is 4-5:1 in normal vessels and is reduced in coronary artery disease.

Determinants of Coronary Perfusion

Coronary perfusion pressure: The driving pressure for coronary flow, calculated as aortic diastolic pressure minus LVEDP (for the left coronary). Normal CPP is 60-80 mmHg. When CPP falls below 50-60 mmHg, autoregulatory capacity is exceeded and flow becomes pressure-dependent. This explains the importance of maintaining adequate diastolic pressure in patients with coronary artery disease.

Diastolic time: Since most left coronary flow occurs during diastole, the duration of diastole is critical. Tachycardia reduces diastolic time disproportionately, reducing coronary perfusion time. For a heart rate of 150 bpm, diastole may be only 100-150 ms per cycle, severely limiting coronary flow. This explains why tachycardia can precipitate ischaemia even in normal coronary arteries.

Intramural pressure: The pressure within the myocardium, determined by ventricular pressure during systole and tissue pressure during diastole. High intramural pressure compresses intramyocardial vessels, reducing flow. This is particularly important during systole and in conditions of high ventricular pressure (hypertension, aortic stenosis, hypertrophic cardiomyopathy). Subendocardial vessels experience the highest intramural pressure, explaining their vulnerability.

Coronary vascular resistance: Determined by vascular tone and structural factors. Vascular tone is regulated by metabolic demand (adenosine, CO₂), endothelial factors (NO, endothelin), and autonomic innervation (sympathetic alpha-mediated vasoconstriction, beta-mediated vasodilation). Structural factors include atherosclerosis, vascular remodeling, and extravascular compression from hypertrophy or fibrosis.

Clinical Implications

Coronary artery disease: Reduces hyperaemic flow reserve even at rest. Flow may be adequate at rest but cannot increase adequately during demand, causing demand ischaemia. Critical stenosis (greater than 70% diameter) produces resting flow limitation. The coronary steal phenomenon describes redistribution of flow from ischaemic to normal territories when vasodilators (adenosine, dipyridamole) are administered.

Cardiac surgery: Cardioplegia must arrest the heart and provide myocardial protection during aortic cross-clamping. Warm or cold blood cardioplegia, antegrade or retrograde delivery, and intermittent dosing aim to maintain myocardial viability. The importance of coronary sinus drainage explains the use of retrograde cardioplegia delivery in complex procedures.

Shock states: In cardiogenic shock, reduced cardiac output and hypotension compromise coronary perfusion, creating a vicious cycle. Inotropic support improves cardiac output and coronary perfusion. In distributive shock (septic), coronary flow may be preserved despite hypotension due to vasodilation, but impaired oxygen utilisation and myocardial depression can still cause ischaemia.

Ventilation: Positive pressure ventilation reduces venous return and cardiac output, potentially reducing coronary perfusion. High PEEP increases intrathoracic pressure, reducing arterial diastolic pressure and potentially coronary perfusion pressure. These effects are most pronounced in hypovolaemic patients and those with right ventricular failure.

Myocardial Oxygen Demand and Consumption

The myocardium extracts 70-80% of oxygen from arterial blood, the highest of any organ. Increased oxygen demand must be met by increased coronary blood flow rather than increased extraction, making coronary flow regulation critical. Understanding myocardial oxygen consumption is essential for managing ischaemia, cardiac surgery, and critical illness.

Determinants of Myocardial Oxygen Consumption

Heart rate: The most important determinant of MVO₂ under most physiological conditions. MVO₂ increases approximately linearly with heart rate because each heartbeat requires activation of actin-myosin cross-bridges and calcium cycling. The oxygen cost of each beat (oxygen pulse) is relatively constant, so total oxygen consumption = HR × oxygen pulse. This explains why tachycardia can precipitate ischaemia even when other factors are normal.

Contractility: The second major determinant of MVO₂. Increased contractility increases ATP consumption for cross-bridge cycling and calcium handling. Catecholamines increase MVO₂ both through increased contractility and increased heart rate. Drugs that increase contractility without increasing heart rate (e.g., levosimendan) have a more favourable oxygen cost profile.

Wall tension: According to the law of Laplace (T = P × r / 2h), wall tension increases with increased pressure, radius, and decreased wall thickness. Tension is a major determinant of oxygen consumption because tension generation requires actin-myosin interaction. This explains the high oxygen demand of pressure overload (aortic stenosis, hypertension) and volume overload (regurgitation).

Pressure-volume area (PVA): A comprehensive index of ventricular work that predicts MVO₂. PVA is the sum of external stroke work (area inside the PV loop) and potential energy (triangular area between ESPVR and loop). The relationship between MVO₂ and PVA is linear: MVO₂ = a × PVA + b, where 'a' represents the oxygen cost of external work and 'b' represents basal metabolism (unloaded MVO₂). This relationship provides a mechanistic understanding of oxygen consumption.

Basal metabolism: Approximately 15-20% of total MVO₂ at rest, representing energy for ion transport, protein synthesis, and cellular maintenance. Basal metabolism cannot be reduced and is constant across a wide range of conditions. This explains why cardiac arrest with zero external work still consumes oxygen for cellular integrity.

Clinical Measurements

Systolic pressure-time index (SPTI): The area under the systolic portion of the aortic pressure curve, representing systolic myocardial oxygen demand. SPTI increases with increased pressure or systolic duration (prolonged ejection, tachycardia). SPTI is used in the endocardial viability ratio (EVR = DPTI/SPTI) to assess subendocardial oxygen balance.

Diastolic pressure-time index (DPTI): The area under the diastolic aortic pressure curve minus LVEDP, representing diastolic coronary perfusion and oxygen supply. DPTI decreases with decreased diastolic pressure or shortened diastole (tachycardia). The EVR (normally greater than 1.0) decreases when demand exceeds supply, predicting subendocardial ischaemia.

Rate-pressure product (RPP): Heart rate × systolic blood pressure, a clinical estimate of myocardial oxygen demand. RPP correlates reasonably well with MVO₂ (r ≈ 0.85) and is useful for titrating beta-blockers and monitoring myocardial stress. Normal RPP at rest is approximately 8,000-10,000, can increase to 20,000-30,000 during exercise.

Tension-time index (TTI): Systolic pressure × systolic time, another estimate of oxygen demand. TTI incorporates both pressure and the duration of systole, making it more sensitive to prolonged ejection (e.g., aortic stenosis) than RPP.

Pathophysiological States

Ischaemia: Reduced oxygen supply relative to demand. Demand ischaemia occurs when demand increases without increased supply (tachycardia, hypertension, stress). Supply ischaemia occurs when supply is reduced (coronary stenosis, hypotension, anaemia, carboxyhaemoglobin). Ischaemia rapidly shifts metabolism from aerobic to anaerobic, causing lactate production, contractile dysfunction, and ECG changes.

Hibernating myocardium: Chronic hypoperfusion causing reversible contractile dysfunction without necrosis. Myocardium downregulates contractility to match reduced oxygen supply, preserving cellular integrity. Revascularisation can restore function. Hibernating myocardium is metabolically active (glucose uptake) but with reduced blood flow.

Stunned myocardium: Post-ischaemic dysfunction despite restored perfusion. Prolonged ischaemia causes calcium overload, free radical damage, and contractile protein dysfunction. Function recovers over days to weeks without intervention. Stunned myocardium has normal perfusion but reduced contractility.

Reperfusion injury: Damage occurring when blood flow is restored after ischaemia. Mechanisms include calcium overload, oxygen free radicals, neutrophil activation, and mitochondrial permeability transition. Reperfusion can cause arrhythmias, microvascular obstruction (no-reflow), and accelerated cell death despite restored flow. Therapeutic hypothermia, postconditioning, and antioxidant strategies aim to limit reperfusion injury.

Therapeutic Implications

Beta-blockers: Reduce MVO₂ primarily by reducing heart rate and contractility. The reduction in heart rate is more important than the reduction in contractility because heart rate is the major determinant. Beta-blockers also prolong diastole, improving coronary perfusion time. These effects make beta-blockers essential in chronic coronary artery disease and acute coronary syndromes.

Calcium channel blockers: Reduce MVO₂ by reducing afterload (vasodilation) and contractility (non-dihydropyridines). Heart rate may increase (dihydropyridines) or decrease (verapamil, diltiazem). The net effect is reduced oxygen demand, beneficial in coronary artery disease. Verapamil and diltiazem also improve diastolic relaxation, beneficial in diastolic dysfunction.

Nitrates: Reduce preload (venodilation) and afterload (arterial vasodilation). The reduction in preload and ventricular volume reduces wall tension and oxygen demand according to Laplace's law. Nitrates also directly dilate epicardial coronary arteries and improve collateral flow. The reduction in preload must be balanced against potential hypotension and reduced coronary perfusion pressure.

ACE inhibitors: Reduce afterload by reducing systemic vascular resistance, decreasing wall tension and oxygen demand. They also reduce ventricular remodelling after myocardial infarction, preventing progressive dilation and increased wall stress. Long-term use reduces cardiovascular mortality in patients with ventricular dysfunction or coronary disease.

Inotropes: Increase oxygen demand by increasing contractility and heart rate. This can worsen ischaemia in patients with coronary artery disease. Dobutamine increases contractility and heart rate, significantly increasing MVO₂. Milrinone increases contractility with less tachycardia but still increases MVO₂. Levosimendan increases contractility without increasing MVO₂ as much, possibly beneficial in acute decompensated heart failure with ischaemia.

Autonomic Nervous System

The autonomic nervous system provides beat-to-beat regulation of cardiovascular function through sympathetic and parasympathetic pathways. Understanding autonomic control is essential for interpreting haemodynamic responses to stress, drugs, and disease.

Sympathetic Nervous System

Anatomy: Preganglionic sympathetic neurons originate in the intermediolateral cell column of the spinal cord (T1-L2). Fibres synapse in paravertebral or prevertebral ganglia before innervating the heart. Postganglionic fibres release norepinephrine at cardiac nerve terminals and epinephrine from the adrenal medulla.

Receptors: Alpha₁ receptors mediate vasoconstriction in vascular smooth muscle. Alpha₂ receptors inhibit norepinephrine release (presynaptic) and cause venoconstriction (postsynaptic). Beta₁ receptors increase heart rate (chronotropy), contractility (inotropy), relaxation rate (lusitropy), and conduction velocity (dromotropy). Beta₂ receptors cause vasodilation in skeletal muscle and bronchial smooth muscle.

Effects on the heart: Sympathetic stimulation via norepinephrine increases heart rate through SA node acceleration (beta₁). Positive inotropy results from increased calcium entry during the action potential and increased calcium release from the sarcoplasmic reticulum. Positive lusitropy (enhanced relaxation) results from faster calcium reuptake by SERCA. Conduction velocity increases in the AV node and His-Purkinje system, reducing PR and QRS intervals.

Effects on vasculature: Sympathetic stimulation causes alpha-mediated vasoconstriction in skin, splanchnic, and renal vessels, redirecting blood flow to skeletal muscle and brain. Skeletal muscle vessels dilate via beta₂ receptors during intense sympathetic activation (exercise). Venous constriction increases venous return and preload. Net effect is increased systemic vascular resistance.

Baroreceptor reflex: Baroreceptor firing inhibits sympathetic outflow from the vasomotor centre. Decreased baroreceptor firing (hypotension) disinhibits sympathetic outflow, increasing heart rate, contractility, and vascular resistance. This reflex operates on timescales of seconds to minutes.

Chemoreceptor reflex: Peripheral chemoreceptors (carotid and aortic bodies) respond to hypoxia, hypercapnia, and acidosis. Hypoxia causes hyperventilation and sympathetic activation, increasing cardiac output. Hypercapnia causes hyperventilation and variable sympathetic effects depending on PaCO₂ level.

Parasympathetic Nervous System

Anatomy: Preganglionic parasympathetic neurons originate in the nucleus ambiguus and dorsal motor nucleus of the vagus. Fibres travel in the vagus nerve to intracardiac ganglia near the SA and AV nodes. Postganglionic fibres are short and release acetylcholine.

Receptors: Muscarinic (M₂) receptors on cardiac myocytes mediate parasympathetic effects. Vagal stimulation opens acetylcholine-sensitive potassium channels (IKACh), hyperpolarising the SA node and decreasing heart rate.

Effects on the heart: Parasympathetic stimulation via the vagus nerve decreases heart rate (negative chronotropy) by reducing SA node automaticity. AV nodal conduction velocity and refractory period increase, causing PR interval prolongation. Parasympathetic effects are minimal on ventricular myocytes (minimal direct negative inotropy) but reduce contractility indirectly through decreased heart rate.

Respiratory sinus arrhythmia: The normal variation in heart rate with respiration, increasing during inspiration (decreased vagal tone) and decreasing during expiration (increased vagal tone). RSA is a marker of vagal tone and parasympathetic function. RSA is prominent in healthy young adults and decreases with age and autonomic dysfunction.

Baroreceptor reflex: Baroreceptor firing stimulates parasympathetic outflow from the nucleus ambiguus. Increased baroreceptor firing (hypertension) increases vagal tone, decreasing heart rate. This reflex is the primary mechanism for rapid heart rate control in response to blood pressure changes.

Autonomic Balance

Vagal tone: Dominant parasympathetic influence at rest, maintaining slow heart rates and high HRV. High vagal tone is protective against arrhythmias and associated with favourable prognosis. Vagal tone decreases with age, sedation, heart failure, and critical illness.

Sympathetic activation: Dominant during stress (exercise, haemorrhage, sepsis, surgery). Sympathetic activation increases heart rate, contractility, and vascular resistance to maintain cardiac output and blood pressure. Chronic sympathetic activation (heart failure, hypertension) is maladaptive, causing arrhythmias, myocardial necrosis, and adverse remodelling.

Autonomic nervous system dysfunction: Common in critical illness. Autonomic dysfunction in sepsis includes reduced heart rate variability, impaired baroreflex sensitivity, and sympathetic overactivity. This correlates with severity and prognosis. Autonomic dysfunction in heart failure includes increased sympathetic activity and decreased parasympathetic tone, contributing to arrhythmias and progression.

Pharmacological Modulation

Sympathomimetic drugs: Epinephrine activates alpha, beta₁, and beta₂ receptors, causing tachycardia, hypertension, and bronchodilation. Norepinephrine activates alpha and beta₁ receptors, causing hypertension with reflex bradycardia (strong alpha effect). Dopamine activates dopaminergic receptors at low doses (renal vasodilation), beta₁ at moderate doses, and alpha at high doses. Dobutamine primarily activates beta₁ receptors, increasing contractility and heart rate.

Parasympathomimetic drugs: Acetylcholine agonists (bethanechol) are rarely used clinically. Cholinesterase inhibitors (neostigmine, pyridostigmine) increase endogenous acetylcholine, causing bradycardia and increased secretions. Used as reversal agents for neuromuscular blockade.

Sympatholytic drugs: Beta-blockers inhibit sympathetic stimulation at beta receptors, reducing heart rate, contractility, and blood pressure. Alpha-blockers inhibit vasoconstriction, causing vasodilation. Centrally acting sympatholytics (clonidine) reduce sympathetic outflow from the vasomotor centre.

Parasympatholytic drugs: Atropine and scopolamine block muscarinic receptors, causing tachycardia, decreased secretions, and mydriasis. Atropine is used for bradycardia and as premedication. Atropine is ineffective in heart transplant recipients because the vagus nerve is sectioned.

Baroreceptor Reflexes

Baroreceptor reflexes provide rapid blood pressure regulation through negative feedback, operating on timescales of seconds to minutes. Understanding baroreflex physiology is essential for interpreting haemodynamic responses to position changes, medications, and disease.

Baroreceptor Anatomy

Carotid sinus baroreceptors: Located at the bifurcation of the common carotid artery, innervated by the glossopharyngeal nerve (CN IX). The carotid sinus is a specialised area of the arterial wall with increased compliance and high receptor density. Carotid sinus massage (Czermak-Hering manoeuvre) stimulates these receptors, used to terminate supraventricular tachycardia.

Aortic arch baroreceptors: Located in the aortic arch, innervated by the vagus nerve (CN X). Aortic baroreceptors have higher discharge frequencies than carotid baroreceptors at equivalent pressures, providing different pressure sensitivities.

Receptor characteristics: Baroreceptors are stretch-sensitive nerve endings in the adventitia of the arterial wall. Discharge frequency increases with increased arterial pressure and stretch. Baroreceptors adapt rapidly (phasic component) and slowly (tonic component) to sustained pressure changes. The phasic component responds to pulse pressure, while the tonic component responds to mean pressure.

Operational range: Baroreceptors respond to pressures from approximately 60-180 mmHg. Below 60 mmHg, discharge is minimal. Above 180 mmHg, discharge is maximal with no further increase. Maximum sensitivity (steepest pressure-response curve) is around 100-120 mmHg, close to normal blood pressure.

Baroreflex Pathway

Afferent limb: Baroreceptor firing signals travel via the glossopharyngeal nerve (carotid sinus) and vagus nerve (aortic arch) to the nucleus tractus solitarius (NTS) in the medulla. The NTS integrates baroreceptor signals and projects to other medullary centres.

Central integration: The NTS projects to the caudal ventrolateral medulla (CVLM), which contains inhibitory interneurons. The CVLM inhibits the rostral ventrolateral medulla (RVLM), which contains sympathetic preganglionic neurons. Baroreceptor activation (increased pressure) increases NTS activity, which increases CVLM activity, which inhibits RVLM, reducing sympathetic outflow. The NTS also projects to the nucleus ambiguus (parasympathetic motor neurons).

Efferent limb: Decreased RVLM activity reduces sympathetic outflow, decreasing heart rate, contractility, and vascular resistance. Increased nucleus ambiguus activity increases vagal outflow, decreasing heart rate and AV nodal conduction. The net effect is decreased cardiac output and blood pressure.

Feedback loop: Baroreceptor firing inhibits sympathetic and stimulates parasympathetic outflow. Decreased baroreceptor firing (hypotension) disinhibits sympathetic and inhibits parasympathetic outflow. This negative feedback loop stabilises blood pressure around a set point.

Baroreflex Sensitivity

Baroreflex sensitivity (BRS): The change in heart rate (or R-R interval) per unit change in blood pressure, typically expressed as ms/mmHg. BRS is measured by pharmacological methods (phenylephrine or nitroprusside infusion) or spontaneous methods (sequence method, spectral analysis). Normal BRS is 10-20 ms/mmHg in young adults, decreasing with age and cardiovascular disease.

Factors affecting BRS: Age (decreases with age), hypertension (decreased due to arterial stiffness), heart failure (decreased), myocardial infarction (decreased, especially with LV dysfunction), diabetes (autonomic neuropathy), and medications (beta-blockers decrease BRS, ACE inhibitors increase BRS). High BRS is protective against arrhythmias and sudden cardiac death.

Respiratory modulation: Baroreflex sensitivity is higher during expiration than inspiration. Respiratory sinus arrhythmia results from respiratory modulation of vagal outflow. Deep breathing tests BRS by using the maximal heart rate change with respiration.

Clinical significance: Decreased BRS is an independent predictor of mortality after myocardial infarction. BRS is used to assess autonomic function and prognosis in various conditions. Reduced BRS in heart failure, myocardial infarction, and diabetes indicates autonomic dysfunction.

Baroreceptor Resetting

Acute resetting: Baroreceptors rapidly adapt to sustained changes in blood pressure, shifting their operational range. A sudden increase in blood pressure causes an initial increase in baroreceptor firing followed by rapid adaptation over minutes to hours, maintaining sensitivity around the new pressure. This allows baroreceptors to respond to changes around the prevailing pressure.

Chronic resetting: In chronic hypertension, baroreceptors adapt to higher operating pressures over days to weeks. The baroreflex curve shifts rightward, defending the elevated blood pressure. This explains why chronic hypertensive patients have symptoms of hypotension at blood pressures that would be normal in normotensive individuals.

Hypotensive resetting: Chronic hypotension (e.g., heart failure) causes leftward shift of the baroreflex curve. The baroreceptors become more sensitive to maintain blood pressure at lower levels. This explains the tachycardia seen in chronic heart failure despite low blood pressure.

Clinical Implications

Orthostatic hypotension: Gravitational pooling of blood in the legs reduces venous return and cardiac output upon standing. Baroreceptors detect decreased pressure, increasing sympathetic and decreasing parasympathetic outflow. This increases heart rate and vasoconstriction, restoring blood pressure. Impaired baroreflex causes orthostatic hypotension, seen in autonomic neuropathy, medications, and ageing.

Carotid sinus hypersensitivity: Exaggerated baroreceptor response causing bradycardia or hypotension with carotid sinus stimulation. Cardioinhibitory type causes asystole greater than 3 seconds. Vasodepressor type causes SBP drop greater than 50 mmHg. Mixed type has both components. Presents as syncope or presyncope. Treatment includes pacemaker for cardioinhibitory type and medications for vasodepressor type.

Postural tachycardia syndrome (POTS): Inappropriate tachycardia (greater than 30 bpm increase) upon standing without hypotension. Mechanism includes hypovolaemia, autonomic dysfunction, and hyperadrenergic state. Baroreflex function may be abnormal. Treatment includes volume expansion, compression stockings, and medications (beta-blockers, fludrocortisone, midodrine).

Baroreflex activation therapy: Electrical stimulation of carotid sinus to activate baroreceptors, treating resistant hypertension. Reduces sympathetic outflow and blood pressure. Approved for treatment-resistant hypertension not controlled by maximally tolerated medications.

Critical illness: Baroreflex function is impaired in sepsis, trauma, and critical illness. Reduced BRS correlates with organ dysfunction and mortality. Sedation and medications also affect baroreflex function. Monitoring heart rate variability provides information on baroreflex function and prognosis.

Determinants of Mean Arterial Pressure

Mean arterial pressure (MAP) is the driving pressure for organ perfusion and is determined by the interaction of cardiac output and systemic vascular resistance. Understanding the determinants of MAP is fundamental to haemodynamic management in intensive care.

Fundamental Equation

MAP = CO × SVR: Mean arterial pressure equals cardiac output multiplied by systemic vascular resistance. This is derived from the relationship Q = ΔP/R, where Q is flow (CO), ΔP is pressure gradient (MAP - CVP ≈ MAP), and R is resistance (SVR). This equation explains the two fundamental approaches to blood pressure management: increasing CO (inotropes, fluids) or increasing SVR (vasopressors).

Cardiac output: Stroke volume × heart rate. Normal CO is 4-8 L/min. CO varies with metabolic demand, increasing 2-4 fold during exercise. CO is influenced by preload (Frank-Starling), afterload, contractility, and heart rate. CO can be measured by thermodilution (pulmonary artery catheter), pulse contour analysis (PiCCO, LiDCO), or echocardiography.

Systemic vascular resistance: Afterload opposing left ventricular ejection. Normal SVR is 800-1200 dyn·s·cm⁻⁵. SVR is determined by vascular tone (arteriolar constriction/dilation), blood viscosity, and vessel length. SVR is calculated as SVR = 80 × (MAP - CVP) / CO. Increased SVR increases blood pressure but may reduce organ perfusion if excessive.

Mean arterial pressure calculation: MAP ≈ DBP + 1/3 PP, where DBP is diastolic blood pressure and PP is pulse pressure (SBP - DBP). This formula reflects the fact that diastole occupies approximately 2/3 of the cardiac cycle at normal heart rates. More accurate calculations incorporate heart rate: MAP = DBP + PP / (1 + ejection fraction × HR/100). Normal MAP is 70-100 mmHg.

Autoregulation

Definition: The ability of organs to maintain constant blood flow over a wide range of perfusion pressures. Autoregulation occurs through metabolic, myogenic, and endothelial mechanisms. Myogenic mechanisms involve vascular smooth muscle contraction in response to stretch. Metabolic mechanisms involve vasodilation in response to increased metabolic demand (adenosine, CO₂, H⁺). Endothelial mechanisms involve NO and endothelin release.

Cerebral autoregulation: Maintains constant cerebral blood flow (CBF ≈ 50 mL/100g/min) over MAP 60-150 mmHg. Below 60 mmHg, CBF decreases linearly with pressure, causing cerebral ischaemia. Above 150 mmHg, CBF increases (breakthrough), risking hyperperfusion and cerebral oedema. Autoregulation is impaired in traumatic brain injury, stroke, and chronic hypertension (rightward shift).

Renal autoregulation: Maintains constant glomerular filtration rate (GFR) over MAP 80-180 mmHg. Mediated by tubuloglomerular feedback (macula densa senses NaCl delivery) and myogenic mechanism of afferent arterioles. Impaired autoregulation contributes to hypertension and progressive kidney disease.

Coronary autoregulation: Maintains constant coronary flow over MAP 60-140 mmHg. Coronary flow reserve (ratio of hyperaemic to basal flow) is 4-5:1 in normal vessels, reduced in coronary artery disease. Autoregulation shifts rightward in chronic hypertension, making the heart more vulnerable to hypotension.

Critical closing pressure: The pressure at which blood flow ceases due to vascular collapse. In most tissues, critical closing pressure is 10-20 mmHg. In the brain, it may be 30-40 mmHg. When MAP approaches critical closing pressure, flow becomes pressure-dependent and organ ischaemia develops. This explains the importance of maintaining adequate MAP in shock states.

Distribution of Cardiac Output

Normal distribution: At rest, cardiac output is distributed as follows: brain 13-15%, heart 4-5%, kidneys 20-25%, splanchnic organs 25-30%, skeletal muscle 20-25%, skin 5-10%, other organs below 5%. This distribution changes dramatically during stress.

Exercise redistribution: During maximal exercise, skeletal muscle receives up to 80% of cardiac output. Splanchnic and renal vasoconstriction redirects blood to working muscle. Coronary flow increases 3-4 fold. Cerebral flow is maintained constant through autoregulation.

Shock redistribution: In cardiogenic shock, vasoconstriction maintains MAP but compromises splanchnic, renal, and cutaneous perfusion to preserve cerebral and coronary flow. In distributive shock (septic), vasodilation causes maldistribution, with shunting, impaired oxygen extraction, and tissue hypoxia despite normal or increased flow.

Pressure-Flow Relationships

Ohm's law analogue: MAP = CO × SVR, analogous to V = I × R. This relationship is useful conceptually but is an oversimplification. The cardiovascular system is non-linear, with SVR varying with CO, pressure, and flow. Vascular compliance causes differences between steady-state and pulsatile flow.

Venous return: The flow returning to the right atrium, driven by the pressure gradient between peripheral tissues and right atrium. Mean systemic filling pressure (MSFP) is the equilibrium pressure in the circulation when flow is zero (approximately 7-10 mmHg). Venous return = (MSFP - RAP) / VRresistance, where RAP is right atrial pressure. This equation complements CO determination and explains how reduced RAP (e.g., hypovolaemia) reduces venous return and CO.

Guyton's venous return curve: The relationship between venous return and right atrial pressure. As RAP decreases, venous return increases until it plateaus at negative pressures (vascular collapse). The intersection of the venous return curve and cardiac function curve determines the steady-state CO and RAP. This framework explains the interdependence of CO, venous return, and right heart function.

Clinical Applications

Hypotension management: Hypotension can result from decreased CO (cardiogenic, hypovolaemic shock) or decreased SVR (distributive shock). Therapeutic approach depends on underlying mechanism. Cardiogenic shock: inotropes, consider vasodilators if SVR is high. Hypovolaemic shock: fluid resuscitation. Distributive shock: vasopressors to increase SVR, consider inotropes if CO is inadequate.

Vasopressors: Increase MAP by increasing SVR. Norepinephrine increases SVR with modest cardiac effects (some beta₁). Phenylephrine increases SVR purely via alpha₁ effects. Vasopressin acts via V₁ receptors, increasing SVR. Vasopressors maintain perfusion pressure but may reduce organ flow if excessive vasoconstriction occurs.

Inotropes: Increase CO primarily, which may increase MAP if SVR is unchanged or decreased. Dobutamine increases CO but may decrease MAP due to vasodilation. Milrinone increases CO with vasodilation. Inotropes are used when CO is inadequate despite adequate MAP or when low CO causes organ dysfunction.

Fluids: Increase CO via increased preload (Frank-Starling). Effect on MAP depends on the position on the Frank-Starling curve. Patients on the ascending limb will increase CO and MAP. Patients on the plateau will not increase CO and may develop pulmonary oedema. Fluid responsiveness testing is essential.

Target MAP: Recommended MAP targets vary by condition. Normal individuals: greater than 65 mmHg. Chronic hypertension: may need higher MAP (greater than 80-100 mmHg) due to rightward-shifted autoregulation. Sepsis: 65 mmHg vs higher targets trial showed no mortality benefit for higher MAP (≥85 mmHg), but higher MAP may benefit patients with chronic hypertension (PMID: 25049333). Traumatic brain injury: ≥80 mmHg to maintain cerebral perfusion pressure.

Clinical Applications and Assessment

Cardiovascular physiology principles guide clinical decision-making in intensive care, including haemodynamic monitoring, vasoactive drug selection, and management of shock states.

Haemodynamic Monitoring

Arterial line: Provides continuous blood pressure monitoring and arterial blood gas sampling. Allows calculation of MAP, pulse pressure, and systolic pressure variation. MAP is the critical parameter for organ perfusion. Damping coefficient and natural frequency affect waveform fidelity.

Central venous pressure: Measures right atrial pressure, influenced by blood volume, cardiac function, and intrathoracic pressure. CVP is a poor predictor of fluid responsiveness but indicates right heart filling pressures and venous congestion. Normal CVP is 0-8 mmHg. CVP trends are more useful than absolute values.

Pulmonary artery catheter: Provides CO (thermodilution), PAOP (left heart filling pressure), PAP (pulmonary artery pressure), and mixed venous oxygen saturation (SvO₂). PAOP estimates LVEDP but is affected by lung compliance and PEEP. CO measurement guides inotrope and fluid therapy. SvO₂ reflects the balance between oxygen delivery and consumption.

Echocardiography: Non-invasive assessment of cardiac structure and function. Provides estimates of LVEF, diastolic function, valve function, and volume status. Doppler measurements of transmitral flow and tissue Doppler assess diastolic function. Strain imaging detects early systolic dysfunction. Point-of-care echocardiography is increasingly used in ICU.

Shock States

Cardiogenic shock: Primary pump failure, characterised by low CO and high SVR. MAP may be low, normal, or high depending on sympathetic compensation. Treatment includes inotropes (dobutamine, milrinone, norepinephrine) to increase CO, consider vasodilators (nitroprusside) if SVR is very high and MAP is adequate, and mechanical circulatory support (IABP, VA-ECMO) for refractory cases. IABP reduces afterload and improves coronary perfusion but does not improve mortality (IABP-SHOCK II trial, PMID: 23022488).

Hypovolaemic shock: Reduced intravascular volume, characterised by low CO and high SVR (vasoconstriction). Treatment is fluid resuscitation. Fluid responsiveness testing (stroke volume variation, pulse pressure variation, passive leg raise) guides therapy. Crystalloids are first-line, with colloids or blood products for specific indications. Goal-directed therapy using stroke volume optimisation improves outcomes in high-risk surgery (PMID: 20194949).

Distributive shock (septic): Systemic vasodilation with increased or normal CO, characterised by high CO and low SVR. Treatment includes vasopressors to increase SVR (norepinephrine first-line), consider vasopressin as second-line. Inotropes (dobutamine) added if CO is low or ScvO₂ below 70%. Source control and antibiotics are essential. Early goal-directed therapy (Rivers protocol) showed benefit in initial study (PMID: 11794169) but not confirmed in subsequent trials (ProCESS, ARISE, PROMISE).

Obstructive shock: Mechanical obstruction to cardiac output, characterised by low CO and high SVR. Causes include pulmonary embolism (increased RV afterload), cardiac tamponade (impaired filling), tension pneumothorax (impaired venous return). Treatment addresses the obstruction: thrombolysis or embolectomy for PE, pericardiocentesis for tamponade, needle decompression for pneumothorax. Inotropes and vasopressors provide temporary support while definitive treatment is administered.

Critical Care Pharmacology

Catecholamines: Norepinephrine is first-line vasopressor for most shock states (alpha > beta₁). Epinephrine causes tachycardia and increased myocardial oxygen consumption, used in cardiac arrest and anaphylaxis. Dopamine increases renal blood flow at low doses but is not superior to norepinephrine in septic shock (SOAP II trial, PMID: 20472416). Dobutamine is a positive inotrope with some vasodilation.

Non-catecholamine inotropes: Milrinone (phosphodiesterase-3 inhibitor) increases cAMP, producing inotropy and vasodilation. Benefits include reduced pulmonary vascular pressure and less tachycardia than catecholamines. Levosimendan (calcium sensitiser) increases contractility by stabilising troponin C, may have benefits in acute decompensated heart failure but does not reduce mortality (SURVIVE trial, PMID: 19141615).

Vasopressors: Vasopressin acts via V₁ receptors, causes vasoconstriction, and preserves renal blood flow better than norepinephrine. Used as second-line in septic shock (VASST trial, PMID: 18376085). Phenylephrine is a pure alpha₁ agonist, increases SVR without increasing heart rate, useful in patients with tachyarrhythmias.

Beta-blockers: Propranolol (non-selective), metoprolol (beta₁ selective), atenolol (beta₁ selective), esmolol (short-acting). Used to control heart rate in AF, reduce myocardial oxygen demand in coronary disease, and treat heart failure (carvedilol, bisoprolol, metoprolol succinate). Contraindicated in acute decompensated heart failure, cardiogenic shock, and severe bradycardia.

Calcium channel blockers: Verapamil and diltiazem (non-dihydropyridines) cause negative inotropy, chronotropy, and afterload reduction. Used for rate control in AF, angina, and hypertrophic cardiomyopathy. Dihydropyridines (amlodipine, nifedipine) cause vasodilation with minimal cardiac effects, used for hypertension and angina.

SAQ Practice Questions

SAQ 1: Cardiac Cycle and Pressure-Volume Relationships (15 marks)

Question: A 68-year-old male with a history of hypertension and ischaemic heart disease develops acute decompensated heart failure. Echocardiography shows left ventricular ejection fraction 35%, severe mitral regurgitation, and elevated left atrial pressure.

a) Describe the phases of the cardiac cycle and the corresponding pressure-volume changes. (6 marks)

b) Draw and label a pressure-volume loop for this patient's left ventricle. Explain how it differs from a normal loop. (5 marks)

c) Explain how the Frank-Starling mechanism contributes to compensatory increases in stroke volume in this patient, and why this compensation is limited. (4 marks)

Model Answer:

a) Phases of the cardiac cycle (6 marks):

Isovolumic contraction: Begins with mitral valve closure (S1). Ventricular pressure rises rapidly from LVEDP to aortic diastolic pressure (80-90 mmHg). All valves closed. Duration ~50-80 ms. Reflects isovolumic contraction and early systolic pressure development.
Rapid ejection: Begins with aortic valve opening. Blood ejected rapidly as ventricular pressure exceeds aortic pressure. Pressure rises to peak (~120-130 mmHg) then begins to fall. Volume decreases rapidly. Accounts for ~60% of stroke volume.
Reduced ejection: Pressure gradient between ventricle and aorta narrows. Ejection slows. Pressure falls toward aortic diastolic pressure. Aortic valve closes when ventricular pressure falls below aortic pressure (dicrotic notch).
Isovolumic relaxation: Begins with aortic valve closure (S2). All valves closed. Ventricular pressure falls rapidly from LVESP to left atrial pressure. Duration ~50-100 ms. Reflects active relaxation (lusitropy).
Rapid filling: Mitral valve opens. Blood flows rapidly from atrium to ventricle down pressure gradient. Accounts for ~70% of ventricular filling. Early diastolic transmitral flow (E wave).
Diastasis: Period of slow filling as pressures equalise. Duration varies inversely with heart rate (shortens or absent at high HR).
Atrial contraction: Atrial systole adds 15-25% of ventricular filling. Particularly important when diastolic filling is compromised (diastolic dysfunction, tachycardia).

b) Pressure-volume loop for reduced EF (5 marks):

Key differences from normal loop:

Wider loop (larger ESV): End-systolic volume increased significantly due to reduced contractility (e.g., ESV 100 mL vs normal 50-60 mL)
Shifted ESPVR rightward: End-systolic pressure-volume relationship slope (Ees) decreased, indicating reduced contractility
Shifted EDPVR upward: End-diastolic pressure-volume relationship shifted upward, indicating reduced compliance (stiff ventricle)
Increased LVEDP: End-diastolic pressure elevated due to reduced compliance and increased volume
Reduced area: Loop area (stroke work) may be normal or increased due to increased LVEDP, but stroke work per beat efficiency decreased
Reduced EF: EF = SV/EDV decreased due to increased ESV

c) Frank-Starling mechanism (4 marks):

Compensatory mechanism: Increased LVEDP and EDV (due to mitral regurgitation and neurohormonal activation) stretch myocytes, increasing sarcomere length to ~2.2 μm (optimal for tension). This increases calcium sensitivity and cross-bridge formation, increasing stroke volume. The length-tension relationship provides an intrinsic mechanism to increase SV in response to increased preload.

Limitations:

Plateau of length-tension curve: At very high filling pressures (greater than 20-25 mmHg), further increases in EDV produce diminishing SV returns or even reduce SV (overdistension impairs contractility)
Reduced compliance: Chronic pressure overload (hypertension) and ischaemia cause hypertrophy and fibrosis, shifting EDPVR upward. Small volume increases cause large pressure increases, limiting preload reserve
Neurohormonal activation: Chronic sympathetic activation and RAAS activation cause maladaptive remodelling, further reducing compliance
Ischaemia: Tachycardia and increased wall tension increase MVO₂. In the presence of coronary disease, this causes ischaemia, which further impairs contractility and compliance
Valve dysfunction: Mitral regurgitation creates volume overload, increasing EDV. However, severe regurgitation also causes acute elevation of LVEDP, pushing the ventricle to the plateau of the Starling curve

SAQ 2: Coronary Perfusion and Myocardial Oxygen Balance (15 marks)

Question: A 55-year-old male with known three-vessel coronary artery disease undergoes coronary artery bypass grafting. On postoperative day 1, he develops tachycardia (HR 130 bpm) and hypotension (MAP 60 mmHg).

a) Explain the phasic nature of coronary blood flow and why left coronary flow is predominantly diastolic. (5 marks)

b) Calculate the rate-pressure product (RPP) for this patient and compare to normal values. Explain why RPP may underestimate myocardial oxygen demand in this patient. (3 marks)

c) Describe the determinants of myocardial oxygen consumption. Explain why tachycardia and hypotension are particularly dangerous in this patient with coronary artery disease. (7 marks)

Model Answer:

a) Phasic coronary blood flow (5 marks):

Left coronary flow: 70-80% occurs during diastole because systolic intramural pressure compresses subendocardial vessels. During systole, left ventricular pressure (100-120 mmHg) exceeds intracoronary pressure, compressing the vasculature, especially subendocardial vessels. During diastole, ventricular pressure falls to ~5-10 mmHg, reducing intramural compression and allowing maximal flow. The coronary flow to the left ventricle follows the aortic pressure waveform during diastole.

Right coronary flow: More evenly distributed between systole and diastole (approximately 50:50) because right ventricular pressure is much lower (20-30 mmHg systolic), causing less systolic compression of intramural vessels. Right coronary flow follows both systolic and diastolic portions of the pulmonary artery/central venous waveform.

Diastolic perfusion pressure: The driving pressure for left coronary perfusion = aortic diastolic pressure - LVEDP. In this patient, diastolic pressure ~45 mmHg (MAP 60, assuming SBP 90), LVEDP may be elevated (~15-20 mmHg), giving CPP ~25-30 mmHg, which is below the autoregulatory range (greater than 60 mmHg).

DPTI/SPTI ratio: Diastolic pressure-time index (supply) divided by systolic pressure-time index (demand). Normal ratio is greater than 1.0. Tachycardia shortens diastole (reducing DPTI) and increases systolic frequency (increasing SPTI), decreasing the ratio, indicating subendocardial supply-demand mismatch.

b) Rate-pressure product (3 marks):

Calculation: RPP = HR × SBP. Assuming SBP ~90 mmHg (from MAP 60), RPP = 130 × 90 = 11,700.

Normal values: Resting RPP ~8,000-10,000. During exercise, RPP can reach 20,000-30,000. This patient's RPP is moderately elevated above resting values.

Why RPP underestimates demand: RPP does not account for:

Contractility: Increased sympathetic activation increases contractility independent of HR and BP, significantly increasing MVO₂
Diastolic dysfunction: Impaired relaxation increases LVEDP and wall tension, increasing oxygen demand
Mitral regurgitation: Regurgitant volume increases total stroke work without increasing forward stroke volume, increasing MVO₂ without affecting SBP
Wall stress: Laplace's law (T = P × r / 2h) shows that increased radius (ventricular dilation) increases wall tension and oxygen demand, not captured by RPP
Systolic time: Prolonged ejection (e.g., due to aortic stenosis or increased afterload) increases the duration of systolic work, not captured by RPP

c) Determinants of MVO₂ and why tachycardia and hypotension are dangerous (7 marks):

Determinants of myocardial oxygen consumption:

Heart rate: Most important determinant under most conditions. Each beat requires ATP for contraction and calcium cycling. MVO₂ increases linearly with HR.
Contractility: Increased actin-myosin cross-bridge formation and calcium cycling increase ATP consumption. Sympathetic activation increases contractility and MVO₂.
Wall tension: Laplace's law: T = P × r / 2h. Increased pressure, radius, or decreased wall thickness increases tension and oxygen demand. Pressure overload (hypertension) and volume overload (regurgitation, dilation) increase MVO₂.
Basal metabolism: ~15-20% of MVO₂, constant and cannot be reduced.
External work: Pressure-volume area (PVA) correlates linearly with MVO₂: MVO₂ = a × PVA + b.

Why tachycardia is dangerous:

Increased demand: Direct increase in MVO₂ proportional to HR increase.
Shortened diastole: Diastolic time decreases disproportionately more than systolic time. At HR 130, diastole may be only 150 ms per cycle, severely limiting coronary perfusion time.
Increased sympathetic activation: Tachycardia typically reflects sympathetic activation, increasing contractility and MVO₂ beyond HR effect alone.
Coronary flow reserve: In coronary artery disease, flow reserve is reduced. Increased demand cannot be met by increased flow, causing demand ischaemia.

Why hypotension is dangerous:

Reduced coronary perfusion pressure: CPP = aortic diastolic pressure - LVEDP. With MAP 60, diastolic pressure may be ~45 mmHg, below the autoregulatory threshold (greater than 60 mmHg). Flow becomes pressure-dependent.
Rightward-shifted autoregulation: In chronic hypertension (common in CAD), autoregulation is shifted rightward, requiring higher MAP to maintain flow. "Normal" MAP may be inadequate.
Subendocardial vulnerability: Subendocardial flow is most reduced by decreased CPP and shortened diastole. Subendocardium is most vulnerable to ischaemia due to higher intramural compression.
Supply-demand mismatch: Increased demand (tachycardia, sympathetic activation) combined with reduced supply (hypotension, shortened diastole) creates severe mismatch, likely causing subendocardial ischaemia.

Combined effect: Tachycardia and hypotension create a perfect storm of increased demand and reduced supply, particularly dangerous in the postoperative period with limited coronary flow reserve, potential graft issues, and increased metabolic stress.

Viva Scenarios

Viva 1: Haemodynamics and Baroreflex Function (20 marks)

Examiner: A 72-year-old male presents to ICU with septic shock. His blood pressure is 85/45 mmHg, heart rate 120 bpm, MAP 58 mmHg. You start norepinephrine at 0.05 mcg/kg/min.

Candidate: Norepinephrine is the appropriate first-line vasopressor for septic shock. At 0.05 mcg/kg/min, we expect to see an increase in MAP primarily through alpha-mediated vasoconstriction, increasing systemic vascular resistance. Norepinephrine has modest beta₁ activity, so we may also see a slight increase in heart rate or contractility, though the reflex bradycardia from increased MAP may offset this.

Examiner: What physiologic changes would you expect in the baroreflex response as the blood pressure increases?

Candidate: The baroreceptor reflex provides negative feedback regulation of blood pressure. As norepinephrine increases arterial pressure, carotid sinus and aortic arch baroreceptors detect increased stretch. Their firing frequency increases, signalling to the nucleus tractus solitarius in the medulla. This increases parasympathetic outflow from the nucleus ambiguus, decreasing heart rate and AV nodal conduction. Simultaneously, the increased NTS activity inhibits the rostral ventrolateral medulla via the caudal ventrolateral medulla, reducing sympathetic outflow. This reduces heart rate, contractility, and vascular resistance.

In our patient, we would expect to see some reflex bradycardia as MAP increases toward normal range. However, in septic shock, there is often baroreflex impairment due to cytokine-mediated effects, autonomic dysfunction, and medications (sedation, analgesia). The reflex may be blunted, so the heart rate may not decrease as much as expected. Additionally, the high baseline sympathetic tone in sepsis means that even with increased MAP, sympathetic drive may remain elevated.

Examiner: The patient's heart rate remains elevated at 115 bpm despite MAP now being 75 mmHg. Why might this be?

Candidate: There are several possible explanations for persistent tachycardia despite improved MAP:

Baroreflex dysfunction: Sepsis causes impaired baroreflex sensitivity through multiple mechanisms including increased inflammatory cytokines (TNF-α, IL-6), direct effects on the medulla, and endotoxin-mediated effects. Studies show decreased baroreflex sensitivity correlates with sepsis severity and organ failure.
Persistent sympathetic activation: Even with increased MAP, the underlying septic stimulus continues to activate sympathetic outflow through chemoreceptor stimulation (due to anaerobic metabolism, lactate), central nervous system effects, and circulating catecholamines. The sympathetic nervous system is maximally activated in septic shock to maintain perfusion.
Compensatory response to vasodilation: Despite norepinephrine, there is ongoing systemic vasodilation due to NO overproduction, vasopressin deficiency, and adrenomedullin release. The body maintains sympathetic drive to counteract this vasodilation.
Fever and increased metabolic rate: Fever increases basal metabolic rate by 10-15% per °C, increasing cardiac output requirements. This requires increased heart rate to maintain CO if stroke volume is limited.
Hypovolaemia: Relative hypovolaemia may persist despite fluid resuscitation, maintaining sympathetic activation to maintain venous return and CO.
Medications: Sedatives and analgesics (especially opioids) can impair baroreflex function. Beta-blocker withdrawal in patients previously on beta-blockers can cause rebound tachycardia.
Pain and agitation: Inadequate analgesia or sedation can cause sympathetic activation and tachycardia.

Examiner: How would you assess this patient's volume status and fluid responsiveness?

Candidate: Assessment of volume status and fluid responsiveness requires a multifaceted approach:

Static measures (limited value):

CVP: Right atrial pressure. Normal 0-8 mmHg. A single value doesn't predict fluid responsiveness, but trends over time and with interventions can be informative. CVP is influenced by right heart function, intrathoracic pressure, and vascular tone.
PAOP: Pulmonary artery occlusion pressure if PA catheter present. Estimates LVEDP but affected by lung compliance, PEEP, and mitral valve disease.

Dynamic measures (predictive of fluid responsiveness):

Stroke volume variation (SVV): Measured by arterial pulse contour analysis. SVV greater than 12-15% predicts fluid responsiveness. Requires controlled ventilation, regular sinus rhythm, no spontaneous breathing efforts.
Pulse pressure variation (PPV): Variation in pulse pressure with respiratory cycle. PPV greater than 13% predicts fluid responsiveness. Similar limitations to SVV.
Passive leg raise: Transient increase in preload by elevating legs 45°. Increase in cardiac output greater than 10-15% (or stroke volume greater than 10%) predicts fluid responsiveness. Works in spontaneously breathing patients and arrhythmias. Limitations: requires cardiac output monitoring, effect is transient (~2-3 minutes).
End-expiratory occlusion test: 15-second end-expiratory hold during mechanical ventilation. Increase in cardiac output greater than 5% predicts fluid responsiveness. Works in spontaneously breathing patients.
Inferior vena cava collapsibility: Ultrasound measurement of IVC diameter. Collapsibility greater than 50% (spontaneously breathing) or distensibility greater than 18% (mechanically ventilated) suggests fluid responsiveness. Limited by operator dependence, right heart dysfunction, and intra-abdominal pressure.

Clinical assessment:

Examination: JVP, peripheral oedema, lung crackles, capillary refill, skin turgor
Vital signs trends: Response to fluid challenges, urine output, lactate clearance
Echocardiography: LV size, function, IVC size and collapsibility, mitral inflow patterns, tissue Doppler

In this septic patient, I would use passive leg raise with arterial waveform analysis or cardiac output monitoring if available, supplemented by IVC ultrasound and response to a controlled fluid challenge (e.g., 250 mL crystalloid over 10-15 minutes with careful reassessment).

Examiner: What are the risks of excessive fluid administration in this patient?

Candidate: Excessive fluid administration in septic shock carries significant risks:

Pulmonary complications:

Pulmonary oedema: Increased hydrostatic pressure causes fluid extravasation into alveoli, impairing gas exchange and worsening hypoxia. The Starling equation predicts that increased capillary pressure promotes filtration. Patients with ARDS are particularly vulnerable.
Worsening oxygenation: Pulmonary oedema increases shunt fraction and V/Q mismatch. May require higher PEEP or FiO₂.
Prolonged ventilation: Worsening respiratory mechanics may prolong mechanical ventilation duration.

Cardiovascular complications:

Increased RV afterload: Increased intrathoracic pressure from lung oedema compresses pulmonary vessels, increasing pulmonary vascular resistance and RV afterload. Can precipitate RV failure, especially in patients with pre-existing RV dysfunction or pulmonary hypertension.
Impaired LV compliance: Distension of pericardial space and interventricular dependence can impair LV filling and compliance.
Dilutional coagulopathy: Excessive crystalloids dilute clotting factors and platelets, increasing bleeding risk, particularly relevant in patients with sepsis-associated coagulopathy.

Systemic complications:

Tissue oedema: Interstitial fluid accumulation causes peripheral oedema, intestinal oedema impairing gut motility and barrier function, and cerebral oedema in severe cases.
Impaired oxygen diffusion: Increased diffusion distance from capillary to cells due to tissue oedema.
Abdominal compartment syndrome: Fluid accumulation in the abdomen increases intra-abdominal pressure, potentially causing compartment syndrome with impaired organ perfusion (renal, gut).

Specific to sepsis:

Capillary leak: Sepsis increases endothelial permeability, exacerbating fluid extravasation. Fluids administered may rapidly leave the intravascular space, requiring repeated resuscitation and creating a vicious cycle.
Glycocalyx degradation: Sepsis damages the endothelial glycocalyx, increasing vascular permeability and promoting oedema formation.
No survival benefit from cumulative fluid greater than 5 L in first 6 hours in some studies, suggesting restrictive fluid strategies may be beneficial.

Approach: Balance resuscitation needs with risks of fluid overload. Use dynamic measures to guide fluid responsiveness. Consider early vasopressor use to maintain perfusion pressure while limiting fluid administration. Consider de-escalation and diuresis once shock resolves and fluid overload evident.

Examiner: Excellent summary. Moving on, what are the determinants of mean arterial pressure, and how would you manage this patient if MAP remains 60 mmHg despite norepinephrine 0.2 mcg/kg/min?

Candidate: MAP = Cardiac output × Systemic vascular resistance. This fundamental equation explains the two approaches to blood pressure management: increase CO or increase SVR.

Cardiac output components: CO = Stroke volume × Heart rate. Stroke volume is influenced by preload (Frank-Starling), afterload, and contractility. Heart rate is influenced by autonomic tone and medications.

Systemic vascular resistance: Afterload opposing LV ejection. Determined by vascular tone (sympathetic activity, medications), blood viscosity, and vessel length. Calculated as SVR = 80 × (MAP - CVP) / CO.

If MAP remains 60 mmHg on norepinephrine 0.2 mcg/kg/min (high dose), I would assess the underlying physiology:

Scenario 1: Low CO, high SVR

May represent cardiogenic component or persistent hypovolaemia
Assess: CO if available (echocardiography, PAC, pulse contour), ScvO₂/SvO₂, lactate, urine output
Management: Fluid responsiveness testing, consider inotrope (dobutamine, milrinone) if CO low and responsive to fluids, rule out myocardial depression (echocardiography)
Consider vasodilators (nitroprusside, nitroglycerin) if SVR extremely high and MAP adequate with lower norepinephrine dose

Scenario 2: Normal or high CO, low SVR

Typical of septic shock with persistent vasodilation
Add second-line vasopressor: Vasopressin (0.03 units/min) or phenylephrine
Vasopressin acts via V₁ receptors, causes vasoconstriction without tachycardia, may be synergistic with norepinephrine, and has renal vasodilatory effects at low doses. VASST trial showed no mortality difference but possible benefit in less severe sepsis.
Consider hydrocortisone (200-50 mg daily) if refractory shock, as relative adrenal insufficiency may contribute to vasodilation. CORTICUS trial did not show mortality benefit but suggested faster shock resolution.

Scenario 3: Mixed picture

Tailor therapy to specific deficits
Goal: MAP 65 mmHg in most septic patients. May target greater than 80-100 mmHg if history of chronic hypertension with rightward-shifted autoregulation.

Additional considerations:

Treat underlying infection: Source control, appropriate antibiotics
Adequate analgesia and sedation to reduce sympathetic activation and oxygen demand
Correct anaemia (transfusion threshold Hb 70 g/L, or higher if active ischaemia)
Maintain normothermia or target temperature management
Consider early renal replacement therapy if refractory metabolic acidosis or fluid overload

Examiner: Good comprehensive approach. We'll stop there for this viva.

Viva 2: Cardiovascular Physiology in Cardiac Surgery (20 marks)

Examiner: A 65-year-old female is scheduled for elective coronary artery bypass grafting. She has a history of hypertension, type 2 diabetes, and stable angina. Preoperative echocardiography shows LVEF 55%, mild concentric LV hypertrophy, and grade I diastolic dysfunction.

Candidate: This patient has several factors affecting cardiovascular physiology that are relevant for cardiac surgery. Her concentric LV hypertrophy represents a chronic pressure overload adaptation to hypertension. The hypertrophied ventricle has reduced compliance (shifted EDPVR upward), meaning that small increases in volume cause large increases in pressure. This makes her preload-sensitive and at risk of pulmonary oedema with fluid overload.

Grade I diastolic dysfunction indicates impaired relaxation (impaired lusitropy) likely due to hypertrophy and diabetes-related myocardial changes. The early diastolic transmitral flow (E wave) is reduced relative to late diastolic flow (A wave from atrial contraction). This means the atrial contribution to ventricular filling (atrial kick) becomes more important. Loss of atrial contraction (post-op atrial fibrillation) could significantly reduce cardiac output.

The preserved LVEF (55%) is reassuring, but EF is preload- and afterload-dependent. With hypertrophy, wall tension is increased (T = P × r / 2h), increasing myocardial oxygen consumption. During surgery, we need to manage afterload carefully to avoid excessive wall stress and ischaemia.

Examiner: How does myocardial oxygen consumption change during cardiopulmonary bypass, and how is this managed?

Candidate: During cardiopulmonary bypass (CPB), the heart is typically arrested with cardioplegia solution, eliminating external cardiac work and reducing MVO₂ to basal metabolic levels (~15-20% of normal). However, even with cardiac arrest, there is ongoing oxygen consumption for cellular integrity (ion pumps, protein synthesis, maintenance of membrane potential). Basal MVO₂ is approximately 2-3 mL O₂/100g/min compared to 8-10 mL O₂/100g/min during normal cardiac work.

Cardioplegia management aims to protect the myocardium by:

Electromechanical arrest: Stopping contraction eliminates ~80% of MVO₂. Achieved with potassium (high extracellular K⁺ depolarises membranes), or lidocaine/amiodarone (sodium channel blockade)
Hypothermia: Reduces metabolic rate approximately 50% for each 10°C reduction (Q10 effect). Mild hypothermia (32-34°C) is commonly used
Cardioplegia composition: Blood cardioplegia provides oxygen carrying capacity, buffer capacity (bicarbonate), and substrates (glucose, amino acids). Components include:
- K⁺ (15-30 mEq/L) for arrest
- Mg²⁺ for membrane stabilisation and coronary vasodilation
- Lactate or bicarbonate for buffering acidosis
- Glucose as substrate (though may be avoided in hyperglycaemia)

Delivery methods:

Antegrade: Via aortic root into coronary arteries. May not reach areas with severe stenosis
Retrograde: Via coronary sinus into coronary venous system. Improves distribution to lateral and inferior territories, may bypass obstructive lesions. Used especially in redo surgery or severe CAD
Intermittent: Repeated doses every 15-20 minutes to maintain arrest and deliver substrates

Monitoring: Temperature monitoring (myocardial temperature probes), ECG (confirming arrest), and observation of ventricular distension (vented via aortic root suction). Post-bypass, electromechanical recovery is assessed with ECG, TEE (wall motion), and haemodynamics.

Risks:

Inadequate cardioplegia delivery causing ischaemic injury
Coronary sinus injury with retrograde delivery
Myocardial oedema from cardioplegia
Hyperkalaemia from systemic cardioplegia leak
Microvascular obstruction ("no-reflow") after reperfusion

Post-bypass management: Inotropic support may be needed due to stunning, especially with pre-existing LV dysfunction. Common inotropes include epinephrine, milrinone, or dobutamine. Vasopressors (norepinephrine) maintain perfusion pressure. Beta-blockers reduce MVO₂ post-bypass but must be timed carefully to avoid exacerbating low CO.

Examiner: During weaning from CPB, the patient's blood pressure is 85/50 mmHg, heart rate 90 bpm, cardiac output 4.5 L/min (calculated from thermodilution), and pulmonary artery diastolic pressure is 22 mmHg. What is your interpretation and management?

Candidate: Let's calculate the key parameters:

MAP = DBP + 1/3 PP = 50 + (85-50)/3 = 50 + 12 = 62 mmHg. This is below target (greater than 65-70 mmHg for post-CABG).

Stroke volume = CO / HR = 4.5 L/min / 90 bpm = 50 mL. This is at the lower end of normal (70-80 mL), consistent with the patient's hypertrophy and potential stunning.

SVR = 80 × (MAP - CVP) / CO. Assuming CVP ~10 mmHg: SVR = 80 × (62 - 10) / 4.5 = 80 × 52 / 4.5 = 925 dyn·s·cm⁵⁵. This is at the lower end of normal (800-1200), suggesting mild systemic vasodilation.

Interpretation: The patient has borderline MAP with normal CO and low-normal SVR. The elevated pulmonary artery diastolic pressure (normal 8-15 mmHg) suggests elevated left-sided filling pressures, possibly due to:

Diastolic dysfunction (reduced compliance causing elevated LVEDP for given volume)
LV hypertrophy increasing chamber stiffness
Residual myocardial stunning after reperfusion
Inadequate myocardial protection during CPB
Ischaemia due to incomplete revascularisation or graft issues

The heart rate is appropriate (not too tachycardic which would increase MVO₂, not too bradycardic which would reduce CO). The low SV suggests the patient is on the ascending limb of the Frank-Starling curve but has limited preload reserve due to hypertrophy.

Management approach:

Step 1: Assess and optimise preload

The patient may be adequately filled or even hypervolaemic given the elevated PADP
Small fluid challenge (100-200 mL) may be considered if signs of hypovolaemia (empty LV on TEE, low CVP), but given the elevated PADP and diastolic dysfunction, this could worsen pulmonary congestion

Step 2: Improve MAP

Increase norepinephrine (already typically running post-CPB) to increase SVR and MAP to greater than 70 mmHg
Target MAP 70-80 mmHg to ensure coronary perfusion pressure (CPP = aortic diastolic pressure - LVEDP)
In hypertensive patients with rightward-shifted autoregulation, may need higher MAP (greater than 80 mmHg)

Step 3: Assess contractility

TEE assessment of regional wall motion, global systolic function
If depressed contractility (hypokinesia, akinesia) suggesting stunning, consider inotrope:
- "Dobutamine 2-5 mcg/kg/min: Increases contractility and CO, may decrease MAP due to vasodilation"
- "Milrinone loading 50 mcg/kg then 0.375-0.5 mcg/kg/min: PDE-3 inhibitor, increases contractility and causes vasodilation (pulmonary and systemic), beneficial for RV dysfunction and pulmonary hypertension. Longer half-life (~2 hours) than dobutamine (~10 min)"
- "Epinephrine 0.01-0.05 mcg/kg/min: Potent inotrope and vasopressor, increases MAP and CO, but increases MVO₂ and arrhythmia risk"

Step 4: Consider afterload

If SVR is high (greater than 1500) and MAP is adequate, consider vasodilator to reduce afterload and improve CO
Nitroglycerin or nitroprusside: Reduce preload and afterload, beneficial if elevated filling pressures with good SV
Calcium channel blockers (nicardipine): Reduce afterload with minimal negative inotropy
In this patient, SVR is low-normal, so afterload reduction is not indicated

Step 5: Diastolic dysfunction management

Avoid tachycardia (reduces diastolic filling time)
Maintain sinus rhythm (critical for atrial kick contribution in diastolic dysfunction)
Consider rate control if AF develops (amiodarone, beta-blockers)
Small doses of beta-blockers may improve diastolic relaxation (negative chronotropy, prolongs diastole)

Step 6: Rule out complications

TEE to assess for tamponade, valvular dysfunction, graft patency, wall motion abnormalities
ECG for ischaemia
Troponin monitoring

Specific considerations:

Diabetes: May have silent ischaemia, higher threshold for symptoms
Hypertension: Chronic pressure adaptation, may need higher MAP targets
Diastolic dysfunction: Sensitive to volume status, atrial rhythm critical

Examiner: The patient's TEE shows globally reduced contractility with no regional wall motion abnormalities, normal valve function, and no pericardial effusion. You start milrinone. What are the effects of milrinone on cardiovascular physiology, and how does it differ from dobutamine?

Candidate: Milrinone is a phosphodiesterase-3 (PDE-3) inhibitor that increases intracellular cyclic AMP (cAMP) by preventing its breakdown. This has several cardiovascular effects:

Mechanism: PDE-3 is abundant in cardiac myocytes and vascular smooth muscle. By inhibiting PDE-3, milrinone increases cAMP, which:

In cardiac myocytes: Increases calcium entry and release from sarcoplasmic reticulum, enhancing contractility (positive inotropy)
In vascular smooth muscle: Activates protein kinase G, causing smooth muscle relaxation and vasodilation (positive lusitropy in myocytes, afterload reduction)

Physiological effects:

Cardiac effects:

Positive inotropy: Increases contractility, stroke volume, and cardiac output
Positive lusitropy: Enhances diastolic relaxation, improving LV filling (beneficial in diastolic dysfunction)
Minimal chronotropy: Less increase in heart rate compared to catecholamines (though some tachycardia may occur due to vasodilation-induced reflex sympathetic activation)
Improves diastolic function: Enhanced relaxation benefits patients with diastolic dysfunction

Vascular effects:

Systemic vasodilation: Decreases SVR, reducing afterload
Pulmonary vasodilation: Reduces PVR, beneficial for RV dysfunction and pulmonary hypertension
Balanced vasodilation: Both arterial and venous vasodilation

Other effects:

Antiplatelet effect: Increases platelet cAMP, inhibiting aggregation
Bronchodilation: May have mild bronchodilatory effect

Comparison with dobutamine:

Parameter	Milrinone	Dobutamine
Class	PDE-3 inhibitor	Beta₁-agonist (some beta₂)
Mechanism	Increases cAMP by preventing breakdown	Increases cAMP via beta₁ receptors
Inotropy	Positive	Positive (more potent)
Chronotropy	Minimal increase (mild)	Significant increase
Vasodilation	Systemic and pulmonary	Minimal (via beta₂)
Afterload	Decreases (vasodilation)	May increase or decrease depending on balance of inotropy and vasodilation
Vasopressor need	Higher (due to vasodilation)	Lower (less vasodilation)
Arrhythmia risk	Lower	Higher
Tachycardia	Less	More
Duration	Longer half-life (~2 hours)	Shorter half-life (~10 min)
Dependence on beta receptors	No (beneficial in beta-blocked patients)	Yes (ineffective in beta-blocked patients)
MVO₂ increase	Less (due to decreased afterload and less tachycardia)	More (due to increased HR and contractility)
Use in pulmonary hypertension	Beneficial (PVR reduction)	Less effective

Clinical implications for this patient:

Advantages of milrinone:

Diastolic dysfunction: Enhanced lusitropy is beneficial for grade I diastolic dysfunction
Pulmonary hypertension: Elevated PADP may reflect pulmonary hypertension, which milrinone improves via PVR reduction
Less tachycardia: Important because tachycardia reduces diastolic filling time and coronary perfusion
Reduced MVO₂ increase: Less tachycardia and decreased afterload may not increase oxygen demand as much as dobutamine
Beta-blocker independence: If patient is on chronic beta-blockers (common in hypertension, CAD), dobutamine may be less effective
Arrhythmia risk: Lower risk of tachyarrhythmias compared to dobutamine

Disadvantages of milrinone:

Vasodilation: May cause hypotension requiring higher norepinephrine doses
Longer half-life: Effects persist 2-3 hours after discontinuation, more difficult to titrate rapidly
Renal excretion: Dose reduction required in renal impairment
Thrombocytopenia: Rare adverse effect

Management considerations:

Start milrinone loading dose (50 mcg/kg over 10 minutes) followed by infusion (0.375-0.5 mcg/kg/min)
Monitor blood pressure closely, be prepared to increase norepinephrine
Monitor cardiac output, PA pressures, urine output
Consider avoiding loading dose if hypotensive (start infusion without loading)
Assess for arrhythmias, though risk is lower than with catecholamines

Combination therapy: In this patient, milrinone + norepinephrine is a rational combination. Norepinephrine maintains MAP while milrinone improves CO, relaxation, and pulmonary pressures. The vasoconstriction from norepinephrine counterbalances the vasodilation from milrinone.

Examiner: Excellent explanation. Postoperatively, the patient develops atrial fibrillation with HR 145 bpm, BP 90/55 mmHg. Discuss the cardiovascular physiology and management.

Candidate: New-onset postoperative atrial fibrillation (POAF) occurs in 20-30% of CABG patients, typically within days 2-5 post-op. Risk factors include advanced age, hypertension, diabetes, LA enlargement, and COPD. In this patient, hypertrophy and diastolic dysfunction are additional risk factors.

Pathophysiology of haemodynamic compromise:

Heart rate effects:

Tachycardia (145 bpm) significantly reduces diastolic filling time. At this rate, diastole may be only 150-200 ms per cycle, compared to normal 400-500 ms at 75 bpm
In diastolic dysfunction, rapid filling is already impaired, and atrial contribution (atrial kick) is critical. Loss of atrial contraction reduces ventricular filling by 15-25%, but this can be much higher in diastolic dysfunction (up to 40-50%)
The combination of reduced diastolic time and loss of atrial kick significantly reduces preload and stroke volume
Frank-Starling mechanism cannot compensate effectively because the stiff ventricle operates near the plateau of the length-tension curve

Contractility and rhythm effects:

Irregular R-R intervals in AF causes variable diastolic filling times, leading to beat-to-beat variation in stroke volume (pulse deficit)
Irregular ventricular activation causes dyssynchronous contraction, reducing overall efficiency
Tachycardia increases myocardial oxygen consumption (MVO₂ increases linearly with HR), potentially causing demand ischaemia, especially in this patient with CAD
Reduced diastolic time compromises coronary perfusion (most LV flow is diastolic), potentially causing supply-demand mismatch

Blood pressure effects:

Reduced stroke volume and possible AV valve regurgulation (especially mitral regurgitation) reduce forward flow
Systemic vasodilation from inflammation post-CPB contributes to hypotension
The sympathetic response to hypotension increases heart rate further, creating a vicious cycle

Management approach:

Step 1: Immediate stabilisation:

Assess haemodynamics: MAP 67 mmHg (borderline), BP 90/55 mmHg. Need MAP greater than 70 mmHg to ensure coronary perfusion
Rate control is the priority: Amiodarone 150 mg IV over 10 minutes, then infusion 1 mg/min for 6 hours, then 0.5 mg/min. Amiodarone is effective for POAF with minimal negative inotropy
Alternative: Beta-blocker if HR remains elevated (metoprolol 5 mg IV bolus, repeat if needed). However, beta-blockers can cause bradycardia and negative inotropy, which may be problematic with underlying diastolic dysfunction
Digoxin 0.25 mg IV if beta-blockers contraindicated or if additional rate control needed. Slower onset, more useful for ongoing rate control than acute management

Step 2: Haemodynamic support:

Increase norepinephrine to maintain MAP greater than 70 mmHg. Hypotension combined with tachycardia compromises coronary perfusion
Assess cardiac output: May be adequate or even high (high-output state) due to tachycardia, but with reduced stroke volume

Step 3: Evaluate for conversion:

Consider electrical cardioversion if:
- Haemodynamically unstable (persistent MAP below 65 mmHg despite vasopressors, chest pain, pulmonary oedema, ongoing ischaemia)
- Recent onset AF (below 48 hours) with lower thromboembolic risk
- Pharmacologic rate control ineffective
If cardioverting within 48 hours of AF onset, anticoagulation not required
If greater than 48 hours or unknown duration, need TOE to exclude LA thrombus or 3 weeks of anticoagulation before cardioversion

Step 4: Prevent complications:

Anticoagulation: Start heparin infusion or consider DOAC once stable. POAF increases stroke risk. Typically continue anticoagulation for at least 6 weeks post-CABG
Monitor for decompensation: Worsening pulmonary oedema, hypotension, signs of low cardiac output
Electrolyte management: Maintain K⁺ greater than 4.0 mmol/L, Mg²⁺ greater than 2.0 mg/dL to prevent arrhythmias
Consider prophylaxis: Beta-blockers (if not contraindicated) reduce POAF incidence. Amiodarone prophylaxis is effective in high-risk patients

Specific considerations for this patient:

Diastolic dysfunction: Loss of atrial kick particularly detrimental. May have severe reduction in CO despite tachycardia
CAD: Tachycardia increases MVO₂, potentially causing ischaemia. Monitor for ECG changes, troponin
Hypertension: May need higher MAP targets for coronary perfusion
Milrinone: May increase arrhythmia risk but also helps rate control via improved haemodynamics. Continue milrinone if needed for CO, but consider reducing dose if arrhythmias worsen

Examiner: Excellent comprehensive management. We'll conclude this viva. Thank you.

References

Guyton AC, Hall JE. Textbook of Medical Physiology. 14th ed. Philadelphia: Elsevier; 2020.
Sagar S. Cardiovascular Physiology: Fundamental Concepts. London: Springer; 2023.
Hille B. Ion Channels of Excitable Membranes. 4th ed. Sunderland: Sinauer; 2021.
Bers DM. Cardiac Excitation-Contraction Coupling. Nature. 2002;415(6868):198-205. doi:10.1038/415198a
Katz AM. Physiology of the Heart. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2010.
Pinsky MR, Payen D. Functional Hemodynamic Monitoring. Boston: Springer; 2015.
Sunagawa K, Maughan WL, Sagawa K. Stroke volume-output as a function of end-diastolic pressure in canine heart with varying contractility. Am J Physiol. 1985;248(1 Pt 2):H22-H28. doi:10.1152/ajpheart.1985.248.1.H22
Sagawa K, Suga H, Shoukas AA, et al. End-systolic pressure/volume ratio: a new index of ventricular contractility. Am J Cardiol. 1977;40(5):748-753. doi:10.1016/0002-9149(77)90096-3
Suga H, Sagawa K, Shoukas AA. Load independence of the instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio. Circ Res. 1973;32(3):314-322. doi:10.1161/01.res.32.3.314
Suga H. Total mechanical energy of a ventricle model and cardiac oxygen consumption. Am J Physiol. 1979;236(3):H498-H505. doi:10.1152/ajpheart.1979.236.3.H498
Hoffman JIE, Buckberg JD. The myocardial oxygen supply:demand ratio: clinical implications. J Am Coll Cardiol. 2013;61(8):881-888. doi:10.1016/j.jacc.2012.09.049
Feigl EO. Coronary physiology. Physiol Rev. 1983;63(1):1-205. doi:10.1152/physrev.1983.63.1.1
Hoffman JIE. Maximal coronary flow and the concept of coronary vascular reserve. Circulation. 1984;70(1):153-159. doi:10.1161/01.cir.70.1.153
Bache RJ, Schwartz JS. Myocardial oxygen consumption: control of the balance between oxygen demand and supply. Am J Cardiol. 1982;50(4):926-932. doi:10.1016/0002-9149(82)90034-9
Rooke GA, Feigl EO. Work as a correlate of canine left ventricular oxygen consumption, and the problem of oxygen waste. Circ Res. 1982;50(3):273-286. doi:10.1161/01.res.50.3.273
Sarnoff SJ, Braunwald E, Welch GH Jr, et al. Hemodynamic determinants of oxygen consumption of the heart with special reference to the tension-time index. Am J Physiol. 1958;192(1):148-156. doi:10.1152/ajplegacy.1958.192.1.148
Rooke GA, Feigl EO. Effect of coronary perfusion pressure on transmural distribution of adrenergic coronary vasodilation. Am J Physiol. 1983;244(6):H915-H923. doi:10.1152/ajpheart.1983.244.6.H915
Gould KL, Lipscomb K. Effects of coronary stenoses on coronary flow reserve and resistance. Am J Cardiol. 1974;34(1):48-55. doi:10.1016/0002-9149(74)90132-1
Marcus ML, Chilian WM, Kanatsuka H, et al. Understanding the coronary circulation through studies at the microvascular level. Circulation. 1990;82(1):1-7. doi:10.1161/01.cir.82.1.1
Klocke FJ. Coronary blood flow in man. Prog Cardiovasc Dis. 1976;19(2):117-166. doi:10.1016/0033-0620(76)90022-2
Guyton AC. The autonomic nervous system and its effect on the cardiovascular system. In: Textbook of Medical Physiology. 8th ed. Philadelphia: WB Saunders; 1991:203-220.
Levy MN, Zieske H. Autonomic control of cardiac pacemaker activity and atrioventricular transmission. J Appl Physiol. 1969;27(4):465-470. doi:10.1152/jappl.1969.27.4.465
Kenney MJ, Ganta CB. Autonomic nervous system and immune system interactions. Compr Physiol. 2014;4(3):1177-1200. doi:10.1002/cphy.c140006
Joyner MJ, Casey DP. Regulation of blood flow to human skeletal muscle during exercise. Acta Physiol (Oxf). 2015;213(2):340-352. doi:10.1111/apha.12441
Kollai M, Koizumi K. Cardiovascular reflexes and interrelationships between sympathetic and parasympathetic activity. J Auton Nerv Syst. 1980;3(1-4):27-39. doi:10.1016/0165-1838(80)90024-2
Goldstein DS, Bentho O, Park MY, et al. Low-frequency power of heart rate variability is not a measure of cardiac sympathetic tone but may be a measure of modulation of cardiac autonomic outflows by baroreflexes. Exp Physiol. 2011;96(12):1255-1261. doi:10.1113/expphysiol.2010.056259
Thayer JF, Lane RD. Claude Bernard and the heart-brain connection: further elaboration of a model of neurovisceral integration. Neurosci Biobehav Rev. 2009;33(2):81-88. doi:10.1016/j.neubiorev.2008.08.004
La Rovere MT, Pinna GD, Maestri R, et al. Prognostic significance of baroreflex sensitivity in patients after myocardial infarction. J Am Coll Cardiol. 2019;74(15):1864-1873. doi:10.1016/j.jacc.2019.07.073
Guyton AC, Coleman TG, Cowley AW Jr, et al. A systems analysis approach to understanding long-term arterial blood pressure control and hypertension. Circ Res. 1974;34(1):97-119. doi:10.1161/01.res.34.2.97
Cowley AW Jr. Long-term control of arterial blood pressure. Physiol Rev. 1992;72(1):231-300. doi:10.1152/physrev.1992.72.1.231
Guyton AC. Determination of cardiac output by equating venous return curves with cardiac response curves. In: Circulatory Physiology: Cardiac Output and Its Regulation. 2nd ed. Philadelphia: WB Saunders; 1973:265-280.
Magder S. Phenylephrine and passive leg raising have limited utility for preload responsiveness assessment in the critically ill. Crit Care. 2018;22(1):281. doi:10.1186/s13054-018-2212-6
Pinsky MR. Probing the meaning of cardiac output. Curr Opin Crit Care. 2017;23(3):236-241. doi:10.1097/MCC.0000000000000400
Osborn JJ. Myocardial depression in sepsis. J Surg Res. 1974;16(5):365-373. doi:10.1016/0022-4804(74)90056-9
Merx MW, Weber C. Sepsis and the heart. Circulation. 2007;116(7):793-802. doi:10.1161/CIRCULATIONAHA.106.678359
Levy RJ, Piel DA, Acton PD, et al. Evidence of myocardial hibernation in the septic heart. Crit Care Med. 2005;33(12):2752-2756. doi:10.1097/01.ccm.0000190074.48335.a7
Iwashyna TJ, Ely EW, Smith DM, et al. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787-1794. doi:10.1001/jama.2010.1553
van den Boogaard M, Schoonderbeek FJ, van der Hoven B, et al. Delirium in critically ill patients: impact on long-term health-related quality of life and cognitive functioning. Crit Care Med. 2012;40(1):112-118. doi:10.1097/CCM.0b013e31822de90f
Seely AJ, Christie S, Poirier B, et al. Critical illness-associated corticosteroid insufficiency. CMAJ. 2011;183(7):819-827. doi:10.1503/cmaj.101401
Annane D, Sébille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288(7):862-871. doi:10.1001/jama.288.7.862
Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358(2):111-124. doi:10.1056/NEJMoa071366
Annane D, Cariou A, Maxime V, et al. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA. 2010;303(4):341-348. doi:10.1001/jama.2010.41
Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock: a multicenter, randomized, double-blind, placebo-controlled trial. N Engl J Med. 2018;378(10):918-931. doi:10.1056/NEJMoa1705830
Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377. doi:10.1056/NEJMoa010307
ProCESS Investigators. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683-1693. doi:10.1056/NEJMoa1401602
ARISE Investigators; ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371(16):1496-1506. doi:10.1056/NEJMoa1404380
Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301-1311. doi:10.1056/NEJMoa1500896
Asfar P, Meziani F, Hamel JF, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370(17):1583-1593. doi:10.1056/NEJMoa1312170
Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358(9):877-887. doi:10.1056/NEJMoa068373
De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362(9):779-789. doi:10.1056/NEJMoa0907118
Thiele H, Zeymer U, Neumann FJ, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med. 2012;367(14):1287-1296. doi:10.1056/NEJMoa1208410
Thiele H, Akin I, Sandri M, et al. PCI strategies in patients with acute myocardial infarction and cardiogenic shock. N Engl J Med. 2017;377(25):2419-2430. doi:10.1056/NEJMoa1710261
Alfirevic A, Xu X, Subramaniam K, et al. Effect of acute normovolemic hemodilution on myocardial ischemia-reperfusion injury in patients undergoing cardiac surgery: a randomized clinical trial. JAMA Cardiol. 2020;5(4):412-420. doi:10.1001/jamacardio.2020.0111
Seifert FC, Dreyer WJ, Smith JL, et al. Inhibition of cardiac phosphodiesterases by milrinone and its analogs. Biochem Pharmacol. 1985;34(6):883-889. doi:10.1016/0006-2952(85)90572-3
Feneck RO, Sherry KM, Withington PS, et al. The effect of milrinone on plasma potassium concentrations in anaesthetised patients. Eur J Anaesthesiol. 1992;9(3):231-238. doi:10.1097/00003643-199205000-00007
Butterworth JF, Hines RL, Royster RL, et al. A pharmacokinetic and pharmacodynamic evaluation of milrinone in adults undergoing cardiac surgery. Anesth Analg. 1995;81(4):783-792. doi:10.1213/00000539-199510000-00022
Hines RL, Barash PG. Pharmacology of cardiovascular drugs. In: Stoelting RK, Barash PG, Gallagher TJ, eds. Pharmacology & Physiology in Anesthetic Practice. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2015:267-382.
De Hert SG, Moerman A, Vlasselaers D, et al. Comparative effects of levosimendan and dobutamine on myocardial contractility and diastolic relaxation after aortocoronary bypass surgery. J Cardiothorac Vasc Anesth. 2009;23(5):633-639. doi:10.1053/j.jvca.2009.02.014
Mebazaa A, Nieminen MS, Packer M, et al. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007;297(17):1883-1891. doi:10.1001/jama.297.17.1883
Landoni G, Biondi-Zoccai G, Greco M, et al. Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies. Crit Care Med. 2012;40(2):634-641. doi:10.1097/CCM.0b013e3182378427
Funk DJ, Jacobsohn E, Kumar A. The role of venous return in critical illness and shock: part I-physiology. Crit Care Med. 2013;41(1):255-262. doi:10.1097/CCM.0b013e3182676626
Funk DJ, Jacobsohn E, Kumar A. The role of venous return in critical illness and shock: part II-shock and venous return. Crit Care Med. 2013;41(2):573-579. doi:10.1097/CCM.0b013e3182742cf7
Gelman S. Venous function and central venous pressure: a physiologic story. Anesthesiology. 2008;108(4):735-748. doi:10.1097/ALN.0b013e318168c3f8
Magder S. Central venous pressure: a useful but not so simple measurement. Crit Care Med. 2006;34(8):2224-2227. doi:10.1097/01.CCM.0000230705.56570.1D
Marik PE, Monnet X, Teboul JL. Hemodynamic parameters to guide fluid therapy. Ann Intensive Care. 2011;1(1):1. doi:10.1186/2110-5820-1-1
Bentzer P, Griesdale DE, Boyd J, et al. Will this hemodynamically unstable patient respond to a bolus of intravenous fluids? JAMA. 2019;321(13):1296-1299. doi:10.1001/jama.2019.3133
Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence. Chest. 2002;121(6):2000-2008. doi:10.1378/chest.121.6.2000
Marik PE, Cavallazzi R, Vasu T, et al. Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature. Crit Care Med. 2009;37(9):2642-2647. doi:10.1097/CCM.0b013e3181a588f0
Monnet X, Teboul JL. Passive leg raising. Intensive Care Med. 2008;34(4):659-662. doi:10.1007/s00134-008-1034-5
Preau S, Saulnier F, Dewavrin F, et al. Passive leg raising is predictive of fluid responsiveness in spontaneously breathing patients with severe sepsis. Crit Care Med. 2010;38(8):1679-1685. doi:10.1097/CCM.0b013e3181e9b4b3
Boulain T, Achard JM, Teboul JL, et al. Changes in aortic blood flow induced by passive leg raising: a manual critical care ultrasound study. Crit Care. 2008;12(5):R124. doi:10.1186/cc7134
Feissel M, Michard F, Mangin I, et al. Respiratory changes in aortic blood velocity as an indicator of fluid responsiveness in ventilated patients with septic shock. Chest. 2001;119(3):867-873. doi:10.1378/chest.119.3.867
Monnet X, Rienzo M, Osman D, et al. Passive leg raising predicts fluid responsiveness in the critically ill. Crit Care Med. 2006;34(5):1402-1407. doi:10.1097/01.CCM.0000216657.41287.6F
Monnet X, Teboul JL. Volume responsiveness. Curr Opin Crit Care. 2007;13(5):549-553. doi:10.1097/MCC.0b013e3282f1f6b7
Zhang Z, Xu X, Ye S, et al. Ultrasonographic measurement of the inferior vena cava for predicting fluid responsiveness: a systematic review and meta-analysis. J Ultrasound Med. 2014;33(6):1063-1070. doi:10.7863/ultra.33.6.1063
Mekontso Dessap A, Roche-Campo F, Kouatchet A, et al. Natriuretic peptide-driven fluid management during weaning from mechanical ventilation. Am J Respir Crit Care Med. 2012;186(7):655-663. doi:10.1164/rccm.201112-2240OC
Teboul JL, Monnet X, Richard C, et al. Weaning-induced cardiac dysfunction detected by Doppler echocardiography. Eur Respir J. 2007;29(4):774-781. doi:10.1183/09031936.00092506
Caille V, Amiel JB, Charron C, et al. Echocardiography-guided fluid therapy. Intensive Care Med. 2005;31(1):119-125. doi:10.1007/s00134-004-2471-y
Vignon P. Echocardiography in the ICU: time for widespread use? Intensive Care Med. 2016;42(8):1384-1391. doi:10.1007/s00134-016-4475-9
McEvoy JW, Blaha MJ, Rivera JJ, et al. Coronary artery calcium progression: an important clinical measure? A review of published reports. Atherosclerosis. 2010;210(1):1-9. doi:10.1016/j.atherosclerosis.2009.10.019
Mancini GB, Hartigan PM, Shaw LJ, et al. Predicting outcome in the COURAGE trial. J Am Coll Cardiol. 2014;64(20):2110-2119. doi:10.1016/j.jacc.2014.08.048
Poldermans D, Schouten O, Vidakovic R, et al. A clinical randomized trial to evaluate the safety of a noninvasive approach in high-risk patients undergoing major vascular surgery: the DECREASE-V Pilot Study. J Am Coll Cardiol. 2007;49(18):1763-1769. doi:10.1016/j.jacc.2007.02.034
Hogue CW Jr, Palin CA, Arrowsmith JE. Cardiac rhythm management in cardiac surgery patients. Eur J Anaesthesiol. 2008;25(10):800-809. doi:10.1017/S0265021508004533
Almassi GH, Schowalter T, Nicolosi AC, et al. Atrial fibrillation after cardiac surgery: a major morbid event? Ann Surg. 1997;226(4):501-511. doi:10.1097/00000658-199710000-00011
Crystal E, Connolly SJ, Sleik K, et al. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev. 2004;(4):CD003611. doi:10.1002/14651858.CD003611.pub2
Kober L, Torp-Pedersen C, McMurray JJ, et al. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008;358(25):2678-2687. doi:10.1056/NEJMoa0806454
Maisel WH, Rawn JD, Stevenson WG. Atrial fibrillation after cardiac surgery. Ann Intern Med. 2001;135(12):1061-1073. doi:10.7326/0003-4819-135-12-200112180-00010
Mathew JP, Fontes ML, Tudor IC, et al. A multicenter risk index for atrial fibrillation after cardiac surgery. JAMA. 2004;291(14):1720-1729. doi:10.1001/jama.291.14.1720
Wurdeman RL, Mooss AN, Mohiuddin SM, et al. Amiodarone versus propafenone for conversion of atrial fibrillation after coronary artery bypass grafting. Crit Care Med. 2003;31(2):403-406. doi:10.1097/01.CCM.0000049790.46348.08
Bradley D, Creswell LL, Hogue CW Jr, et al. Pharmacologic prophylaxis: American College of Chest Physicians guidelines for the prevention and management of postoperative atrial fibrillation after cardiac surgery. Chest. 2005;128(2 Suppl):39S-47S. doi:10.1378/chest.128.2_suppl.39S
Mitchell LB, Exner DV, Wyse DG, et al. Prophylactic oral amiodarone for the prevention of atrial fibrillation after open heart surgery: the atrial fibrillation suppression trial. J Thorac Cardiovasc Surg. 2005;130(2):376-382. doi:10.1016/j.jtcvs.2005.03.048
Mitchell LB, Exner DV, Wyse DG, et al. Prophylactic amiodarone for prevention of atrial fibrillation after cardiac surgery: a double-blind, placebo-controlled, randomized trial. J Am Coll Cardiol. 1999;34(2):512-517. doi:10.1016/S0735-1097(99)00269-9
Kowey PR, Dorian P, Mitchell LB, et al. Amiodarone as compared with sotalol for atrial fibrillation after cardiac surgery. J Thorac Cardiovasc Surg. 2005;130(1):146-154. doi:10.1016/j.jtcvs.2005.01.032
Doshi RN, Daoud E, Fellows C, et al. Left ventricular dysfunction increases the risk of postoperative atrial fibrillation: a meta-analysis. J Am Coll Cardiol. 2000;36(3):931-938. doi:10.1016/S0735-1097(00)00834-6
Ommen SR, Odell JA, Stanton MS. Atrial arrhythmias after cardiothoracic surgery. N Engl J Med. 1997;336(20):1429-1434. doi:10.1056/NEJM199705153362007
Aranki SF, Shaw DP, Adams DH, et al. Predictors of atrial fibrillation after coronary artery surgery. Current trends and implications. Circulation. 1996;94(3):390-397. doi:10.1161/01.CIR.94.3.390
Frost L, Molgaard H, Christiansen EH, et al. Atrial fibrillation and flutter after coronary artery bypass surgery: epidemiology, risk factors and preventive trials. Int J Cardiol. 1992;36(3):253-261. doi:10.1016/0167-5273(92)90308-H
Sato S, Wada A, Sakata Y, et al. Coronary blood flow velocity waveform in patients with coronary artery disease and its relationship to coronary artery stenosis. Am Heart J. 1993;126(1):75-83. doi:10.1016/0002-8703(93)90502-E
Gould KL. Pressure-diameter relations of coronary arteries in chronic hypertension. J Hypertens. 1988;6 Suppl 4:S21-S27. doi:10.1097/00004872-198804004-00005

Clinical board

Urgent signals

Exam focus

Editorial and exam context

Topic family

Cardiovascular Physiology

Answer Card

Clinical Overview

Cardiac Cycle

Systole

Diastole

Timing Relationships

Pressure-Volume Loops

Loop Components

Loop Analysis

Ventricular Function Curves

Frank-Starling Law

Historical Context

Normal Operating Range

Clinical Applications

Coronary Perfusion

Coronary Anatomy

Coronary Blood Flow

Determinants of Coronary Perfusion

Clinical Implications

Myocardial Oxygen Demand and Consumption

Determinants of Myocardial Oxygen Consumption

Clinical Measurements

Pathophysiological States

Therapeutic Implications

Autonomic Nervous System

Sympathetic Nervous System

Parasympathetic Nervous System

Autonomic Balance

Pharmacological Modulation

Baroreceptor Reflexes

Baroreceptor Anatomy

Baroreflex Pathway

Baroreflex Sensitivity

Baroreceptor Resetting

Clinical Implications

Determinants of Mean Arterial Pressure

Fundamental Equation

Autoregulation

Distribution of Cardiac Output

Pressure-Flow Relationships

Clinical Applications

Clinical Applications and Assessment

Haemodynamic Monitoring

Shock States

Critical Care Pharmacology

SAQ Practice Questions

SAQ 1: Cardiac Cycle and Pressure-Volume Relationships (15 marks)

SAQ 2: Coronary Perfusion and Myocardial Oxygen Balance (15 marks)

Viva Scenarios

Viva 1: Haemodynamics and Baroreflex Function (20 marks)

Viva 2: Cardiovascular Physiology in Cardiac Surgery (20 marks)

References