18.02.04 · organismal-bio / cardiovascular

The cardiac cycle: systole and diastole, the Wiggers diagram, and cardiac output regulation

stub3 tiersLean: nonepending prereqs

Anchor (Master): Guyton, A. C. & Hall, J. E. — Textbook of Medical Physiology, 14th ed. (2021), Ch. 9-10

Intuition Beginner

Every heartbeat is a cycle with two main phases. Systole is when the heart muscle contracts and pumps blood out. Diastole is when the heart relaxes and fills with blood. These two phases alternate continuously: systole pushes blood forward, diastole refills the pump. At rest, the whole cycle takes about 0.8 seconds, with diastole lasting slightly longer than systole.

As the heart pumps, it makes two sounds — the familiar "lub-dub" heard through a stethoscope. The "lub" (first heart sound, S1) is produced when the atrioventricular valves (mitral and tricuspid) snap shut at the start of systole. The "dub" (second heart sound, S2) is produced when the semilunar valves (aortic and pulmonary) snap shut at the start of diastole. These sounds mark the boundaries between the phases.

Cardiac output is the total volume of blood the heart pumps each minute. It depends on two factors: how fast the heart beats (heart rate) and how much blood it ejects per beat (stroke volume). A resting adult typically has a heart rate of 72 beats per minute and a stroke volume of 70 mL, giving a cardiac output of about 5 litres per minute — roughly the entire blood volume recycled once every minute.

The heart adjusts its output to meet the body's needs. During exercise, both heart rate and stroke volume increase, raising cardiac output to 20-25 L/min in a trained athlete. The heart can do this because of a built-in property: when more blood returns to the heart (greater stretch of the muscle wall), the heart contracts more forcefully. This means the heart automatically pumps whatever volume it receives, without waiting for signals from the brain.

Visual Beginner

The Wiggers diagram is the master diagram of the cardiac cycle. It plots several quantities on the same time axis: left ventricular pressure, aortic pressure, left atrial pressure, ventricular volume, the electrocardiogram (ECG), and heart sounds. Reading the Wiggers diagram lets you see exactly how electrical, mechanical, and acoustic events line up during each heartbeat.

Starting from the left of the diagram: the QRS complex on the ECG triggers ventricular contraction. Ventricular pressure rises sharply while volume stays constant (all valves are closed — this is isovolumetric contraction). When ventricular pressure exceeds aortic pressure, the aortic valve opens and ejection begins. Pressure peaks, then falls. When ventricular pressure drops below aortic pressure, the aortic valve closes (producing S2), and isovolumetric relaxation follows. The mitral valve then opens and filling begins.

The volume trace on the Wiggers diagram shows ventricular volume dropping during ejection (from end-diastolic volume to end-systolic volume) and rising during filling. The difference between these two volumes is the stroke volume — the amount of blood pumped per beat.

Worked example Beginner

Calculate cardiac output and ejection fraction for a resting adult.

Given: heart rate = 75 beats/min, end-diastolic volume (EDV) = 120 mL, end-systolic volume (ESV) = 48 mL.

Step 1. Compute stroke volume:

SV = EDV - ESV = 120 - 48 = 72 mL/beat .

Step 2. Compute cardiac output:

CO = HR \times SV = 75 \times 72 = 5400 mL/min \approx 5.4 L/min .

Step 3. Compute ejection fraction (the fraction of blood ejected per beat):

EF = \frac{SV}{EDV} = \frac{72}{120} = 0.60 = 60%.

Both values are in the normal range (CO $\approx$ 5 L/min, EF 55-70%).

Check your understanding Beginner

Formal definition Intermediate+

Phases of the cardiac cycle

The cardiac cycle is a periodic process with period $T = 60/ HR$ seconds (HR in beats per minute). The left ventricular cycle comprises seven phases, each defined by valve states and the direction of pressure-volume change:

Atrial systole. The atrium contracts, delivering a final 20-30% of ventricular filling (the "atrial kick"). Ventricular pressure rises slightly. The P wave on the ECG precedes this phase.
Isovolumetric contraction. The mitral valve closes (S1). The ventricle contracts with all valves closed. Pressure rises rapidly from end-diastolic pressure ( $\sim$ 5-10 mmHg) toward aortic pressure ( $\sim$ 80 mmHg). Volume stays constant at EDV. Duration $\sim$ 50 ms.
Rapid ejection. When ventricular pressure exceeds aortic pressure, the aortic valve opens. Blood is ejected rapidly. Ventricular pressure continues to rise, reaching a peak of $\sim$ 120 mmHg. Aortic pressure follows ventricular pressure closely. The QRS complex precedes this phase.
Reduced ejection. Ejection rate slows. Ventricular pressure begins to fall below peak. The T wave (ventricular repolarisation) occurs during this phase, signalling the onset of relaxation. Duration of total ejection $\sim$ 300 ms.
Isovolumetric relaxation. Ventricular pressure drops below aortic pressure, the aortic valve closes (S2), and the ventricle relaxes with all valves closed again. Pressure falls rapidly while volume stays constant at ESV. Duration $\sim$ 60 ms.
Rapid filling. When ventricular pressure falls below atrial pressure, the mitral valve opens. Blood rushes passively from the atrium into the ventricle. A third heart sound (S3, sometimes heard in young adults or in volume-overloaded states) may occur during this phase.
Diastasis (slow filling). Filling rate decreases as ventricular and atrial pressures equalise. The ventricle is nearly full. This phase shortens at high heart rates and may disappear entirely during tachycardia.

Cardiac output, stroke volume, and ejection fraction

Cardiac output is:

CO = HR \times SV = HR \times (EDV - ESV) .

Ejection fraction is:

EF = \frac{SV}{EDV} = \frac{EDV - ESV}{EDV} .

Normal EF is 55-70%. An EF below 40% indicates systolic dysfunction.

The Wiggers diagram

The Wiggers diagram (Carl Wiggers, 1921) plots the following traces on a shared time axis:

Left ventricular pressure (LVP)
Aortic pressure (AP)
Left atrial pressure (LAP)
Left ventricular volume (LVV)
Electrocardiogram (ECG)
Phonocardiogram (heart sounds S1, S2)

The diagram reveals the temporal coordination of electrical, mechanical, and acoustic events. Key temporal correspondences include:

The QRS complex precedes the rise in ventricular pressure by $\sim$ 30 ms (the electromechanical delay).
Peak ventricular pressure coincides with peak aortic pressure during ejection.
The dicrotic notch (incisura) on the aortic pressure trace marks aortic valve closure at S2.
The a wave on the atrial pressure trace corresponds to atrial systole; the v wave corresponds to venous filling of the atrium during ventricular systole; the y descent marks rapid atrial emptying after mitral valve opening.

Determinants of cardiac output

Cardiac output is determined by heart rate and stroke volume. Stroke volume is in turn determined by three factors:

Preload is the degree of stretch of the ventricular wall at the end of diastole, approximated by EDV or end-diastolic pressure. Increased preload increases stroke volume via the Frank-Starling mechanism.

Afterload is the pressure the ventricle must overcome to eject blood. For the left ventricle, afterload is approximately aortic pressure (or more precisely, aortic input impedance). Increased afterload decreases stroke volume because the ventricle must generate more pressure before ejection can begin, leaving less time and energy for ejection.

Contractility (inotropy) is the intrinsic strength of contraction at a given preload and afterload. Increased contractility (sympathetic stimulation, positive inotropic drugs) shifts the end-systolic pressure-volume relationship leftward, reducing ESV and increasing stroke volume. Decreased contractility (heart failure, negative inotropic drugs) has the opposite effect.

The Frank-Starling mechanism

The Frank-Starling law states that the stroke volume of the ventricle increases in proportion to its end-diastolic volume (preload), within the physiological range. The mechanism arises because greater sarcomere stretch increases myofilament calcium sensitivity and optimises actin-myosin overlap, producing more forceful contraction.

The ventricular function curve plots stroke volume (or cardiac output) on the vertical axis against preload (EDV or end-diastolic pressure) on the horizontal axis. The curve is monotonically increasing but plateaus at high preload. Factors that shift the curve upward (increased contractility, sympathetic stimulation) allow greater SV at the same preload; factors that shift it downward (heart failure, acidosis) reduce SV at the same preload.

Key experiment Intermediate+

The Wiggers diagram as experimental synthesis (Wiggers, 1921).

Carl J. Wiggers used simultaneous optical recordings of ventricular pressure, aortic pressure, atrial pressure, and ventricular volume in anaesthetised dogs to produce the first comprehensive diagram of the cardiac cycle. By plotting these traces on a common time axis, he demonstrated that the phases of the cycle are defined by valve events (pressure crossovers), not by arbitrary time divisions.

Proposition (Pressure crossover determines valve state). A heart valve opens when the pressure on the upstream side exceeds the pressure on the downstream side, and closes when the pressure gradient reverses. No external control is required — valve motion is entirely passive, driven by the pressure differences generated by myocardial contraction and relaxation.

Derivation. Consider the aortic valve. Let $P_{V} (t)$ be left ventricular pressure and $P_{A o} (t)$ be aortic pressure. The net force on the valve leaflet in the opening direction is proportional to $P_{V} - P_{A o}$ .

During isovolumetric contraction, $P_{V}$ rises from $\sim$ 10 mmHg while $P_{A o}$ sits at diastolic pressure ( $\sim$ 80 mmHg). The valve remains closed because $P_{V} < P_{A o}$ .

When $P_{V}$ reaches and exceeds $P_{A o}$ (the pressure crossover), the net force reverses direction and the valve opens. Blood flows from ventricle to aorta.

During ejection, $P_{V}$ remains above $P_{A o}$ . As the ventricle begins to relax, $P_{V}$ falls. The moment $P_{V}$ drops below $P_{A o}$ , the pressure gradient reverses and the valve snaps shut, producing S2.

The same argument applies to the mitral valve, with $P_{L A}$ (left atrial pressure) and $P_{V}$ interchanged. The mitral valve opens when $P_{L A} > P_{V}$ (start of filling) and closes when $P_{V} > P_{L A}$ (start of systole). The pressure crossovers are deterministic consequences of the changing pressures, requiring no neural or muscular actuation of the valve leaflets. $□$

Bridge. The pressure-crossover principle explains why valvular heart disease distorts the Wiggers diagram. In aortic stenosis, the narrowed valve creates a pressure gradient even when open — ventricular pressure must rise far above aortic pressure to drive flow, producing a characteristically tall, wide PV loop. In mitral regurgitation, the incompetent valve allows backflow into the atrium during systole, so the "isovolumetric" phases are no longer truly isovolumetric.

Exercises Intermediate+

Exercise 3 (medium, short answer).

Explain why the diastasis phase of the cardiac cycle disappears during tachycardia (high heart rate), and what consequence this has for ventricular filling.

Hint

As heart rate increases, which phase shortens more — systole or diastole? What does this mean for the time available for filling?

Answer

Diastole shortens disproportionately more than systole as heart rate increases, because systole has a relatively fixed duration determined by the contraction-relaxation cycle of the myocyte. At high heart rates (e.g., 180 bpm), diastolic filling time may drop below 200 ms. The diastasis (slow filling) phase is sacrificed first, then even the rapid filling phase is compressed. Ventricular filling becomes increasingly dependent on the atrial kick, which is why loss of atrial contraction (atrial fibrillation) causes a disproportionate drop in cardiac output at high heart rates.

Exercise 4 (medium, numeric).

At rest, the cardiac cycle lasts 0.83 s (HR = 72 bpm). Systole occupies 0.30 s and diastole occupies 0.53 s. During exercise, HR rises to 150 bpm (cycle length = 0.40 s). If systole shortens modestly to 0.25 s, calculate diastolic filling time and the percentage reduction in filling time compared to rest.

Hint

Diastolic filling time = cycle length - systolic duration. Compare to the resting diastolic time.

Answer

Exercise diastolic time = $0.40 - 0.25 = 0.15$ s. Resting diastolic time = $0.53$ s. Percentage reduction = $(0.53 - 0.15) /0.53 \times 100 = 72%$ . Filling time drops by nearly three-quarters despite a "mere" doubling of heart rate. This underscores why diastolic filling time is a limiting factor at high heart rates and why the Frank-Starling mechanism (using increased venous return to drive more rapid early filling) is essential for maintaining stroke volume during exercise.

Exercise 5 (medium, short answer).

A patient's echocardiogram shows an ejection fraction of 35% with an enlarged EDV of 200 mL. Is this more likely systolic heart failure or diastolic heart failure? Explain using the determinants of stroke volume.

Hint

Systolic failure involves reduced contractility (low EF). Diastolic failure involves impaired filling (normal EF, high filling pressures). Which pattern matches these numbers?

Answer

This is systolic heart failure (heart failure with reduced ejection fraction, HFrEF). The EF of 35% is well below the 55% normal threshold, indicating impaired contractility — the ventricle cannot generate sufficient force to eject a normal fraction of its contents despite being dilated (EDV = 200 mL, well above the normal $\sim$ 120 mL). The ventricle has remodeled and dilated as a compensatory mechanism, using the Frank-Starling law to maintain stroke volume at the cost of operating at much higher wall stress (Laplace's law). SV = $0.35 \times 200 = 70$ mL, which is near normal — but only because of the massive preload reserve being consumed.

Exercise 6 (hard, symbolic).

Model the Frank-Starling relationship as $SV = k \cdot EDV^{α}$ with $k > 0$ and $0 < α < 1$ (a saturating curve). Derive the ejection fraction as a function of EDV and show that EF decreases as EDV increases. Interpret this result physiologically.

Hint

$EF = SV / EDV = k \cdot EDV^{α} / EDV = k \cdot EDV^{α - 1}$ . What happens as EDV grows when $α - 1 < 0$ ?

Answer

EF = \frac{SV}{EDV} = \frac{k \cdot EDV ^{α}}{EDV} = k \cdot EDV^{α - 1} .

Since $0 < α < 1$ , the exponent $α - 1$ is negative, meaning EF decreases as EDV increases. The derivative is:

\frac{d ( EF )}{d ( EDV )} = k (α - 1) \cdot EDV^{α - 2} < 0.

Physiologically, this captures the plateau of the Frank-Starling curve: as the ventricle dilates and EDV increases, stroke volume continues to rise but at a diminishing rate. The ejection fraction falls because each additional mL of preload yields a smaller increment in stroke volume. In dilated cardiomyopathy, the ventricle operates on the flat portion of this curve — further dilation adds preload without substantially increasing output, while wall stress rises proportionally to radius (Laplace's law), creating a deteriorating feedback loop.

Exercise 7 (hard, short answer).

On a Wiggers diagram, explain how the pressure traces would change in a patient with chronic aortic regurgitation. What happens to pulse pressure, left ventricular EDV, and the relationship between forward stroke volume and total stroke volume?

Hint

In aortic regurgitation, the aortic valve does not close fully. Blood leaks back from aorta into the ventricle during diastole.

Answer

In chronic aortic regurgitation, the incompetent aortic valve allows backflow during diastole. The Wiggers diagram shows: (i) aortic diastolic pressure falls rapidly during diastole (no dicrotic notch, or an attenuated one, because the valve never truly closes), producing a widened pulse pressure (high systolic, low diastolic); (ii) left ventricular volume increases throughout diastole as blood flows in both from the atrium (forward flow) and from the aorta (regurgitant flow), leading to a greatly increased EDV; (iii) the ventricle ejects a large total stroke volume (EDV minus ESV is large), but part of this volume regurgitates back during diastole, so the forward stroke volume (net output to the systemic circulation) is less than total SV. The ventricle compensates through eccentric hypertrophy (dilation with wall thickening that maintains normal wall stress by Laplace's law) and through the Frank-Starling mechanism (increased preload driving increased total SV). Eventually the volume overload exceeds the compensatory capacity, and the ventricle fails.

The pressure-volume loop, ESPVR, EDPVR, and the elastance model Master

The pressure-volume loop

The pressure-volume (PV) loop is a closed curve on the (V, P) plane that encodes the mechanical work performed by the ventricle in one cardiac cycle. Starting at the end-diastolic point (lower right), the loop proceeds counterclockwise through isovolumetric contraction (vertical line upward at constant EDV), ejection (top curve moving left as volume decreases), isovolumetric relaxation (vertical line downward at constant ESV), and filling (bottom curve moving right as volume increases).

The area enclosed by the PV loop equals the stroke work:

W_{stroke} = \oint P d V .

A normal resting left ventricle performs approximately 0.8-1.0 J of mechanical work per beat. At 72 bpm, this gives a mechanical power output of approximately 1.0-1.2 W.

End-systolic pressure-volume relationship (ESPVR)

The ESPVR is the locus of end-systolic points obtained by varying preload at constant contractility. Over the physiological range, the ESPVR is approximately linear:

P_{es} (V) = E_{es} \cdot (V - V_{0}),

where $E_{es}$ is the end-systolic elastance (mmHg/mL, a contractility index) and $V_{0}$ is the volume-axis intercept (the unstressed volume). Increased contractility (sympathetic stimulation, inotropic drugs) increases $E_{es}$ , rotating the ESPVR counterclockwise. Decreased contractility (heart failure, acidosis) decreases $E_{es}$ , rotating the ESPVR clockwise.

End-diastolic pressure-volume relationship (EDPVR)

The EDPVR describes the passive filling curve of the relaxed ventricle. It is approximately exponential:

P_{ed} (V) = α (e^{β (V - V_{0})} - 1),

reflecting the nonlinear stiffness of relaxed myocardium. At low volumes the ventricle is very compliant (small pressure change per unit volume). At high volumes, the exponential rise reflects the combined effects of myocardial stiffness, pericardial constraint, and ventricular interdependence. In diastolic heart failure (HFpEF), the EDPVR is shifted upward and leftward — the ventricle is stiffer, requiring higher filling pressures to achieve the same EDV.

The time-varying elastance model

Suga and Sagawa (1973) demonstrated that ventricular pressure can be described by a time-varying elastance function $E (t)$ :

P (t) = E (t) \cdot (V (t) - V_{0}),

where $E (t)$ rises from $E_{min}$ (end-diastolic stiffness, approximately equal to the slope of the EDPVR at the operating point) to $E_{max} = E_{es}$ at end-systole, then returns to $E_{min}$ . The key empirical finding is that $E (t)$ is approximately load-independent — its time course is determined by the contractile state of the myocardium and is not altered by changes in preload or afterload. This makes $E (t)$ a state function of the myocardium and elevates $E_{es}$ to a robust, load-independent index of contractility.

Pressure-volume area and myocardial oxygen consumption

The pressure-volume area (PVA) is the sum of stroke work (area inside the PV loop) and the triangular potential energy area between the ESPVR and the isovolumetric relaxation line. Suga (1979) demonstrated that PVA correlates linearly with myocardial oxygen consumption ( $VO_{2}$ ) per beat:

VO_{2} = a \cdot PVA + b,

where $a$ is the slope (the oxygen cost of mechanical work, independent of loading conditions) and $b$ is the intercept (basal metabolic oxygen consumption plus the oxygen cost of calcium cycling, which is contractility-dependent). Cardiac mechanical efficiency is:

η = \frac{W _{stroke}}{Δ H _{O_{2}} \cdot VO _{2}},

where $Δ H_{O_{2}} \approx 20 J/mL O_{2}$ is the enthalpy of oxygen consumption. Normal resting efficiency is 20-25%, comparable to skeletal muscle.

Contractility indices

The maximum rate of left ventricular pressure rise during isovolumetric contraction, dP/dt max, is a widely used contractility index:

(\frac{d P}{d t})_{m a x} .

Normal values are 1200-1500 mmHg/s for the left ventricle. dP/dt max increases with sympathetic stimulation and positive inotropic drugs; it decreases in systolic heart failure. Unlike $E_{es}$ , dP/dt max is somewhat afterload-dependent (it falls with increased afterload because isovolumetric contraction occupies a larger fraction of the pressure rise), but its preload-independence and the ease of measurement (via high-fidelity micromanometer catheters) make it clinically useful.

Valvular heart disease and the PV loop

Aortic stenosis. The narrowed valve creates a pressure gradient between the ventricle and aorta. Ventricular pressure rises far above aortic pressure during ejection. The PV loop shows a tall, narrow shape: the top of the loop is elevated (high peak systolic pressure) while stroke volume is reduced. The increased afterload causes concentric hypertrophy (wall thickening without chamber dilation) to normalise wall stress by Laplace's law.

Mitral regurgitation. The incompetent mitral valve allows backflow into the left atrium during systole. The PV loop loses its isovolumetric phases: volume decreases immediately as contraction begins (blood exits both the aorta and the atrium). Total stroke volume is increased, but forward stroke volume (net output to the aorta) is reduced. Chronic volume overload causes eccentric hypertrophy (chamber dilation with proportional wall thickening).

Systolic versus diastolic heart failure

In systolic heart failure (HFrEF), $E_{es}$ is reduced — the ESPVR rotates clockwise (less steep slope). The PV loop is shifted rightward (dilated ventricle, increased EDV) and shortened (reduced SV, low EF). The heart compensates by operating at higher preload (Frank-Starling mechanism) but at the cost of increased wall stress and progressive remodeling.

In diastolic heart failure (HFpEF), $E_{es}$ is approximately normal, but the EDPVR is shifted upward — the ventricle is stiffer and requires higher filling pressures to achieve adequate EDV. The PV loop appears narrow and tall (normal EF, small SV) but shifted upward on the pressure axis. The primary problem is impaired filling, not impaired contraction. The two failure modes produce nearly opposite PV-loop morphologies and require distinct therapeutic approaches.

Cardiac reserve and exercise

Cardiac reserve is the ratio of maximum cardiac output to resting cardiac output. In a healthy young adult, resting CO of 5 L/min can increase to 20-25 L/min during maximal exercise — a 4-5 fold reserve. This increase is achieved through:

Increased heart rate (from $\sim$ 72 to $\sim$ 180 bpm) — the dominant mechanism.
Increased stroke volume (from $\sim$ 70 to $\sim$ 120 mL) via increased venous return (preload), increased contractility (sympathetic activation, shifting the ESPVR upward), and decreased afterload (exercise vasodilation in skeletal muscle).
Increased oxygen extraction by tissues (expanding the arteriovenous oxygen difference from $\sim$ 5 to $\sim$ 15 mL O $_{2}$ /dL blood).

The Bainbridge reflex contributes to the heart rate response: increased venous return stretches stretch receptors in the right atrium and vena cava, sending afferent signals via the vagus nerve to the medulla, which responds by increasing sympathetic tone and decreasing vagal tone, raising heart rate. The Bainbridge reflex operates in the opposite direction to the baroreceptor reflex — increased venous return (which would raise blood pressure and activate the baroreflex to slow the heart) actually speeds the heart via the Bainbridge pathway. The net heart-rate response depends on which reflex dominates: at high filling pressures the Bainbridge reflex predominates, at low filling pressures the baroreflex predominates.

Connections Master

18.02.01 Cardiovascular physiology — the heart. The cardiac cycle is the temporal unfolding of the anatomy and pump geometry described in 18.02.01. Cardiac output, the Frank-Starling law, and the haemodynamic Ohm's law are all applied here to the time-resolved events of a single beat. The PV loop encodes the same stroke-work and efficiency information introduced in 18.02.01 but in a format that separates preload, afterload, and contractility effects.
18.02.02 Cardiac action potentials and pacemaker physiology. The electrical events on the Wiggers diagram (P wave, QRS complex, T wave) are the surface ECG reflections of the action-potential morphologies described in 18.02.02. Heart rate — a primary determinant of cardiac output — is set by the pacemaker mechanisms of the SA node and modulated by the autonomic inputs described there. The electromechanical delay between QRS and the onset of pressure rise reflects the time required for calcium-induced calcium release to activate the contractile machinery.
18.02.03 pending Hemodynamics. The afterload against which the ventricle ejects is the aortic input impedance described in 18.02.03. The Windkessel model determines the diastolic aortic pressure that the ventricle must overcome at the next beat. The Poiseuille framework explains why arteriolar vasodilation during exercise reduces afterload and facilitates increased stroke volume.
18.04.01 Skeletal muscle physiology and 18.04.02 Muscle contraction. The Frank-Starling mechanism is the cardiac-specific expression of the length-tension relationship introduced for skeletal muscle in 18.04.01 and the actin-myosin cross-bridge cycle of 18.04.02. The cardiac variant differs because cardiac myocytes operate on the ascending limb of the length-tension curve and exhibit length-dependent calcium sensitivity not present in skeletal muscle.
18.03.01 Respiratory physiology. Cardiac output determines pulmonary blood flow and hence the ventilation-perfusion matching treated in 18.03.01. During exercise, increased cardiac output increases pulmonary capillary recruitment and can raise pulmonary capillary pressure, potentially causing exercise-induced pulmonary oedema in pathological states.
18.08.01 Renal physiology. Cardiac output determines renal perfusion pressure and glomerular filtration rate. The RAAS axis described in 18.08.01 feeds back to regulate blood volume and hence cardiac preload. The Guyton pressure-natriuresis framework treats cardiac output as a variable in the long-term blood pressure equilibrium.

Historical notes Master

Carl J. Wiggers (1883-1963), a German-American physiologist at Western Reserve University in Cleveland, produced the definitive diagram of the cardiac cycle in his 1921 paper "Studies on the consecutive phases of the cardiac cycle" (American Journal of Physiology, 56, 415-438). Using optical manometers and tambour recording systems, Wiggers simultaneously measured ventricular pressure, aortic pressure, atrial pressure, and ventricular volume in anaesthetised dogs, plotting them on a common time axis. The diagram revealed that the phases of the cardiac cycle are bounded by valve events (pressure crossovers), not by arbitrary time intervals, and that electrical, mechanical, and acoustic events are tightly coupled. The Wiggers diagram remains the standard pedagogical tool for teaching the cardiac cycle, essentially unchanged in form from his original publication.

Otto Frank (1865-1944), working in Munich, established the length-tension relationship in cardiac muscle in 1895 (Zur Dynamik des Herzmuskels, Z. Biol. 32, 370-437). Using isolated frog ventricles, Frank demonstrated that the force of contraction increases with the initial stretch of the muscle — the observation that would later bear his name alongside Starling's. Frank's work was quantitative and rigorous: he constructed isometric and isotonic curves for cardiac muscle and recognised that the heart operates on the ascending limb of the length-tension relationship, unlike skeletal muscle which operates near the plateau.

Ernest Henry Starling (1866-1927), working at University College London, extended Frank's observation to the intact mammalian heart in a series of experiments with his collaborator William Bayliss and later with Ivan de Burgh Daly. In his 1918 Linacre Lecture ("The Law of the Heart"), Starling articulated the principle that the heart's output is governed by the volume of blood returning to it — what we now call the Frank-Starling law. Starling's insight was to recognise that this is an intrinsic property of cardiac muscle, not dependent on neural or hormonal regulation. The Frank-Starling mechanism ensures that the left and right ventricles automatically match their outputs: if one side temporarily pumps more than the other, the resulting redistribution of blood volume changes preload in a direction that restores balance.

Hiroyuki Suga and Kiichi Sagawa, working at Case Western Reserve University in the 1970s, developed the time-varying elastance model of the ventricle and the pressure-volume area framework. Suga's 1979 demonstration that PVA correlates linearly with myocardial oxygen consumption (Circulation Research, 44, 730-740) provided the first quantitative link between mechanical work and metabolic cost in the heart. Their work transformed cardiac physiology from a descriptive discipline to a quantitative one, introducing load-independent indices of contractility ( $E_{es}$ ) and efficiency that are now standard in both research and clinical cardiology.

The Bainbridge reflex was described by Francis Arthur Bainbridge in 1915 (Journal of Physiology, 50, 65-84). He observed that infusion of saline or blood into the venous system of anaesthetised dogs produced an increase in heart rate, mediated by stretch receptors in the right atrium and great veins. The reflex complements the baroreceptor reflex: whereas the baroreflex responds to arterial pressure, the Bainbridge reflex responds to venous return, ensuring that heart rate rises when filling increases even when arterial pressure is also rising (as during exercise).

Bibliography Master

Wiggers, C. J. (1921). Studies on the consecutive phases of the cardiac cycle. American Journal of Physiology, 56, 415-438.
Frank, O. (1895). Zur Dynamik des Herzmuskels. Zeitschrift fur Biologie, 32, 370-437.
Starling, E. H. (1918). The Linacre Lecture on the Law of the Heart. Longmans, Green and Co., London.
Suga, H. and Sagawa, K. (1974). Instantaneous pressure-volume relationships and their ratio in the excised, supported canine left ventricle. Circulation Research, 35, 117-126.
Suga, H. (1979). Total mechanical energy of a ventricle model and cardiac oxygen consumption. Circulation Research, 44, 730-740.
Bainbridge, F. A. (1915). The influence of venous filling upon the rate of the heart. Journal of Physiology, 50, 65-84.
Guyton, A. C. and Hall, J. E. (2021). Textbook of Medical Physiology (14th ed.). Elsevier.
Sherwood, L. (2016). Human Physiology (9th ed.). Cengage.
Silverthorn, D. U. (2019). Human Physiology: An Integrated Approach (8th ed.). Pearson.
Katz, A. M. (2022). Physiology of the Heart (6th ed.). Lippincott Williams and Wilkins.
Boron, W. F. and Boulpaep, E. L. (2017). Medical Physiology (3rd ed.). Elsevier.
Sagawa, K., Maughan, L., Suga, H., and Sunagawa, K. (1988). Cardiac Contraction and the Pressure-Volume Relationship. Oxford University Press.

Prerequisites

18.02.01 pending
18.02.02 pending

Tier anchors

beginner: Sherwood, Human Physiology, 9th ed. (2016), Ch. 9
intermediate: Silverthorn, Human Physiology: An Integrated Approach, 8th ed. (2019), Ch. 14
master: Guyton, A. C. & Hall, J. E. — Textbook of Medical Physiology, 14th ed. (2021), Ch. 9-10

References

Sherwood, L. — Human Physiology, 9th ed. (Cengage, 2016) · Ch. 9 Cardiac Output and Blood Pressure
Silverthorn, D. U. — Human Physiology: An Integrated Approach, 8th ed. (Pearson, 2019) · Ch. 14 The Cardiovascular System — Cardiac cycle
Guyton, A. C. & Hall, J. E. — Textbook of Medical Physiology, 14th ed. (Elsevier, 2021) · Ch. 9-10 Cardiac output, cardiac cycle
Wiggers, C. J. — Studies on the consecutive phases of the cardiac cycle · Am. J. Physiol. 56 (1921) 415-438

Estimated time

beginner: 15m
intermediate: 30m
master: 45m