Difficulty: Intermediate | Prerequisites: Part 1 of these notes (cardiac electrophysiology and the cardiac cycle). You need to know the phases of the cardiac cycle and when valves open and close before tackling the volume and pressure relationships here.
This section covers how much blood the heart actually pumps per beat (stroke volume) and per minute (cardiac output), and the three factors that determine those numbers: preload, afterload, and contractility. The Frank-Starling mechanism is the centrepiece, explaining how the heart automatically adjusts its output to match venous return. The autonomic nervous system then layers on top of that intrinsic mechanism to fine-tune performance. These concepts underpin nearly all clinical scenarios involving exercise, haemorrhage, heart failure, and drug effects on the heart.
Cardiac output equals heart rate times stroke volume. Stroke volume equals end-diastolic volume minus end-systolic volume. Three things control stroke volume: preload (how stretched the ventricle is before it contracts), afterload (the pressure the ventricle must overcome to eject blood), and contractility (how forcefully the muscle fibres shorten, independent of stretch). The Frank-Starling mechanism means more filling leads to a stronger contraction automatically. Sympathetic stimulation increases both heart rate and contractility; parasympathetic stimulation (vagus nerve) primarily slows heart rate.
Cardiac output (CO)
The total volume of blood the heart pumps per minute. Calculated as heart rate multiplied by stroke volume (CO = HR × SV). A typical resting value is about 5 L/min. Think of it as the heart's overall "throughput."
Stroke volume (SV)
The volume of blood ejected by one ventricle per beat. Calculated as end-diastolic volume minus end-systolic volume (SV = EDV - ESV). Typical resting value is about 70 mL.
End-diastolic volume (EDV)
The maximum volume of blood in the ventricle at the end of filling (just before systole). In simple terms, it is how much blood is loaded into the chamber before it squeezes.
End-systolic volume (ESV)
The volume of blood remaining in the ventricle after contraction. The heart never empties completely. In simple terms, it is the leftover blood after each beat.
Preload
The degree of ventricular stretch at the end of diastole, directly related to EDV. More venous return means more filling, means more stretch, means greater preload. Think of it as how far you pull back a rubber band before releasing it.
Afterload
The pressure the ventricle must generate to open the semilunar valves and eject blood. For the left ventricle, afterload is largely determined by aortic pressure (and therefore by total peripheral resistance). Higher afterload makes it harder for the ventricle to empty, which tends to increase ESV and decrease SV.
Contractility (inotropic state)
The inherent strength of ventricular contraction, independent of preload or afterload. Increased contractility means the ventricle squeezes harder at the same stretch, ejecting more blood and leaving a lower ESV. Sympathetic stimulation and positive inotropic drugs increase contractility.
Frank-Starling mechanism (Starling's law of the heart)
The intrinsic property of the heart whereby increased ventricular filling (greater preload/EDV) stretches the cardiac muscle fibres to a more optimal length, producing a more forceful contraction and a larger stroke volume. In simple terms, the more the ventricle fills, the harder it contracts, all without any nerve input needed.
Ejection fraction (EF)
The percentage of EDV that is ejected per beat (EF = SV/EDV × 100). Normal is roughly 55-70%. A low ejection fraction is a hallmark of heart failure.
CO = HR × SV. This is the single most important equation for cardiac function.
If heart rate rises but stroke volume falls by the same proportion (for instance, because filling time is too short), cardiac output stays the same or even drops.
Normal resting CO is roughly 5 L/min. During heavy exercise it can increase to 20-25 L/min in a fit individual, primarily through increases in both HR and SV.
SV = EDV - ESV. Anything that increases EDV or decreases ESV will increase stroke volume.
Preload (EDV): increased venous return fills the ventricle more, raising EDV. The Frank-Starling mechanism then translates that extra stretch into a stronger contraction.
Afterload: increased afterload (higher aortic pressure, higher TPR) opposes ejection. The ventricle cannot empty as completely, so ESV rises and SV falls.
Contractility: increased contractility (e.g. from sympathetic stimulation or epinephrine) means the ventricle squeezes harder, reducing ESV and increasing SV.
This is an intrinsic property of cardiac muscle: stretch the sarcomeres to their optimal length and they produce more force.
It means the heart automatically matches output to input. If the right side receives more venous return, it pumps more to the lungs; the left side then receives more pulmonary venous return and pumps more to the body.
The mechanism does not require any neural or hormonal input. It works even in a denervated transplanted heart.
Sympathetic stimulation (norepinephrine, epinephrine):
Increases heart rate (positive chronotropic effect)
Increases contractility (positive inotropic effect)
Decreases ESV (the ventricle empties more completely)
Net result: increased cardiac output
Parasympathetic stimulation (vagus nerve, acetylcholine):
Decreases heart rate (negative chronotropic effect)
Has relatively little direct effect on ventricular contractility (the vagus innervates the atria more than the ventricles)
Net result: decreased cardiac output, primarily via reduced heart rate
If a patient has normal heart rate, increased EDV, and decreased ESV, stroke volume has increased (SV = EDV - ESV, and both changes push SV upward).
This pattern suggests enhanced preload and enhanced contractility working together.
Cardiac output: CO = HR × SV
Stroke volume: SV = EDV - ESV
Ejection fraction: EF = (SV / EDV) × 100%
Worked example 1: HR = 80 bpm, SV = 75 mL → CO = 80 × 75 = 6,000 mL/min = 6.0 L/min
Worked example 2: EDV = 140 mL, ESV = 60 mL, HR = 75 bpm → SV = 140 - 60 = 80 mL → CO = 75 × 80 = 6,000 mL/min = 6.0 L/min
Remember: CO = MAP / TPR (rearranged from MAP = CO × TPR). This links cardiac output to the blood pressure equation covered in Part 3.
The Frank-Starling mechanism is the reason a healthy heart can handle moment-to-moment changes in venous return without any conscious effort, for instance when you shift from lying down to standing or when one ventricle temporarily receives more blood than the other. In heart failure, the Starling curve flattens: extra filling no longer produces a proportionate increase in output, which is why fluid overload worsens symptoms rather than helping.
Students often think that increased heart rate always increases cardiac output. At very high heart rates (above roughly 160-180 bpm), filling time becomes so short that EDV drops, SV falls, and CO can actually decrease.
Students often confuse preload with afterload. Preload is about filling (how much blood is in the ventricle before contraction). Afterload is about resistance to ejection (how hard the ventricle has to push to get blood out).
Students sometimes think the Frank-Starling mechanism requires sympathetic input. It does not. It is intrinsic to the cardiac muscle itself and works in a denervated heart.
Students often assume that increased afterload increases stroke volume. The opposite is true: higher afterload opposes ejection, leaves more blood behind (higher ESV), and decreases SV.
⚠️ CO = HR × SV and SV = EDV - ESV are guaranteed exam territory. You will see calculation questions. Practise the arithmetic.
⚠️ Know what increases vs decreases SV: increased preload or contractility → increased SV; increased afterload → decreased SV.
⚠️ The Frank-Starling mechanism is a favourite conceptual question: "What happens when venous return increases?" Answer: EDV rises, the ventricle stretches more, contraction is stronger, SV increases.
⚠️ Sympathetic effects on the heart (increased HR and contractility) and parasympathetic effects (decreased HR via the vagus) are tested in both direct-recall and clinical-scenario formats.
⚠️ Expect clinical scenarios: "A patient has increased EDV and decreased ESV with normal HR. What has happened to stroke volume?" (It has increased.)
Fill in the blank: CO = ____ × ____. (HR × SV)
True or false: Increased afterload increases stroke volume. (False. It decreases SV by opposing ejection.)
Fill in the blank: The Frank-Starling mechanism states that increased ventricular ____ leads to increased force of contraction. (filling, or stretch, or preload/EDV)
True or false: Vagus nerve stimulation increases heart rate. (False. It decreases heart rate.)
A patient has EDV = 120 mL and ESV = 50 mL. What is the stroke volume? (70 mL)
Q: A patient has HR = 80 bpm and SV = 75 mL. What is the cardiac output?
A: CO = 80 × 75 = 6,000 mL/min = 6.0 L/min.
Q: EDV = 140 mL, ESV = 60 mL, HR = 75 bpm. What is the cardiac output?
A: SV = 140 - 60 = 80 mL. CO = 75 × 80 = 6,000 mL/min = 6.0 L/min.
Q: Which factor would most directly decrease stroke volume if all other variables remain constant?
A: Increased afterload. It opposes ventricular ejection, leaving more blood in the ventricle (higher ESV), so SV falls.
Q: According to Starling's law, increased venous return directly increases which variable?
A: Preload (EDV). More venous return fills the ventricle more, stretching the muscle fibres and producing a stronger contraction.
Q: Which condition would most likely increase end-systolic volume?
A: Increased afterload. The ventricle has to work against higher pressure and cannot empty as completely, leaving more blood behind.
Q: Which variable increases when sympathetic stimulation to the heart increases?
A: Contractility (and heart rate). The sympathetic nervous system has positive inotropic and positive chronotropic effects.
Q: Which factor would produce the greatest increase in stroke volume?
A: Increased contractility. It directly enhances the force of contraction, reducing ESV and increasing SV.
Q: Which statement best explains the Frank-Starling mechanism?
A: Greater ventricular filling (increased EDV/preload) stretches the cardiac muscle fibres to a more optimal length, producing a more forceful contraction and therefore a larger stroke volume.
Q: A researcher electrically stimulates the vagus nerve. What is the immediate response?
A: Decreased heart rate. The vagus nerve is parasympathetic and releases acetylcholine, which slows SA node depolarisation.
Q: A patient has normal HR, increased EDV, and decreased ESV. What is the most likely conclusion?
A: Stroke volume has increased, because SV = EDV - ESV, and both changes (higher EDV and lower ESV) increase SV.
Cardiac output feeds directly into the mean arterial pressure equation (MAP = CO × TPR), which is covered in Part 3 of these notes. Understanding how SV and HR change during exercise, haemorrhage, or standing up requires combining the pump mechanics here with the vascular and reflex concepts in Part 3. Preload and afterload also connect to fluid balance and capillary exchange: anything that changes blood volume (haemorrhage, dehydration, IV fluids) changes preload, and anything that changes TPR changes afterload.
Cardiac output, CO, stroke volume, SV, heart rate, HR, end-diastolic volume, EDV, end-systolic volume, ESV, preload, afterload, contractility, inotropy, Frank-Starling mechanism, Starling's law of the heart, ejection fraction, EF, sympathetic nervous system, parasympathetic nervous system, vagus nerve, acetylcholine, norepinephrine, epinephrine, chronotropic, inotropic, positive inotrope, venous return, cardiac function curve, APK2105, UF anatomy and physiology, Chapter 13, Chapter 14