Difficulty: Intermediate | Prerequisites: Cardiac cycle basics (Part 1 of these notes), understanding of autonomic nervous system divisions.
Once you know how the heart cycles through its electrical and mechanical phases, the next question is: how much blood does it actually pump? This section covers the key output variables (cardiac output, stroke volume, ejection fraction), the factors that determine them (preload, afterload, contractility), and the intrinsic and extrinsic mechanisms that regulate pump performance. The Frank-Starling mechanism is the single most important concept here, and questions about it appear in many forms. This material links forward to blood pressure regulation: cardiac output is half of the equation that determines mean arterial pressure.
Cardiac output equals heart rate times stroke volume. Stroke volume depends on preload (how much the ventricle fills), afterload (the pressure the ventricle must overcome to eject), and contractility (the intrinsic strength of contraction). The Frank-Starling mechanism says that greater filling produces a greater force of contraction. Sympathetic stimulation increases heart rate and contractility; parasympathetic stimulation (and its blockade by atropine) mainly affects heart rate. Beta-1 agonists mimic sympathetic effects; beta-1 blockers oppose them.
Cardiac output (CO)
The volume of blood pumped by one ventricle per minute. In simple terms, it is the total flow rate leaving the heart. A normal resting value is roughly 5 L/min.
Stroke volume (SV)
The volume of blood ejected by one ventricle per beat. Calculated as EDV minus ESV. Think of it as: how much blood leaves the ventricle each time it squeezes.
Heart rate (HR)
The number of ventricular contractions per minute.
End-diastolic volume (EDV)
The volume of blood in a ventricle at the end of filling (end of diastole), just before contraction begins. This is the measure of preload.
End-systolic volume (ESV)
The volume of blood remaining in a ventricle after contraction (end of systole). It reflects how completely the ventricle emptied.
Ejection fraction (EF)
The percentage of end-diastolic volume that is ejected per beat. Calculated as (SV / EDV) x 100%. A normal resting EF is roughly 55-70%. Think of it as the efficiency rating of the ventricle: what fraction of its contents does it actually pump out?
Preload
The degree of stretch on the ventricular wall at the end of diastole, determined by end-diastolic volume. Greater venous return increases preload.
Afterload
The pressure the ventricle must generate to open the semilunar valves and eject blood. In practical terms, it is closely related to arterial pressure and total peripheral resistance.
Contractility (inotropy)
The intrinsic ability of cardiac muscle to generate force, independent of preload and afterload. Increased contractility means a stronger squeeze at any given stretch. In simple terms, contractility is the "oomph" of the heartbeat, adjustable by the nervous system and drugs but not by how much blood is in the chamber.
Frank-Starling mechanism (Starling's law of the heart)
The principle that greater ventricular filling (greater preload) stretches cardiac muscle fibres, which then contract with greater force and eject a greater stroke volume. Think of it as: the more you fill it, the harder it squeezes. This is an intrinsic property of the heart, requiring no neural input.
Sympathetic stimulation (cardiac)
Noradrenaline acting on beta-1 adrenergic receptors on the heart increases heart rate (chronotropy), contractility (inotropy), and conduction velocity through the AV node (dromotropy). It also increases Ca2+ entry into cardiac cells.
Parasympathetic stimulation (cardiac)
Acetylcholine acting on muscarinic receptors on the SA and AV nodes slows heart rate and slows AV conduction. It has relatively little direct effect on ventricular contractility.
Beta-1 (β₁) agonist
A drug that activates beta-1 receptors, mimicking sympathetic stimulation to the heart. Expected effects: increased heart rate, increased contractility, increased Ca2+ entry.
Beta-1 (β₁) blocker
A drug that blocks beta-1 receptors, reducing the effects of sympathetic stimulation. Expected effects: decreased heart rate, decreased contractility, decreased AV conduction velocity.
Atropine
A muscarinic receptor antagonist that blocks parasympathetic (vagal) input to the heart. Because vagal tone normally restrains heart rate, blocking it increases heart rate.
Myocardial oxygen demand
The amount of oxygen the heart muscle requires, determined primarily by heart rate, contractility, and wall stress (which increases with afterload). Higher demand without matched supply leads to ischaemia.
CO = HR x SV (this is the correct and most fundamental equation)
SV = EDV - ESV
EF = (SV / EDV) x 100%
Example calculation (CO): HR = 75 bpm, SV = 80 mL/beat. CO = 75 x 80 = 6,000 mL/min = 6.0 L/min.
Example calculation (SV): EDV = 150 mL, ESV = 60 mL. SV = 150 - 60 = 90 mL.
Example calculation (EF): EDV = 160 mL, ESV = 80 mL. SV = 80 mL. EF = (80/160) x 100% = 50%.
Preload (EDV): More filling stretches the muscle fibres and, via the Frank-Starling mechanism, increases stroke volume. Preload is increased most directly by increased venous return.
Afterload: The pressure the ventricle must overcome. Higher afterload (e.g. chronic hypertension) makes it harder to eject blood, tends to increase ESV, and therefore decreases stroke volume. It also increases ventricular work and myocardial oxygen demand.
Contractility: Independent of stretch. Increased contractility decreases ESV (the ventricle empties more completely), increasing stroke volume and ejection fraction. Decreased contractility does the opposite.
Greater venous return fills the ventricle more (higher EDV, higher preload).
Greater stretch of sarcomeres optimises actin-myosin overlap and increases calcium sensitivity.
The ventricle contracts more forcefully and ejects a larger stroke volume.
This is an intrinsic mechanism: it does not require sympathetic nerves, hormones, or drugs.
The best one-line summary: greater ventricular filling produces greater force of contraction.
If EDV rises while heart rate and contractility stay the same, the Frank-Starling mechanism increases stroke volume. ESV may stay roughly the same or rise slightly, but the net effect is a larger SV because the ventricle was stretched further.
If EDV stays the same but ESV falls, the ventricle is emptying more completely. SV increases. The best explanation is increased contractility (the heart is squeezing harder at the same filling level).
Sympathetic activation (noradrenaline on β₁ receptors):
Increases heart rate (positive chronotropy)
Increases contractility (positive inotropy)
Increases AV conduction velocity (positive dromotropy)
Increases Ca2+ entry into cardiac cells
Net effect: higher CO, lower ESV, higher EF
Parasympathetic activation (acetylcholine on muscarinic receptors):
Decreases heart rate (negative chronotropy)
Slows AV conduction
Minimal direct effect on contractility
Net effect: lower HR, lower CO if SV does not compensate
β₁ agonist: mimics sympathetic stimulation. Expect increased contractility and increased heart rate.
β₁ blocker: opposes sympathetic stimulation. Expect decreased contractility, decreased heart rate, decreased AV conduction velocity.
Atropine: blocks parasympathetic input. Because the vagus normally slows the heart, blocking it removes that brake, and heart rate increases.
During moderate exercise, heart rate increases first (sympathetic activation and parasympathetic withdrawal).
Stroke volume also increases (due to increased venous return via the skeletal muscle pump, plus increased contractility from sympathetic drive).
During strenuous exercise, cardiac output rises substantially, while total peripheral resistance decreases (active vasodilation in skeletal muscle). The expected combination: increased CO, decreased TPR.
The left ventricle, because it must generate enough pressure to push blood through the entire systemic circulation. Typical peak systolic pressure in the left ventricle is around 120 mmHg, compared to roughly 25 mmHg in the right ventricle.
The left atrium. Pulmonary veins carry oxygenated blood from the lungs to the left atrium, which then passes it to the left ventricle for systemic ejection.
Increased afterload is a major driver of increased myocardial oxygen demand, because the ventricle must generate more wall stress to eject against higher pressure.
Increased heart rate also raises demand (more contractions per minute).
Decreased heart rate and reduced contractility lower demand.
Variable | Formula | Normal resting value |
|---|---|---|
Cardiac output | CO = HR x SV | ~5 L/min |
Stroke volume | SV = EDV - ESV | ~70 mL |
Ejection fraction | EF = (SV / EDV) x 100% | ~55-70% |
Note: MAP = HR x EDV is not a correct equation. Nor is SV = CO x HR or EF = HR / SV.
Ejection fraction is one of the most commonly measured clinical parameters in cardiology. An EF below roughly 40% indicates heart failure with reduced ejection fraction (HFrEF). Beta-blockers, despite seeming counterintuitive (they reduce contractility), are a cornerstone of heart failure treatment because they lower myocardial oxygen demand and allow the heart to remodel over time. Atropine is used clinically to treat symptomatic bradycardia by removing vagal braking.
Students often confuse preload with afterload. Preload is about filling (EDV, venous return). Afterload is about the resistance the ventricle ejects against (arterial pressure, TPR). They affect stroke volume in opposite directions.
A common error is thinking the Frank-Starling mechanism involves sympathetic nerves. It does not. It is an intrinsic property of cardiac muscle fibres responding to stretch.
Students sometimes think increased afterload increases cardiac output. It does the opposite in isolation: more afterload means more residual blood left behind (higher ESV), lower SV, and potentially lower CO unless compensated by other mechanisms.
Atropine is frequently mistaken for a sympathetic drug. It is a parasympathetic blocker. The heart rate rises because vagal tone is removed, not because sympathetic drive is added.
⚠️ Know CO = HR x SV cold. Be able to calculate CO, SV, and EF from given values.
⚠️ Understand the three determinants of stroke volume (preload, afterload, contractility) and how each affects SV.
⚠️ The Frank-Starling mechanism: "greater ventricular filling produces greater force of contraction." Expect it in multiple-choice phrasing.
⚠️ Know the cardiac effects of sympathetic vs parasympathetic stimulation, and the drug effects of β₁ agonists, β₁ blockers, and atropine.
⚠️ Be able to reason through clinical scenarios: "EDV increases, contractility unchanged, what happens to SV?" or "ESV decreases, EDV unchanged, what is the explanation?"
⚠️ The left ventricle generates the highest pressure during systole. The left atrium receives oxygenated blood from the lungs.
⚠️ Increased afterload increases myocardial oxygen demand.
Fill in the blank: CO = ___ x ___. ___
True or false: Ejection fraction is calculated as ESV / EDV x 100%. ___
Fill in the blank: The Frank-Starling mechanism states that greater ventricular ___ produces greater force of ___. ___
True or false: Atropine increases heart rate by stimulating beta-1 receptors. ___
Fill in the blank: The factor that MOST increases ejection fraction is increased ___. ___
Answers: 1. HR x SV. 2. False (SV / EDV x 100%). 3. filling, contraction. 4. False (it blocks muscarinic receptors, removing parasympathetic braking). 5. contractility.
Q: A patient has an EDV of 150 mL and an ESV of 60 mL. What is the stroke volume?
A: 90 mL (150 - 60 = 90).
Q: A patient has HR = 75 bpm and SV = 80 mL/beat. What is the cardiac output?
A: 6.0 L/min (75 x 80 = 6,000 mL/min).
Q: A patient has EDV = 160 mL and ESV = 80 mL. What is the ejection fraction?
A: 50% (SV = 80, EF = 80/160 x 100% = 50%).
Q: Which equation is correct: CO = HR x SV, or MAP = HR x EDV?
A: CO = HR x SV.
Q: According to the Frank-Starling mechanism, increasing venous return directly increases which variable?
A: Preload (which then increases stroke volume through greater stretch of the ventricular wall).
Q: Which factor would MOST increase ejection fraction?
A: Increased contractility (the ventricle empties more completely, lowering ESV and raising the SV/EDV ratio).
Q: Which factor would MOST decrease stroke volume?
A: Increased afterload (the ventricle cannot eject as completely against higher pressure, leaving more blood behind).
Q: A patient receives a β₁ agonist. Which response is expected?
A: Increased contractility (and increased heart rate).
Q: A patient receives a β₁ blocker. Which change is MOST likely?
A: Decreased contractility (and decreased heart rate).
Q: A patient receives atropine. Which response is MOST likely?
A: Increased heart rate (parasympathetic blockade removes vagal braking on the SA node).
Q: Which chamber generates the highest pressure during systole?
A: The left ventricle.
Q: A patient has EDV unchanged and ESV decreasing. What is the best explanation?
A: Increased contractility. The ventricle is emptying more completely at the same filling level.
Q: During moderate exercise, which variable increases first to help raise cardiac output?
A: Heart rate (via sympathetic activation and parasympathetic withdrawal).
Q: During strenuous exercise, which combination is most likely?
A: Increased CO, decreased TPR (vasodilation in active muscle beds lowers total peripheral resistance while cardiac output rises).
Q: Which change would MOST increase myocardial oxygen demand?
A: Increased afterload (forces the ventricle to do more work per beat).
Preload depends on venous return, which is covered in Part 3 (blood vessels and hemodynamics): the skeletal muscle pump, respiratory pump, and venous compliance all feed into how much blood comes back to the heart. Afterload is determined by arterial pressure and TPR, also covered in Part 3. The autonomic effects discussed here connect to baroreceptor reflex responses during haemorrhage and postural changes.
cardiac output, stroke volume, heart rate, ejection fraction, EDV, ESV, preload, afterload, contractility, inotropy, chronotropy, Frank-Starling mechanism, Starling's law, beta-1 agonist, beta-1 blocker, atropine, muscarinic antagonist, sympathetic stimulation, parasympathetic stimulation, vagal tone, left ventricle, left atrium, myocardial oxygen demand, ventricular function, cardiac performance, APK2105, anatomy and physiology, cardiovascular, UF