The heart pumps blood through the circulatory system and supplies the body with blood. Cardiac activity can be assessed with measurable parameters, including heart rate, stroke volume, and cardiac output. The cardiac cycle consists of two phases: systole, in which blood is pumped from the heart, and diastole, in which the heart fills with blood. The conduction system is made up of a collection of nodes and specialized conduction cells that initiate and coordinate the contraction of the myocardium. Pacemaker cells (e.g., sinus node) of the conduction system of the heart autonomously and spontaneously generate an action potential (AP). The conduction system transmits the AP throughout the myocardium, and the electrical excitation of the myocardium results in its contraction. A phase of relaxation (refractory period) prevents immediate reexcitation. The Frank-Starling mechanism maintains cardiac output by increasing myocardial contractility and thus stroke volume, in response to an increased preload (end-diastolic volume). The autonomic nervous system is able to regulate the heart rate as well as cardiac excitability, conductivity, relaxation, and contractility.
The main function of the heart is to maintain blood circulation and ensure blood supply to the body through its continuous pumping action. The heart's activity can be assessed using various parameters, including heart rate, stroke volume, and cardiac output.
Heart rate (HR)
- The number of heart contractions per minute (bpm)
- Normal heart rate at rest: 60–100 bpm
Stroke volume (SV)
- Volume of blood pumped by the left or right ventricle in a single heartbeat
- SV = end-diastolic volume (EDV) − end-systolic volume (ESV)
Ejection fraction (EF): the proportion of EDV ejected from the ventricle
- EF = SV / EDV = (EDV - ESV)/EDV
- Normally 50–70%
- Serves as an index of myocardial contractility: e.g., ↓ myocardial contractility → ↓ EF (seen in systolic heart failure, where EF is < 40%)
- Low in systolic heart failure and usually normal in diastolic heart failure
- Venous return: the rate at which blood flows back to the heart, which typically equals cardiac output (see also section on “Preload” below)
Cardiac output: the volume of blood the heart pumps through the circulatory system per minute (∼ 5 L/min at rest)
- Cardiac output (CO) = heart rate (HR) × stroke volume (SV)
- During physical activity (when SV becomes constant), an increase in cardiac output is mediated by increasing heart rate.
Via Fick principle
- Cardiac output is proportional to the quotient of the total body oxygen consumption and the difference in oxygen content of arterial blood and mixed venous blood.
- Cardiac output (CO) = oxygen consumption rate/arteriovenous oxygen difference = (O2 consumption)/(arterial O2content - venous O2 content)
- Via mean arterial pressure (MAP)
- Via Fick principle
- As HR increases, diastole is shortened, which decreases SV due to less filling time.
Increase in CO is achieved through a significant increase in HR and a slight increase in SV.
- The increased HR shortens the filling time (diastole), which limits the increase in SV.
- As the HR reaches ≥ 160/bpm, maximum CO is reached and begins to decrease, as SV declines faster than HR increases.
- During exercise, a healthy young adult can increase their CO by a factor of approx. 4–5 the resting rate of 5 L/min, i.e., to approx. 20–25 L/min.
- Cardiac index: cardiac output (L/min) in relation to body surface area (m2)
Volumetric flow rate
- Volume of blood that flows across a valve per second
Volumetric flow rate (Q) = average flow velocity (v) × cross-sectional area occupied by the blood (A)
- Amount of fluid entering the system must equal the amount leaving the system: Since Q1 = Q2,A1v1 = A2v2 (discharge at section 1 = discharge at section 2)
- Used to calculate flow across stenotic valves, vessels of different diameters, etc.
Myocardial oxygen demand
- Amount of oxygen required for optimal heart function
Depends mainly on four factors:
- Heart rate
- Wall tension (ventricular diameter)
- Receives drainage from most epicardial ventricular veins
- Contains majority of deoxygenated blood in the body
Cardiac blood pressures (measured via Swan-Ganz catheterization)
- Right atrium: < 5 mm Hg
- Right ventricle (pulmonary artery pressure): 25/5 mm Hg
- Left atrium (pulmonary capillary wedge pressure): < 12 mm Hg (higher than left ventricular pressure in mitral stenosis)
- Left ventricle: 130/10 mm Hg
Coronary perfusion pressure
- The driving pressure that forces blood into the coronary arteries during diastole
- Calculated as the difference in pressure between the aorta and left ventricle during diastole
The cardiac cycle can be divided into two phases: systole, in which blood is pumped from the heart, and diastole, in which the heart fills with blood. Systole and diastole are each subdivided into two further phases, resulting in a total of four phases of heart action. Depending on the phase, pressure and volume in the ventricles and atria change, with the pressure in the left ventricle changing the most and the pressure in the atria the least.
1.) Isovolumetric contraction
- Main function: ventricular contraction
- Follows ventricular filling
- Occurs in early systole, directly after the atrioventricular valves (AV valves) close and before the semilunar valves open (all valves are closed)
- Ventricle contracts (i.e., pressure increases) with no corresponding ventricular volume change
- LV pressure: 8 mm Hg → ∼ 80 mm Hg (when aortic and pulmonary valves open passively)
- LV volume: remains ∼ 150 mL
- RV pressure: 5 mm Hg → 25 mm Hg
- RV volume: ∼ 150 mL 
- The period of highest O2 consumption
2.) Systolic ejection
- Main function: Blood is pumped from the ventricles into the circulation and lungs.
- Follows isovolumetric contraction
- Occurs between the opening and closing of the aortic valve and pulmonary valve
- Ventricles contract (i.e., pressure increases) to eject blood, which decreases the ventricular volume
- Pressure: first increases from ∼ 80 mm Hg to 120 mm Hg and then decreases until aortic and pulmonary valves close
- Volume: ejection of ∼ 90 mL SV (150 mL → 60 mL)
3.) Isovolumetric relaxation
- Main function: ventricular relaxation
- Follows systolic ejection
- Occurs between aortic valve closing and mitral valve opening
- All valves closed (volume remains constant)
- Dicrotic notch: slight increase of aortic pressure in the early diastole that corresponds to closure of the aortic valve
- The ventricles relax (i.e., pressure decreases) with no corresponding ventricular volume change until ventricular pressure is lower than atrial pressure and atrioventricular valves open
- Pressure: decreases to ∼ 10 mm Hg in the left ventricle and ∼ 5 mm Hg in the right ventricle
- Volume: remains at ∼ 60 mL
Coronary blood flow peaks during early diastole at the point when the pressure differential between the aorta and the ventricle is the greatest.
- The coronary arteries fill with blood during diastole because they are compressed during ventricular systole.
4.) Ventricular filling
Main function: ventricles fill with blood
- Follows isovolumetric relaxation
- Occurs in early diastole; immediately after mitral valve opening
- Blood flows passively from the atria to the ventricles.
- The largest volume of ventricular filling occurs during this phase.
- Follows rapid filling
Occurs in late diastole; immediately before atrioventricular valves close
- LV pressure: ∼ 8 mm Hg; RV pressure: ∼ 5 mm Hg (2–8 mm Hg)
- LV and RV volume: ventricles fill with ∼ 90 mL (60 mL → 150 mL) 
During isovolumetric contraction and relaxation, all heart valves are closed. There are no periods in which all heart valves are open.
During states of increased heart rate (e.g., during exercise), the duration of diastole decreases so that there is less time for the coronary arteries to fill with blood and supply the heart with oxygen. Patients with narrow coronary arteries, e.g., due to atherosclerosis, will, therefore, experience chest pain (angina pectoris) during exertion.
Left ventricular pressure-volume diagram
- Used to: measure cardiac performance
- Shape: roughly rectangular; each loop is formed in a counter-clockwise direction
- (1) End-diastolic state: closure of the atrioventricular valve and the beginning of systole (the LV is filled with blood)
- (1 → 2) Isovolumetric contraction: With the atrioventricular and semilunar valves closed, contraction increases the internal pressure of the left ventricle; ventricular volume is left unchanged.
- (2) Opening of the semilunar valve when the ventricular pressure exceeds the aortic and pulmonary arterial pressure
- (2 → 3) Ejection phase: The ventricle pumps out the stroke volume.
- (3) Closure of the semilunar valve when the ventricular pressure falls below the aortic and pulmonary arterial pressure
- (3 → 4) Isovolumetric relaxation: the beginning of diastole, when the ventricle relaxes and all the valves are closed
- (4) Opening of the atrioventricular valve when the ventricular pressure falls below the atrial pressure
- (4 → 1) Filling phase: The ventricles receive blood from the atria and a new cardiac cycle begins.
Features of valvular diseases
|Valvular disease||Pressure-volume loop||Time-pressure curves|
|Mitral regurgitation|| || |
|Mitral stenosis|| || |
|Aortic regurgitation|| |
|Aortic stenosis|| || |
The width of the volume-pressure loop is the SV (the difference between EDV and ESV).
Conduction system of the heart
Definition: the collection of nodes and specialized conduction cells that initiate and coordinate contraction of the heart muscle
|Overview of the conduction system of the heart|
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|Bundle of His|| || || |
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Normal course of electrical conduction
- SA node (pacemaker) creates an action potential.
- Signal spreads across atria and causes their contraction.
- Signal reaches AV node and is slowed down.
- AV node conducts the signal to bundle of His down the interventricular septum to Purkinje fibers in myocardium.
- Purkinje fibers carry the signal across the ventricles.
- The ventricles contract (electromechanical coupling).
The electrical activity of the heart can be recorded through electrocardiography. See ECG for an overview of ECGs and their interpretation.
- Cardiac pacemaker cells (e.g., sinus node) of the conduction system of the heart autonomously and spontaneously generate an action potential (AP).
- The conduction system transmits the AP throughout the myocardium.
- The electrical excitation of the myocardium results in its contraction (see electromechanical coupling and filament sliding theory in muscle tissue).
- The phase of relaxation prevents immediate re-excitation (refractory period).
- Gap junctions are found in both pacemaker and contractile myocardial cells (not in skeletal muscle cells).
Cardiac calcium channels and calcium pumps
Direction of flow
Activation phase (affected tissue)
|L-type voltage-gated calcium channel|| || |
|T-type voltage-gated calcium channel|| || |
|Ryanodine receptor|| || |
|Calcium pumps|| |
SERCA (sarcoplasmic Ca2+-ATPase)
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The long plateau phase of the Ca2+ channels allows the myocardium to contract and pump blood effectively.
Other cation channels
All of these channels are located in the cell membrane.
|Name||Definition||Direction of flow||Activation phase (affected tissue)|
|Funny channels (HCN, If)|| || || |
Fast sodium channels (INa)
|Inward rectifier K+ channels|| || || |
|Delayed rectifier K+ channels(IKr and IKs)|| || |
Cardiac action potential
|Myocardial action potential (myocardium, bundle of His, Purkinje fibers)||Pacemaker action potential (SA node and AV node)|
(upstroke and depolarization)
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Pacemaker cells have no stable resting membrane potential. Their special hyperpolarization-activated cation channels (funny channels) ensure a spontaneous new depolarization at the end of each repolarization and are responsible for the automaticity of the heart conduction system. In sympathetic stimulation, more If channels open, increasing the heart rate.
Upstroke and depolarization of a pacemaker cell are caused by the opening of voltage-activated L-type calcium channels. In other muscle cells and neurons, upstroke and depolarization are caused by fast sodium channels.
The duration of action potentials differs in the various structures of the conduction system and increases from the sinus node to the Purkinje fibers.
Effective refractory period (ERP)
- Recovery period immediately after stimulation, during which a second stimulus cannot generate a new AP in a depolarized cardiomyocyte.
- Na+ channels are in an inactivated state until the cell fully repolarizes (phases 1–3).
- See “Refractory period” for details.
Phases (determined based on the number of sodium channels ready to be reactivated)
- Absolute refractory period: time interval in which no new AP can be generated because fast Na+ channels are deactivated (plateau phase)
- Relative refractory period: time interval in which some Na+ channels can be reactivated but have a higher threshold potential; only a strong impulse can trigger a new, low amplitude AP
- Supernormal period: period of supernormal excitability of the myocardium during repolarization (some parts of the heart are excited and others unexcited)
- Ensures sufficient time for chamber emptying (during systole) and refilling (during diastole) before the next contraction
- Prevents re-excitation of cardiomyocytes during this period to avoid circulatory excitation, which would lead to arrhythmia and tetany of cardiac muscle
The firing frequency of the SA node is faster than that of other pacemaker sites (e.g., AV node). The SA node activates these sites before they can activate themselves (overdrive suppression).
The plateau phase of the myocardial action potential is longer than the actual contraction. This allows the heart muscle to relax after each contraction and prevents permanent contraction (tetany).
Heterogeneity of the refractory period within the myocardium (in which some cells are in the absolute refractory period, relative refractory period, or resting potential state) renders individuals more susceptible to arrhythmias (e.g., ventricular fibrillation) when exposed to an inappropriately-timed stimulus.
During cardioversion, shock delivery must be synchronized with the R wave on ECG (indicating depolarization) and avoided during the relative refractory period (T waves, indicating repolarization).
Regulation of cardiac activity
Adaptation to short-term changes is provided by the Frank-Starling mechanism. Long-term changes in cardiac activity are regulated by the autonomic nervous system.
Definition: a law that describes the relationship between end-diastolic volume and cardiac stroke volume
Cardiac contractility is directly related to the wall tension of the myocardium.
- An increase in end-diastolic volume (preload) will cause the myocardium to stretch (↑ end-diastolic length of cardiac muscle fibers), which increases contractility (↑ force of contraction) and results in increased stroke volume in order to maintain cardiac output.
- This relationship between end-diastolic volume and stroke volume is shown in the Frank-Starling curve.
- Cardiac contractility is directly related to the wall tension of the myocardium.
Aim: maintain CO by modulating contractility and SV
- Stroke volume of both ventricles should remain the same.
Because the afterload is chronically increased in chronic hypertension, the left ventricle undergoes hypertrophy to decrease left ventricular wall stress (↑ LV wall thickness → ↓ LV wall stress).
An increase in preload leads to an increase in stroke volume; an increase in afterload leads to a decrease in stroke volume.
Autonomic innervation of the heart
- The autonomic nervous system is able to regulate heart rate, excitability, conductivity, relaxation, and contractility.
- Sympathetic fibers innervate both the atria and ventricles. Parasympathetic fibers only innervate the atria.
- Modulation of cardiac action by sympathetic and/or parasympathetic nerve fibers
- Function: long-term regulation of cardiac action
- Chronotropy: any influence on the heart rate
- Dromotropy: any influence on the conductivity of myocardium
- Inotropy: any influence on the force of myocardial contraction
- Lusitropy: any influence on the rate of relaxation of the myocardium
- Bathmotropy: any influence on the excitability of the myocardium
|Overview of autonomic innervation of the heart|
|Site of innervation||Nerves||Effect||Mechanism of action|
|Sympathetic stimulation|| || || || |
|Parasympathetic stimulation (e.g., stimulation of the cervix or the urinary and anal sphincters)|| || || |
Persistent epinephrine surges and long-lasting sympathetic activity can damage blood vessel endothelium, increase blood pressure, and increase the risk of heart attack and stroke.
Initially, a diminished ejection fraction can be compensated by increased sympathetic tone, RAAS activation, ADH release, and the Frank-Starling mechanism. In the long term, however, these mechanisms increase cardiac work and lead to heart failure. Antihypertensive drugs target these mechanisms.
Factors that affect cardiac output
- Preload: the extent to which heart muscle fibers are stretched before the onset of systole; depends on end-diastolic ventricular volume (EDV), which changes according to:
Afterload: the force against which the ventricle contracts to eject blood during systole
- Afterload is primarily determined by the mean arterial pressure (MAP) in the aorta, which is influenced by total peripheral resistance.
- ↑ Afterload → ↑ left ventricular pressure → ↑ left ventricular wall stress
According to Laplace's law, ↑ left ventricular pressure → ↑ left ventricular wall stress
- Left ventricular (LV) wall stress = (LV pressure × radius)/ (2×LV wall thickness)
Myocardial oxygen demand increases with HR, myocardial contractility, afterload, or diameter of the ventricle.