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Cardiac physiology

Last updated: June 3, 2020


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 re-excitation. 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 task of the heart is to supply the body with blood. This activity can be assessed with measurable parameters, including heart rate, stroke volume, and cardiac output.


During exercise, a healthy young adult can increase their CO to approx. 4–5 times the resting rate of 5 L/min, to approx. 20–25 L/min. This 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 therefore reached and begins to decrease, as SV declines faster than HR increases.

Cardiac cycle

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 Hg25 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 atrium and ∼ 5 mm Hg in the right atrium
    • 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.

4.) Ventricular filling

Main function: ventricles fill with blood

Rapid filling

Reduced filling

  • 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 mL150 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

Physiological changes in valvular disease

Valvular disease Pressure-volume loop Time-pressure curves
Mitral regurgitation
Mitral stenosis
  • LA pressure > LV pressure during diastole
Aortic regurgitation
Aortic stenosis
  • LV blood pressure > aortic pressure during systole

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

Name Anatomic localization Characteristics Frequency

Sinoatrial node

ca. 60–80/min

Atrioventricular node

ca. 40–50/min
Bundle of His
  • Directly below the cardiac skeleton, within the membranous part of the interventricular septum
ca. 30–40/min

Purkinje fibers
  • Terminal conducting fibers in the subendocardium
  • Conduct cardiac AP faster than any other cardiac cells
  • Ensure synchronized contraction of the ventricles
  • Purkinje fibers have a long refractory period.
  • Form functional syncytium: forward incoming stimuli very quickly via gap junctions to allow coordinated contraction

ca. 30–40/min

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 downAV node conducts the signal to bundle of His down the interventricular septum to Purkinje fibers in myocardium → they 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.

Heart excitation


  1. Pacemaker cells (e.g., sinus node) of the conduction system of the heart autonomously and spontaneously generate an action potential (AP).
  2. The conduction system transmits the AP throughout the myocardium.
  3. The electrical excitation of the myocardium results in its contraction (see electromechanical coupling and filament sliding theory in muscle tissue).
  4. The phase of relaxation prevents immediate re-excitation (refractory period).

Cardiac calcium channels and calcium pumps

Name Definition Location

Direction of flow

Activation phase (affected tissue)

Calcium channels

L-type voltage-gated calcium channel (i Ca)
T-type voltage-gated calcium channel
  • During the middle of phase 4 (SV node)
Ryanodine receptor
  • Ca2+ channel that opens after binding of Ca2+ (i.e., calcium-induced Ca2+ release)
  • Membrane of SR
Calcium pumps

SERCA (sarcoplasmic Ca2+-ATPase)

  • Ca2+ pumps and exchangers that are responsible for terminating a contraction
  • Membrane of SR

Na+/Ca2+ exchanger

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)
  • Nonselective cation channels (e.g., for Na+, K+) in pacemaker cells that open as the membrane potential becomes more negative (hyperpolarized)
  • Extracellular → intracellular
  • Upstroke phase (sinus node)

Fast sodium channels (INa)

Potassium channels

Inward rectifier K+ channels
  • Intracellular → extracellular
Delayed rectifier K+ channels(IKr and IKs)
  • K+ channels that can be rapidly (IKr) or slowly (IKs) activated upon depolarization

The long plateau phase of the Ca2+ channels allows the myocardium to contract and pump blood effectively.

Cardiac action potential

Myocardial action potential (myocardium, bundle of His, Purkinje fibers) Pacemaker action potential (SA node and AV node)

Phase 0

(upstroke and depolarization)

Phase 1

(early repolarization)

  • Absent

Phase 2

(plateau phase)

  • Absent

Phase 3

(rapid repolarization)

  • Inactivation of voltage-gated Ca2+ channels
  • K+ efflux through delayed rectifier K+ channels continues: Persistent outflow of K+ exceeds Ca2+ inflow and brings TMP back to -90 mV.
  • The sarcolemmal Na+-Ca2+ exchanger, Ca2+-ATPase, and Na+-K+-ATPase restore normal transmembrane ionic concentration gradients (Na+ and Ca2+ ions return to extracellular space, K+ to intracellular space).
  • Closure of voltage-gated Ca2+ channels and
  • Opening of delayed rectifier K+ channels → K+ efflux (TMP returns to -60 mV)

Phase 4

(resting phase)

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!

Refractory period

  • Effective refractory period (ERP): a recovery period immediately after stimulation, during which a second stimulus cannot generate a new AP in a depolarized cardiomyocyte. The Na+ channels are in an inactivated state until the cell fully repolarizes (phases 1–3).
  • 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
  • Effect

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.

Frank-Starling mechanism

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.

  • Definition: 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
Site of innervation Nerves Effect Mechanism of action
Sympathetic stimulation
  • Fibers from the sympathetic cervical trunk (superior, middle, and inferior cardiac nerve)
  • Heart rate, conduction, contractility, and relaxation
Parasympathetic stimulation
  • Branches of the vagus nerve
    • Cervical cardiac branches
    • Thoracic cardiac branches

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

Factors that increase SV Factors that decrease SV
Myocardial contractility

Valsalva maneuver

Myocardial oxygen demand increases with an increase in HR, myocardial contractility, afterload, or diameter of the ventricle.


Clinical significance


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