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Cardiac physiology

Last updated: April 20, 2021

Summarytoggle arrow icon

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 through its continuous pumping action. The heart's activity can be assessed using various parameters, including heart rate, stroke volume, and cardiac output.

Definitions

  • Heart rate (HR)
  • 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
  • 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.
    • Measurement
      • 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)
        • MAP = cardiac output (CO) × total peripheral resistance (TPR)
        • Mean arterial pressure (MAP) = systolic blood pressure (SP) + ⅔ diastolic blood pressure (DP) = (SP + 2 x DP)/3
    • 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.
  • 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:
  • Cardiac blood pressures (measured via Swan-Ganz catheterization)

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.

Systole

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 [1]
  • 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)

Diastole

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
  • 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 mL → 150 mL) [2]

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

Features of valvular diseases

Overview
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).

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
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

The electrical activity of the heart can be recorded through electrocardiography. See ECG for an overview of ECGs and their interpretation.

Overview

Cardiac calcium channels and calcium pumps

Overview
Name Definition Location

Direction of flow

Activation phase (affected tissue)

Calcium channels

L-type voltage-gated calcium channel
T-type voltage-gated calcium channel
  • During the middle of phase 4 in pacemaker cells (SA 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

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.

Overview
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

Cardiac action potential

Overview
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)
    • 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)
  • 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).

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

Overview

Definitions

  • 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
  • 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.

Overview of factors that affect cardiac output
Factors that increase SV Factors that decrease SV
Preload
Afterload
Myocardial contractility

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

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  2. Maceira AM, Prasad SK, Khan M, Pennell DJ. Reference right ventricular systolic and diastolic function normalized to age, gender and body surface area from steady-state free precession cardiovascular magnetic resonance.. Eur Heart J. 2006; 27 (23): p.2879-88. doi: 10.1093/eurheartj/ehl336 . | Open in Read by QxMD