Cardiac Electrophysiology and Heart Function

• Cardiac muscle structure and function are related to its energy demands.
• Heart's conduction system components and processes, including autonomic control, govern heart function
• Events of cardiac muscle contraction encompass refractory periods, plateau phase importance.
• Components of ECG readings can be described, identified, and their clinical significance discussed.
• Cardiac cycle stages and influencing factors detailed

Microscopic Structure of Cardiac Muscle

• Myocardium consists of cardiac muscle tissue.
• Cardiac muscle cells are short and branched and typically have one or two central nuclei.
• Endomysium (areolar connective tissue) supports cardiac muscle tissue.
• Invaginations of the sarcolemma (plasma membrane) form T-tubules, which extend into the sarcoplasmic reticulum.
• The sarcoplasmic reticulum surrounds myofilament bundles.
• Myofilaments are arranged in sarcomeres, giving cardiac muscle a striated appearance under a microscope.
• Optimal length (maximum overlap of filaments) occurs when the heart stretches due to blood filling the chamber, allowing for a strong contraction with more blood.

Intercellular Structures

• Sarcolemma folds at connections between cells.
• Intercellular structures enhance structural stability of the myocardium and facilitate communication between cells.
• Intercalated discs connect cells.
• Desmosomes mechanically join cells with protein filaments.
• Gap junctions electrically join cells, allowing ion flow and making each heart chamber a functional unit (functional syncytium).

Metabolism of Cardiac Muscle

• Cardiac muscle has a high demand for energy, necessitating an extensive blood supply and numerous mitochondria.
• Myoglobin and creatine kinase are present in cardiac muscle.
• Cardiac muscle can use fatty acids, glucose, lactic acid, amino acids, and ketone bodies as fuel.
• Cardiac muscle relies mostly on aerobic metabolism and is susceptible to failure when oxygen is low (ischemic) and interference with blood flow can cause cell death.

Heart's Conduction System

• The conduction system initiates and conducts electrical events.
• It ensures proper timing of contractions using specialized cardiac muscle cells, which have action potentials but do not contract.
• The activity of the conduction system is influenced by the autonomic nervous system.
• The sinoatrial (SA) node, or pacemaker, initiates the heartbeat and is located high in the posterior wall of the right atrium.
• The atrioventricular (AV) node is located in the floor of the right atrium.
• The atrioventricular (AV) bundle (bundle of His) extends from the AV node through the interventricular septum and divides into left and right bundles.
• Purkinje fibers extend from the left and right bundles at the heart's apex and course through the walls of the ventricles.

Innervation of the Heart

• The cardiac center of the medulla oblongata contains cardioacceleratory and cardioinhibitory centers.
• Baroreceptors and chemoreceptors in the cardiovascular system send signals, and the cardiac center sends signals via sympathetic and parasympathetic pathways.
• The cardiac center modifies cardiac activity, but does not initiate it; and influences the rate and force of heart contractions.
• Parasympathetic innervation decreases heart rate and starts at the medulla's cardioinhibitory center.
• Vagus nerves relay parasympathetic signals.
• The right vagus nerve innervates the SA node.
• The left vagus nerve innervates the AV node.
• Sympathetic innervation increases heart rate and force of contraction.
• Sympathetic signals start at the medulla's cardioacceleratory center.
• Neurons from segments T1–T5 of the spinal cord relay sympathetic signals.
• Sympathetic nerves extend to the SA node, AV node, myocardium, and coronary arteries.
• Coronary vessel dilation is increased by sympathetic innervation

Stimulation of the Heart

• Heart contraction has two events: the conduction system initiates and propagates an action potential, and the cardiac muscle cells initiate action potentials and contract.
• This process occurs first in the atria and then in the ventricles.

SA Nodal Cells at Rest

• SA nodal cells spontaneously depolarize and generate action potentials, initiating the heartbeat.
• Resting membrane potential (RMP) is about -60mV, but is unstable.
• Pacemaker potential enables cells to reach threshold without stimulation.
• The cells have many common membrane proteins like Na+/K+ pumps, Ca2+ pumps, and leak channels, plus specific slow voltage-gated Na+ channels, fast voltage-gated Ca2+ channels, and voltage-gated K+ channels.

Electrical Events at the SA Node

• SA node cells exhibit autorhythmicity (spontaneous firing).
• In reaching threshold, slow voltage-gated Na+ channels open, allowing Na⁺ to flow in and changing the membrane potential from –60 mV to –40 mV (threshold value).
• During depolarization, fast voltage-gated Ca2+ channels open to enable Ca2+ to flow in, changing the membrane potential from –40 mV to just above 0 mV.
• In repolarization, calcium channels close while voltage-gated K+ channels open so K+ flows out, returning the membrane potential to rest value (RMP = −60 mV).
• Voltage-gated Na+ channels open at –60 mV.
• One SA node action potential starts about 0.8 seconds after the last.
• This equals 75 beats per minute
• Inherently, the SA node would fire faster at 100 per minute
• Vagal tone (parasympathetic activity relayed by the vagus nerve) slows resting heart rate

Conduction System of the Heart

• Action spreads through the atria and reaches the AV node
• Excitation travels via gap junctions, enabling atria to contract together
• Action is delayed at the AV node because AV nodal cells are slow because of small diameter and few gap junctions
• Fibrous skeleton insulates except AV node (bottleneck)
• Delay allows ventricles to fill before they contract
• Action potential travels from AV bundle to bundle branches to Purkinje fibers
• Gap junctions then allow impulse to spread through cardiac muscles, the cells of the two ventricles contract nearly simultaneously.

Ventricle Specializations

• Purkinje fibers larger in diameter, action potential extremely rapid
• Ventricles contract at same time
• Papillary muscles stimulated to contract immediately
• Stimulation begins at heart apex, ensures blood efficiently ejected toward arterial trunks

Ectopic Pacemaker

• Conduction system cells other than SA node depolarize at slower rates than SA node
• AV node the default pacemaker at 40-50 beats/min
• Cardiac muscle at 20-40 beats/min is too slow to sustain life

Cardiac Muscle Cells at Rest

• Cardiac muscle cells contain Na+/ K+ pumps, Ca2+ pumps, leakage channels for Na⁺ and K+, and voltage-gated channels are closed.
• Have a resting membrane potential of -90 mV
• Contain specific voltage-gated channels, these are fast voltage-gated Na+ channels, slow voltage-gated Ca2+ channels, and voltage-gated K+ channels

Electrical Events of Cardiac Muscle Cells

• During depolarization triggered by impulse from conduction system, fast voltage-gated Na+ channels open.
• Na+ enters cell changing membrane potential from –90 mV to +30 mV
• Voltage-gated Na+ channels start to inactivate
• Depolarization opens voltage-gated K+ and slow voltage-gated Ca²+ channels
• K+ leaves cardiac muscle cell as Ca2+ enters
• Stimulates sarcoplasmic reticulum to release more Ca2+
• Membrane remains depolarized
• Voltage-gated Ca2+ channels close while K+ channels remain open • Membrane potential goes back to –90 mV

Events at the Sarcolemma

• Ca2+ enters sarcoplasm leading to contraction
• It binds to troponin and initiates crossbridge cycling
• Crossbridge formation, power stroke, release of myosin head, reset of myosin head
• Ca2+ levels decrease leading to relaxation as channels close and pumps move it into SR and out of cell

Repolarization and the Refractory Period

• Cardiac muscle cannot exhibit tetany
• Cardiac cells have a long refractory period and cannot fire a new impulse during this period
• Muscle cell plateau phase leads to refractory period of about 250 ms
• The heart cell contracts and relaxes before it can be stimulated again
• Makes tetanic contraction impossible

Electrocardiogram (ECG)

• Skin electrodes detect electrical signals of cardiac muscle cells
• P wave reflects electrical changes of atrial depolarization originating in SA node
• QRS complex is the electrical changes associated with ventricular depolarization, atria also simultaneously repolarizing
• T wave represents the electrical change associated with ventricular repolarization
• Segments between waves correspond to plateau phases of cardiac action potentials (no electrical change)
• Atrial depolarization recorded as the P wave.
• Atrial plateau recorded as PQ segment.
• Atrial repolarization is not visible on ECG
• Ventricular depolarization recorded as the QRS wave.
• Ventricular plateau recorded as ST segment.
• Ventricular repolarization recorded as T wave.

Electrical Events of the Heart and an ECG

• P-R interval equals time from start of P wave to the start of QRS deflection, from atrial depolarization to beginning of ventricular, and for action potential transmission through conduction system
• Q-T interval represents for QRS to the end of T wave, reflected ventricular action potentials, length depends on heart rate, changes may result in tachyarrhythmia

Clinical Arrhythmia

• Heart blocks impair conduction.
• First-degree AV block: PR prolongation: Slow conduction between atria and ventricles
• Second-degree AV block: Failure of atrial action potentials to reach ventricles
• Third-degree AV block: Failure of all action potentials to reach ventricles
• Atrial fibrillation: chaotic timing of atrial action potentials
• Ventricular fibrillation: chaotic electrical activity, uncoordinated contraction and pump failure
• Treated with defibrillator

Cardiac Cycle

• The cardiac cycle involves all events from the start of one heartbeat to the start of the next.
• It includes both systole (contraction) and diastole (relaxation).
• Contraction increases pressure and relaxation decreases pressure, moving blood down its pressure gradient (high to low).
• Valves prevent backflow.
• Ventricular contraction raises ventricular pressure, pushing AV valves closed and semilunar valves pushed open ejecting blood to artery
• lowers ventricular pressure, semilunar valves close.
• Atrial blood pressure forces AV valves open and blood flows into ventricles.

Phases of Cardiac Cycle

Four chambers at rest:

• Blood returning to both atria
• Passive filling of ventricles
• Atrial contraction and ventricular filling fills ventricles to end-diastolic volume (EDV)
• Purkinje fibers then initiate ventricular excitation, ventricles contract, ventricular pressure is still less than arterial trunk pressure, so semilunar valves still closed Ventricles continue to contract:
• Semilunar valves forced open as blood moves from ventricles to arterial trunks (stroke volume SV)
• End systolic volume (ESV) is amount of blood remaining in ventricle
• Isovolumic relaxation: Arterial pressure greater than ventricular pressure blood closes semilunar valves, ventricles relax
• Atrial relaxation and ventricular filling chambers all are relaxed with greater Atrial pressure

Ventricular Balance

• Left heart pumps must be stronger than right heart with equal blood pumped by both sides
• But ejected blood volumes must be the same or edema (swelling) can occur

Cardiac Output

• HR × SV = CO
• Maintain resting CO, individuals with smaller hearts larger stroke volume and slower heart rate
• Capacity to increase cardiac output above rest level, gives measure of level of exercise an individual can pursue • Chronotropic agents change heart rate, via autonomic nervous system or hormones

Positive Chronotropic Agents

• Sympathetic nerve stimulation causes NE release on heart
• NE and EPI bind to nodal cells to the beta-one adrenergic receptors. G-protein, adenylate cyclase, cAMP, protein kinase cascade
• Thyroid increases receptors on nodal cells
• Caffeine inhibits cAMP breakdown, while nicotine and cocaine release and inhibit reuptake of norepinephrine
• Negative chronotropic agents decrease heart rate
• Parasympathetic activity releases acetylcholine (ACh) onto nodal cells, and ACh binds muscarinic receptors which open K+ channels to making it more negative

Autonomic Reflexes

• Baroreceptors and chemoreceptors send signals to cardiac center
• Autonomic reflexes influence sympathetic and parasympathetic systems as needed.
• Atrial reflex (Bainbridge reflex) protects heart from overfilling.

Variable Influence on Stroke Volume

• Affected by venous return (volume), inotropic agents, and pressure
• As EDV increases, the greater stretch of heart wall results in more optimal overlap, Frank-Starling law
• Heart contracts when filled with blood: high-caliber athletes with strong hearts
• Inotropic agents change stroke volume
• Afterload affects arteries from ventricles, seen more as you age

Test your knowledge of cardiac electrophysiology, action potentials in the SA and AV nodes, and ECG interpretation. Questions cover the plateau phase, AV node function, regulation of heart rate by the autonomic nervous system, and indicators of myocardial ischemia.