7.1 Cardiac Electrophysiology, ECG, and Mechanical Cardiac Cycle

7.1 Cardiac Electrophysiology, ECG, and Mechanical Cardiac Cycle

Understanding the precise integration between myocardial electrical activation and mechanical contraction is fundamental to cardiovascular physiology and clinical cardiology on the NPLEX Part I. The heart functions as a dual-pump system whose rhythmic performance relies on specialized pacemaker tissues, rapid conduction pathways, calcium-dependent excitation-contraction coupling, and coordinated pressure changes across cardiac chambers.

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Pacemaker Action Potentials (SA & AV Nodes)

Unlike contractile ventricular myocytes, cardiac pacemaker cells located within the Sinoatrial (SA) node (the primary physiological pacemaker) and Atrioventricular (AV) node possess automaticity—the ability to spontaneously generate action potentials without neural input. Their action potentials are characteristically non-rectangular, lacking a stable resting membrane potential.

Phases of the Pacemaker Action Potential

Note: Phases 1 and 2 are absent in pacemaker action potentials.

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Ventricular Cardiomyocyte Action Potentials

Contractile atrial and ventricular myocytes display a true resting membrane potential maintained near $-90\text{ mV}$ and generate rapid, long-duration action potentials consisting of five distinct phases (Phases 0 through 4).

Phases of Non-Pacemaker Action Potentials

1. Phase 0 (Rapid Upstroke): Voltage-gated fast $\text{Na}^+$ channels open rapidly in response to threshold depolarization, driving membrane potential toward $+20\text{ to }+30\text{ mV}$.
2. Phase 1 (Early Partial Repolarization): Fast $\text{Na}^+$ channels rapidly inactivate. Voltage-gated transient outward potassium channels ($I_{to}$) briefly open, causing minor $\text{K}^+$ efflux.
3. Phase 2 (Plateau Phase): Voltage-gated L-type $\text{Ca}^{2+}$ channels open, allowing slow inward $\text{Ca}^{2+}$ influx. This influx is balanced by outward $\text{K}^+$ efflux through delayed rectifier channels ($I_K$). Intracellular $\text{Ca}^{2+}$ influx triggers calcium-induced calcium release (CICR) from the ryanodine receptors (RyR2) of the sarcoplasmic reticulum, initiating muscular contraction.
4. Phase 3 (Final Repolarization): L-type $\text{Ca}^{2+}$ channels close while voltage-gated delayed rectifier $\text{K}^+$ channels remain open, driving rapid $\text{K}^+$ efflux to return membrane potential to baseline.
5. Phase 4 (Resting Membrane Potential): High resting permeability to $\text{K}^+$ via inward rectifier $\text{K}^+$ channels ($I_{K1}$) maintains a stable electrical baseline around $-90\text{ mV}$.

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Cardiac Conduction Pathway & Conduction Velocities

The electrical impulse originates in the SA node and travels sequentially through specialized cardiac tissues to ensure synchronized atrial and ventricular pumping:

1. SA Node: Rate of spontaneous depolarization determines heart rate (~60–100 bpm).
2. Atrial Internodal Pathways & Bachmann Bundle: Conducts depolarization rapidly across left and right atria (~1.0 m/s).
3. AV Node: Conduction velocity slows significantly to ~0.05 m/s. This physiological AV node delay (~0.1 seconds) allows complete atrial contraction and ventricular filling before ventricular systole begins.
4. Bundle of His & Bundle Branches: Rapid conduction down the interventricular septum.
5. Purkinje Fibers: Fastest conduction velocity in the heart (~4.0 m/s), facilitating immediate, synchronous depolarization of the entire ventricular myocardium from apex to base.

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Surface Electrocardiogram (ECG) Waveforms & Intervals

The surface ECG measures extracellular potential differences generated by cardiac electrical activity:

• P Wave: Represents atrial depolarization.
• PR Interval: Extends from onset of P wave to start of QRS complex (normal: 120–200 ms). Represents conduction time from SA node through AV node; prolonged in first-degree AV block.
• QRS Complex: Represents rapid ventricular depolarization (normal: <120 ms). Atrial repolarization occurs simultaneously but is masked by the high-voltage QRS complex.
• ST Segment: Isoelectric period corresponding to Phase 2 plateau phase of ventricular action potential. Elevated in transmural myocardial ischemia (STEMI) and depressed in subendocardial ischemia.
• T Wave: Represents ventricular repolarization.
• QT Interval: Extends from beginning of QRS complex to end of T wave; represents total duration of ventricular electrical depolarization and repolarization (electrical systole).

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Mechanical Cardiac Cycle Phases

The cardiac cycle alternates between systole (contraction/ejection) and diastole (relaxation/filling). Mechanical events are marked by pressure differentials causing valve opening and closure:

Phase 1: Isovolumetric Contraction (S1)
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Phase 2: Systolic Rapid & Reduced Ejection
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Phase 3: Isovolumetric Relaxation (S2)
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Phase 4: Rapid & Reduced Ventricular Filling (S3, S4)

1. Isovolumetric Contraction: Initiated by QRS complex. Ventricular pressure exceeds atrial pressure, causing immediate closure of mitral and tricuspid (AV) valves, generating the First Heart Sound (S1). All four cardiac valves remain closed; ventricular volume is constant at End-Diastolic Volume (EDV) (~120 mL).
2. Systolic Ejection: Ventricular pressure exceeds aortic and pulmonary arterial pressures, forcing aortic and pulmonic (semilunar) valves open. Rapid ejection transfers ~70% of stroke volume into great arteries, followed by reduced ejection as ventricular pressure wanes. Ventricular volume decreases to End-Systolic Volume (ESV) (~50 mL).
3. Isovolumetric Relaxation: Ventricular repolarization (T wave) causes ventricular pressure to fall below arterial pressure, triggering closure of aortic and pulmonic valves, producing the Second Heart Sound (S2). All four valves are closed; volume remains constant at ESV.
4. Ventricular Filling: Ventricular pressure drops below atrial pressure, causing AV valves to open. Early passive rapid filling occurs, during which an S3 heart sound may be heard (normal in young athletes, pathological in heart failure due to rapid filling into a dilated ventricle). Late diastole features atrial contraction ("atrial kick"), which contributes ~20–30% of EDV and may generate an S4 heart sound if contracting against a stiff, non-compliant ventricle (e.g., ventricular hypertrophy).

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Pressure-Volume (PV) Loops & Hemodynamic Parameters

A Left Ventricular Pressure-Volume Loop plots ventricular pressure against volume throughout one complete cardiac cycle:

• Stroke Volume (SV): $SV = EDV - ESV$ (normal ~70 mL).
• Cardiac Output (CO): $CO = HR \times SV$ (normal ~5 L/min at rest).
• Ejection Fraction (EF): $EF = \frac{SV}{EDV} = \frac{EDV - ESV}{EDV}$ (normal: 55%–70%).

Determinants of Cardiac Performance

• Preload: Degree of myocardial stretch prior to contraction, represented clinically by EDV or end-diastolic pressure. Increasing preload expands the PV loop rightward, increasing SV.
• Afterload: Resistance against which the ventricle must pump to eject blood, approximated by Mean Arterial Pressure (MAP). Increasing afterload increases ESV, reducing SV and narrowing the PV loop.
• Inotropy (Contractility): Intrinsic force of contraction at any given preload. Increased inotropy increases the slope of the End-Systolic Pressure-Volume Relationship (ESPVR), lowering ESV and elevating SV and EF.

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Autonomic Regulation & The Frank-Starling Mechanism

• Frank-Starling Law: Intrinsic cardiac property where increased EDV stretches ventricular myocytes toward optimal actin-myosin overlap, maximizing cross-bridge formation and generating a proportionately stronger force of contraction.
• Inotropy (Sympathetic Control): $\beta_1$-adrenergic receptor stimulation by norepinephrine/epinephrine activates $\text{G}_s$-protein $\rightarrow$ adenylyl cyclase $\rightarrow$ elevated $\text{cAMP} \rightarrow$ Protein Kinase A (PKA) activation. PKA phosphorylates L-type $\text{Ca}^{2+}$ channels (increasing inward $\text{Ca}^{2+}$ flux) and phospholamban (disinhibiting SERCA2a to accelerate SR $\text{Ca}^{2+}$ reuptake, enhancing relaxation rate/lusitropy).
• Chronotropy & Dromotropy: Sympathetic $\beta_1$ activation increases the Phase 4 slope of $I_f$ in the SA node (positive chronotropy) and speeds conduction through the AV node (positive dromotropy). Parasympathetic stimulation via Vagus nerve ($M_2$ muscarinic receptors) decreases cAMP, slows $I_f$ slope, opens acetylcholine-gated $\text{K}^+$ channels ($I_{K,ACh}$), and induces hyperpolarization, slowing HR and AV conduction.