Cardiac Electrophysiology, Autonomic Control & The Cardiac Cycle

Electrical Conduction Pathway & Surface ECG

• Atria and ventricles are electrically isolated by the fibrous skeleton

  • Atrial myocytes cannot pass the action potential (AP) directly to ventricular myocytes.
  • 唯一的桥梁: Atrioventricular (AV) node
  • Receives the AP from the atria.
  • Introduces a deliberate pause (seen as the flat PR segment between the P-wave and QRS on the ECG).
  • Function of the pause:
    • Separates atrial depolarisation/contraction from ventricular depolarisation/contraction.
    • Ensures efficient ventricular filling before ejection.

• ECG waveforms & their meaning

  • P-wave  → atrial depolarisation.
  • PR segment  → AV-node pause/AV-node conduction delay.
  • QRS complex (always called "QRS" even if a Q or S deflection is absent)  → ventricular depolarisation.
  • T-wave  → ventricular repolarisation.

• Propagation pathway after the AV node

  1. AV node → Bundle of His.
  2. Bundle branches → apex.
  3. Purkinje fibres spread the impulse up the lateral ventricular walls.
  4. Contraction sequence: Interventricular septum ➔ apex ➔ lateral walls ➔ blood is squeezed from the bottom up toward the valves, simultaneously helping:
  • AV valves to close.
  • Semilunar valves to open once ventricular pressure exceeds arterial pressure.

Cardiac Action Potentials (APs)

• Every specialised tissue has its own AP configuration: SA node, AV node, bundle branches, Purkinje fibres, atrial myocytes, ventricular myocytes.
• For exam purposes focus on two prototypes:
  1. Pacemaker (SA-node) AP – automaticity model.
  2. Ventricular myocyte AP – working-muscle model.

1. SA-Node (Pacemaker) Action Potential

• Graph axes: time (ms) on x; membrane potential (mV) on y.
• Voltage range ≈ -60 \text{ mV} to +5 \text{ mV} (narrower than neuronal -70 to +30 \text{ mV}).
• Only 3 named phases (traditional numbering):
  • Phase 4 – Pacemaker (Resting) Potential
  • Unstable; membrane potential drifts upward because of Na⁺ leakage ("funny") channels.
  • Automaticity: slope of Phase 4 determines intrinsic heart rate; SA-node has the steepest slope ➔ fires first ➔ drives the whole heart.
  • Phase 0 – Depolarisation
  • Threshold (~-40 \text{ mV}) opens voltage-gated Ca²⁺ channels (not Na⁺!).
  • Ca²⁺ influx (charge +2) rapidly depolarises cell to ≈ 0 to +5 \text{ mV}.
  • Phase 3 – Repolarisation
  • Ca²⁺ channels close; voltage-gated K⁺ channels open; K⁺ efflux returns membrane to -60 \text{ mV}.
  • Ca²⁺ pumps/exchangers extrude the accumulated Ca²⁺.
• Key concept: Phase 4 governs rate; autonomic nerves tweak Phase 4 slope.

2. Ventricular Myocyte Action Potential

• Five phases (similar shape in atrial myocyte but shorter refractory period).

  1. Phase 4 – Resting (≈ -85 to -90 \text{ mV}).
  2. Phase 0 – Rapid Depolarisation
  • Opening of fast voltage-gated Na⁺ channels; Na⁺ rushes in.
  1. Phase 1 – Initial Repolarisation
  • Transient K⁺ outflow channels open briefly.
  1. Phase 2 – Plateau (Hallmark)
  • L-type Ca²⁺ channels open; Ca²⁺ influx balances K⁺ efflux.
  • Maintains depolarisation for \approx 250\text{–}300 \text{ ms} ➔ prolonged absolute refractory period.
  • Extra cytosolic Ca²⁺ prolongs cross-bridge cycling ➔ ↑ force of contraction (↑ contractility) and prevents tetany.
  1. Phase 3 – Repolarisation
  • Ca²⁺ channels close; delayed-rectifier K⁺ channels dominate ➔ return to Phase 4.

• Comparison summary

  • SA-node Phase 0 uses Ca²⁺; ventricular Phase 0 uses Na⁺.
  • SA-node lacks Phases 1 & 2; ventricular AP’s plateau is physiologically critical.

Autonomic Modulation of Automaticity & Contractility

Parasympathetic (Vagus, cranial nerve X)

• Innervation: SA node & AV node only.
• Neurotransmitter: Acetylcholine.
• Receptor: Muscarinic M₂.
• Cellular effect: Opens additional K⁺ channels during Phase 4 ➔ counters Na⁺ leak ➔ flattens Phase 4 slope.
• Physiological outcomes:
  • ↓ Rate of rise to threshold ➔ negative chronotropy (↓ heart rate).
  • Indirect ↓ contractility (fewer beats/min) but no direct effect on ventricular muscle.
  • Clinically termed the cardio-inhibitory pathway.

Sympathetic

• Innervation: SA node, AV node and ventricular myocardium.
• Neurotransmitter: Norepinephrine (plasma epinephrine mimics effect but arrives later).
• Receptor: β₁-adrenergic.
• Cellular effect: Via cAMP, opens additional Na⁺ (and Ca²⁺) channels during Phase 4 ➔ steepens Phase 4 slope.
• Physiological outcomes:
  • Reach threshold faster ➔ positive chronotropy (↑ HR).
  • ↑ Ca²⁺ entry in myocytes ➔ positive inotropy (↑ contractility).

Systole & Diastole – Timing and Definitions

• Pronunciation tips for clinical settings:
  • “di-AS-tə-lee” (diastole) / “siss-tə-lee” (systole).
  • Adjectives: diastolic, systolic.
• At resting HR ≈ 60 \text{ bpm}
  • Total cycle ≈ 1000 \text{ ms}.
  • Diastole ≈ \tfrac{2}{3} of cycle (≈ 666 \text{ ms}).
  • Systole ≈ \tfrac{1}{3} of cycle (≈ 334 \text{ ms}).
• Functionally:
  • Diastole: ventricles relaxed; filling from veins/atria.
  • Systole: ventricles contracting; ejecting blood into arteries.

Stroke Volume, Cardiac Output & Ejection Fraction

• Stroke Volume (SV): volume of blood pumped by one ventricle per beat.
  • \text{SV} = \text{EDV} - \text{ESV}
  • EDV (End-Diastolic Volume): volume in ventricle at end of filling (~"full").
  • ESV (End-Systolic Volume): volume remaining after ejection (“left-over”).
• Typical resting numbers (adult):
  • \text{HR} \approx 70\;\text{bpm}
  • \text{SV} \approx 70\;\text{mL/beat}
  • Cardiac Output (CO) = \text{HR} \times \text{SV} \approx 70 \times 70 = 4900\; \text{mL/min} \approx 5\; \text{L/min}.
• Ejection Fraction (EF) – size-independent index of pump function.
  • \text{EF}(\%) = \frac{\text{SV}}{\text{EDV}} \times 100
  • Example: \text{EDV} = 100\;\text{mL},\; \text{SV} = 70\;\text{mL} \Rightarrow \text{EF} = 70\% (upper-normal in young adults).
  • Clinical flags: \text{EF} < 50\% borderline; < 40\% = systolic heart failure.

The Wiggers (Cardiac Cycle) Diagram – A Guided Walk-Through

(Colour scheme in most textbooks: blue = diastole; tan/cream = systole.)

1. Pressure Curves

• Atrial pressure (blue): relatively low; small bump during atrial systole.
• Ventricular pressure (red): lowest in early diastole; rises steeply during ventricular systole (peaks ≈ 120 \text{ mmHg} on the left side).
• Aortic pressure (green): high throughout (pressure reservoir); systolic \approx 120\text{ mmHg} / diastolic \approx 80\text{ mmHg}.

2. Valve Events = Points Where Pressure Curves Cross

3. Isovolumetric Phases (all valves closed)

• Isovolumetric Contraction: AV closed (①) to semilunar open (②). Volume constant at EDV; ventricular pressure skyrockets.
• Isovolumetric Relaxation: Semilunar closed (③) to AV open (④). Volume constant at ESV; ventricular pressure plummets.

4. Changes in Ventricular Volume

1. Passive filling (both chambers in diastole) ≈ 80\% of EDV.
2. Atrial systole – “top-off” ≈ 20\% (waitress/coffee metaphor).
3. Isovolumetric contraction – volume plateau at EDV.
4. Ejection phase – volume falls toward ESV until semilunar valves close.
5. Isovolumetric relaxation – volume plateau at ESV before AV valves reopen.

5. Heart Sounds

• S1 (lub): Closure of AV valves at start of ventricular systole.
• S2 (dub): Closure of semilunar valves at end of systole.

Real-World & Clinical Connections

• Automaticity means the heart keeps beating without external commands; however, ANS & circulating catecholamines fine-tune HR and contractility to meet metabolic demand.
• Long refractory period (plateau) prevents tetanic contraction – an essential safety mechanism.
• β₁ blockers (e.g., metoprolol) flatten Phase 4 slope and shorten Phase 2 ➔ ↓ HR & ↓ contractility; used in hypertension, angina, arrhythmias.
• Digitalis (digoxin) increases intracellular Ca²⁺ during Phase 2 ➔ strengthens contraction; narrow therapeutic window, risk of toxicity.
• Heart failure classification uses EF; therapy aims to improve SV (via contractility) and/or lower afterload (pressure the ventricle must overcome).
• ECG PR-segment prolongation reflects excessive AV-node delay (first-degree AV block); QRS widening suggests bundle branch blocks or ventricular ectopy.
• Ethical dimension: understanding electrophysiology informs safe use of anti-arrhythmic drugs, defibrillation, and pacemaker implantation, directly impacting patient survival and quality of life.

Memorable Analogies & Metaphors from Lecture

• “AV node checks its papers”: emphasises the deliberate conduction delay.
• “Waitress topping up your coffee”: atrial systole adds the last 20 % to ventricular filling.
• “Rinse & repeat (shampoo bottle)”: cyclic nature of the cardiac cycle.

Equations & Numerical Nuggets to Memorise (LaTeX format)

• Resting voltage ranges:
  • Neuron: -70 \rightarrow +30 \text{ mV}
  • SA node: -60 \rightarrow +5 \text{ mV}
• Stroke volume: \boxed{\text{SV} = \text{EDV} - \text{ESV}}
• Cardiac output: \text{CO} = \text{HR} \times \text{SV}
• Ejection fraction: \boxed{\text{EF}(\%) = \frac{\text{SV}}{\text{EDV}} \times 100}
• Typical rest values: \text{HR} \approx 70\; \text{bpm},\; \text{SV} \approx 70\; \text{mL},\; \text{CO} \approx 5\; \text{L/min}
• Isovolumetric phases: no change in volume despite large pressure change ➔ “iso-” (same) “volumetric”.

Study Checklist

• Draw and label the SA-node & ventricular APs (identify channels per phase).
• Be able to sketch the Wiggers diagram and mark: valve closures/openings, isovolumetric periods, EDV, ESV, heart sounds.
• Calculate SV, CO, EF from given data.
• Predict autonomic effects on Phase 4 slope & describe resulting haemodynamic changes.
• Pronounce systole/diastole correctly in clinical conversation!