Learning Objectives

By the end of this section, learners will be able to:

1. Define the determinants of stroke volume and cardiac output
2. Explain how preload, afterload, and contractility affect ventricular performance
3. Describe the cellular mechanisms regulating myocardial contractility
4. Apply Laplace’s law to understand wall tension, wall stress, and cardiac remodeling
5. Relate cardiac physiology to common clinical and pharmacologic scenarios

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Stroke Volume (SV)

Stroke volume is the amount of blood ejected by the ventricle with each heartbeat.

Three primary factors determine SV:

• Contractility
• Preload
• Afterload

Mnemonic: SV = CAP (Contractility, Afterload, Preload)

Stroke Volume Increases With:

• ↑ Contractility (e.g., exercise, anxiety, sympathetic stimulation)
• ↑ Preload (e.g., early pregnancy, increased venous return)
• ↓ Afterload

Stroke Volume Decreases With:

• ↓ Contractility
• ↓ Preload
• ↑ Afterload

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Stroke Work (SW)

Stroke work represents the mechanical work performed by the ventricle to eject one stroke volume.

$Latex \textbf{Stroke Work (SW) = SV × Mean Arterial Pressure (MAP)}Latex

• A failing heart exhibits ↓ SV due to systolic and/or diastolic dysfunction, resulting in reduced stroke work.

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Contractility

Contractility refers to the intrinsic ability of cardiac muscle to generate force independent of preload and afterload.

Contractility (and SV) Increases With:

• Catecholamine stimulation (β₁-receptor activation):
  • ↑ cAMP → activation of protein kinase A (PKA)
  • PKA phosphorylates phospholamban → ↑ Ca²⁺ ATPase activity
  • ↑ Ca²⁺ storage in the sarcoplasmic reticulum
  • PKA phosphorylates L-type Ca²⁺ channels → ↑ Ca²⁺ entry
  • ↑ Ca²⁺-induced Ca²⁺ release
• Increased intracellular Ca²⁺
• Digoxin:
  • Inhibits Na⁺/K⁺ ATPase
  • ↑ intracellular Na⁺ → ↓ Na⁺/Ca²⁺ exchanger activity
  • ↑ intracellular Ca²⁺ → ↑ contractility

Contractility (and SV) Decreases With:

• • β₁-blockade (↓ cAMP)
  • Heart failure with systolic dysfunction
  • Acidosis
  • Hypoxia or hypercapnia (↓ PaO₂ / ↑ PaCO₂)
  • Non-dihydropyridine Ca²⁺ channel blockers

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Preload

Preload is approximated by ventricular end-diastolic volume (EDV).

It depends on:

• Venous tone
• Circulating blood volume
• Venous return

Clinical Correlation:

• Venous vasodilators (e.g., nitroglycerin) ↓ preload by reducing venous return.

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Cardiac Oxygen Demand

Myocardial oxygen demand increases with:

• ↑ Contractility
• ↑ Afterload (proportional to arterial pressure)
• ↑ Heart rate
• ↑ Ventricular diameter (↑ wall tension)

The coronary sinus contains the most deoxygenated blood in the body.

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Wall Tension and Laplace’s Law

According to Laplace’s law:

$$\text{Wall tension = Pressure × Radius}$$ $$\text{Wall stress = (Pressure × Radius) ÷ (2 × Wall thickness)}$$

• Increased ventricular pressure or radius → ↑ wall tension
• Increased wall thickness → ↓ wall stress

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Afterload

Afterload is approximated by mean arterial pressure (MAP).

Effects of Increased Afterload:

• ↑ Pressure → ↑ wall tension (Laplace’s law)
• ↑ Wall tension → ↑ myocardial oxygen demand
• ↓ Stroke volume

Adaptation:

• The left ventricle compensates by hypertrophy, increasing wall thickness to reduce wall stress.

Clinical Correlations:

• Arterial vasodilators (e.g., hydralazine) ↓ afterload
• ACE inhibitors and ARBs ↓ both affect preload and afterload
• Chronic hypertension (↑ MAP) leads to left ventricular hypertrophy

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Activity