Heart Rate and Stroke Volume Regulation Notes

Regulation of Heart Rate and Stroke Volume

Regulation of Heart Rate

  • Heart rate (HR) is initiated by autorhythmic cells and modulated by neural and hormonal input.
  • Adult resting HR is approximately 70 beats per minute (BPM).
  • Athletes often have lower resting HR due to higher stroke volume (SV).

Parasympathetic Nervous System (PNS) and Heart Rate

  • Acetylcholine (ACh) is the primary neurotransmitter of the PNS affecting heart rate.
  • ACh activates Cholinergic Muscarinic Receptors on the sinoatrial (SA) and atrioventricular (AV) nodes.
  • Effects on Ion Channels in Autorhythmic Cells:
    • Potassium (K) Channels:
      • Increased permeability to K+ (↑ K+ outflux).
      • ↓ Hyperpolarization.
      • Pacemaker potential starts at a more negative value.
      • Slows action potential firing rate.
    • Funny (If) Channels:
      • Reduced response to pacemaker potential.
      • Slows action potential firing rate.
    • Calcium (Ca) Channels:
      • Becomes less permeable (reduces cAMP).
      • ↓ Ca2+ influx.
      • Slows depolarization.
  • Overall effect: Delays the reach of the threshold, thus slowing the heart rate.

Sympathetic Nervous System (SNS) and Heart Rate

  • Catecholamines (e.g., epinephrine, norepinephrine) activate β1 receptors.
  • Activation of β1 receptors:
    • Activates the cAMP system.
    • Causes Ca2+ and If channels to remain open longer.
    • ↑ Permeability and transport properties of ion channels (Ca2+ and Na+).
    • ↑ Influx of Ca2+ and Na+.
    • ↑ Rapid depolarization, reaching threshold faster (faster AP).
    • ↑ Heart Rate.
  • cAMP System:
    • Activated by catecholamines.
    • Activates Adenyl Cyclase (AC).
    • AC produces cAMP from ATP.
    • cAMP activates Protein Kinase A (PKA).
    • PKA phosphorylates L-type Ca2+ channels & If channels.

Neurons Affecting the AV Node

  • Acetylcholine: ↑ AV node delay, ↓ conduction velocity through the AV node.
  • Catecholamines: ↓ AV node delay.
  • Catecholamines bind to β1 receptors.
  • Beta Blockers:
    • Drugs that block β receptors.
    • ↑ AV delay and ↓ conduction velocity.
    • β1 receptors are primarily in the Heart, while β2 receptors are found in the Lungs.
    • 1 Heart, 2 Lungs.

Regulation of Stroke Volume (SV)

  • SV is directly related to the force of contraction of cardiac muscle.
  • Force of contraction is affected by:
    • Muscle Fiber Length
    • Contractility of the Heart
Muscle Fiber Length
  • Refers to how much the fibers are stretched before contraction.
  • Proportional to the End-Diastolic Volume (EDV).
  • The more blood in the left ventricle, the more stretched the fibers will be.
  • Preload: The degree the sarcomere stretches before contraction.

Frank-Starling Curve

  • Illustrates the relationship between stretch (EDV) and force (SV).
  • X-axis: Represents EDV, reflecting sarcomere stretch.
  • Y-axis: Represents SV, reflecting contraction force.

Venous Return

  • EDV is determined by venous return.
  • Venous return depends on:
    • Skeletal Muscle Pump
    • Respiratory Pump
    • Sympathetic Innervation of Veins
    • Blood Volume
Skeletal Muscle Pump
  • Pumping of blood in veins by the muscles of the leg during contraction.
  • Sitting or standing still causes blood pooling.
Respiratory Pump
  • Pressure changes in the abdomen due to breathing.
  • Acts on the Inferior Vena Cava.
Sympathetic Innervation of Veins
  • Sympathetic activation causes constriction in veins (venoconstriction).
  • Venoconstriction: Smooth muscles are contracted, pushing more blood to the heart.
Blood Volume
  • High Blood Volume = High Blood Pressure (BP).
  • High BP = High Venous Return.
  • Affected by fluid consumption, urine volume (Renal Function), tissue fluid volume (Osmotic Pressure), and bleeding.

Contractility of the Heart

  • The ability of the heart to contract.
  • Influenced by Ca2+ interaction with filaments as it binds to troponin and determines the number of active cross-bridges.
  • ↑ Ca2+ = ↑ Contractility.
  • Inotropic Agents: Chemicals that affect the contractility of the heart.
    • Positive Inotropes: ↑ Contractility (Dopamine, Catecholamine, Glucagon, Insulin).
    • Negative Inotropes: ↓ Contractility (Beta Blockers, Calcium Channel Blockers, Antiarrhythmics).

Catecholamines as Positive Inotropes

  • Mechanism is similar to their effect on heart rate.
  • Catecholamines activate β1 receptors on contractile myocytes.
  • ↑ Intracellular cAMP activity.
  • ↑ Phosphorylation of voltage-gated Ca2+ channels.
  • Ca2+ channels stay open longer.
  • ↑ Influx of Ca2+.
  • ↑ Calcium in the sarcoplasmic reticulum.
  • ↑ Calcium binding to troponin (more active cross-bridges).
  • ↑ Contractility.

Glycosides as Positive Inotropes

  • Glycosides include digoxin.
  • Catecholamines depress the Na+/K+ channels.
  • Na+ accumulates in the cell.
  • ↓ Electrochemical-concentration gradient.
  • Cell unable to remove Ca2+ using the Ca2+-Na+ channel.
  • ↑ Ca2+ in the cell.
  • ↑ Calcium binding to troponin (more active cross-bridges).
  • ↑ Contractility.

Negative Inotropes

  • Decrease the contractility of the heart.
  • Beta Blockers:
    • Inhibit catecholamine’s inotropic pathway.
  • Calcium Channel Blockers (CCB):
    • Block Ca2+ channels in autorhythmic cells, reducing AP rate (negative chronotrope: reduce HR).
    • Also block L-type channels, slowing the conduction of impulse.