Regulation of Cardiac Function

What is cardiac output (CO)?

The volume of blood pumped out of the heart per minute.

What is the equation for cardiac output?

CO = heart rate × stroke volume (CO = HR × SV).

What is stroke volume (SV)?

The difference between end-diastolic volume (EDV) and end-systolic volume (ESV): SV = EDV − ESV.

What is EDV?

The volume of blood in the heart just before ventricular contraction.

What is ESV?

The volume of blood left in the ventricle after contraction, before refilling.

What is ejection fraction?

SV/EDV; the proportion of ventricular blood volume that is pumped out.

What are typical resting values for HR, EDV and ESV?

HR ≈ 70 BPM, EDV ≈ 120 mL, ESV ≈ 45 mL.

What is a typical resting stroke volume?

Approximately 75 mL (120 − 45 mL).

What is a typical resting cardiac output?

Approximately 5.25 L/min (70 × 75 mL/min).

How does cardiac output change during exercise?

It can increase from about 5 L/min at rest to approximately 20–25 L/min.

What happens to HR, EDV, ESV and SV during exercise?

HR increases, EDV increases, ESV decreases and SV increases.

What are the intrinsic factors affecting cardiac output?

Preload, afterload and inotropic state (contractility).

What are the extrinsic factors affecting cardiac output?

Neural input/neurotransmitters and hormones.

What is preload?

The degree of ventricular filling; EDV determines the preload on the heart.

What determines ventricular filling and therefore preload?

Filling pressure/venous return and filling time during diastole.

How does preload affect cardiac output?

Increased preload increases stroke volume and therefore cardiac output.

What is the Frank–Starling law?

As stretch on the heart increases, the force of contraction increases.

How does increased venous return affect cardiac contraction?

Increased venous return → increased ventricular filling/preload → increased stretch → greater force of contraction.

Why is the Frank–Starling mechanism important for balancing right and left ventricular output?

Extra blood entering the lungs increases LV filling, which increases LV contraction strength and helps clear the extra volume.

What is afterload?

The pressure that the ventricle must overcome in the arteries to eject blood.

What is left ventricular afterload?

Diastolic aortic pressure.

What happens when afterload increases?

Less blood is ejected, ESV increases, and at a given HR, SV and CO decrease.

How can chronic increased afterload affect the ventricular muscle?

The ventricular muscle hypertrophies, increasing ventricular wall thickness.

Why can ventricular hypertrophy caused by increased afterload be proarrhythmic?

More tissue area/volume provides more potential for re-entry.

What is the inotropic state?

The ionic basis of contraction; it relates to activation of contractile proteins by Ca²⁺.

What is contractility?

How well the ventricles can contract, including the speed, force and duration of contraction.

How does Ca²⁺ affect contractile force?

More Ca²⁺ activation produces more force; this is a positive inotropic influence.

Can different amounts of tension be generated at the same resting length?

Yes. Changing contractility allows different tension to be generated without changing resting length.

How can increased action potential duration increase contractile force?

Longer AP duration → more Ca²⁺ influx → greater Ca²⁺ loading → larger Ca²⁺ transients → greater force.

How does increased extracellular Ca²⁺ affect contractility?

Increased extracellular Ca²⁺ → more Ca²⁺ influx → increased Ca²⁺ loading → greater force.

How does decreased extracellular Na⁺ increase Ca²⁺ loading?

It reduces Ca²⁺ efflux, causing greater intracellular Ca²⁺ loading.

How does increased heart rate affect Ca²⁺ loading?

Increased rate causes Ca²⁺ accumulation/loading, increasing force.

What does sympathetic regulation do to the heart?

It increases heart rate and cellular force to meet increased demands.

Which autonomic neurotransmitter/receptor pathway is central to sympathetic cardiac stimulation?

Norepinephrine binds β₁ receptors.

What happens after norepinephrine binds to the β₁ receptor?

Gs α-subunit activates adenylate cyclase.

What does adenylate cyclase do during β₁ stimulation?

It increases cAMP production from ATP.

What does increased cAMP activate?

Protein kinase A (PKA).

What does PKA do?

It phosphorylates protein targets that alter cardiac function.

How does PKA phosphorylation of LTCCs affect the heart?

Enhanced LTCC (ICaL) → more robust calcium-induced calcium release (CICR).

How does PKA phosphorylation of RyRs affect contraction?

Enhanced RyR Ca²⁺ release → more robust CICR → larger Ca²⁺ transient → greater force.

How does PKA phosphorylation affect troponin sensitivity to Ca²⁺?

It decreases troponin sensitivity to Ca²⁺, promoting faster relaxation.

How does PKA phosphorylation affect phospholamban/SERCA?

Decreased phospholamban activity increases SERCA activity, increasing Ca²⁺ loading into the SR and producing a larger Ca²⁺ transient.

What are the main effects of sympathetic stimulation on cardiac function?

Increased heart rate, increased Ca²⁺ handling/force, and faster relaxation.

What does parasympathetic regulation do to the heart?

It slows heart rate and reduces cardiac output, helping reduce energy use and cardiac strain.

Which neurotransmitter mediates parasympathetic cardiac effects?

Acetylcholine (ACh).

Which receptor does ACh bind to in the heart?

Muscarinic M2 receptors.

What happens when M2 receptors are activated?

They activate Gi, which inhibits adenylate cyclase.

Which parts of the heart are mainly innervated by the parasympathetic system?

The atrial muscle and SA and AV nodes, with some ventricular innervation.

What is the main cardiac effect of parasympathetic stimulation?

Regulation of heart rate/pacing, mainly reducing rate.

Which parts of the heart does the sympathetic system innervate?

All parts of the heart.

What are the main cardiac effects of sympathetic stimulation?

Increased heart rate and increased contractility.

What happens when sympathetic nervous system activity increases?

Heart rate increases, producing tachycardia.

What happens when parasympathetic nervous system activity increases?

Heart rate decreases, producing bradycardia.

What happens to heart rate if autonomic nerves are severed?

Heart rate rises to about 110 BPM, the intrinsic SA node rate.

What does the intrinsic SA node rate demonstrate?

Humans have substantial basal vagal tone that normally suppresses the intrinsic pacemaker rate.

What are the key factors that allow cardiac output to adapt to body demands?

Changes in heart rate and stroke volume regulated by intrinsic mechanisms and autonomic control.