Regulation of Heart Rate, Stroke Volume, and Cardiac Output

Cardiac Centers of the Medulla Oblongata

• Two nuclei clusters govern autonomic (ANS) influence on the heart.
• Cardioacceleratory center → sympathetic output.
• Cardio-inhibitory center → parasympathetic output.
• Location: posterior, superior medulla oblongata.
• Pathways
• Sympathetic fibers exit thoracic spinal cord, synapse in sympathetic chain ganglia, then travel as post-ganglionic cardiac nerves to
• SA node, AV node, conduction system, atrial + ventricular myocardium.
• Parasympathetic fibers are pre-ganglionic axons in cranial nerve X (vagus), synapse in cardiac plexus, then short post-ganglionic fibers innervate
• SA node, AV node, atrial musculature (minor ventricular influence).
• Functional outcome
• Sympathetic → ↑ beats / min (fight-or-flight).
• Parasympathetic → ↓ beats / min (rest-and-digest).

Pacemaker Potential & SA Node Autonomy

• SA (sinoatrial) and AV nodal cells possess intrinsic automaticity.
• Cannot hold a fixed resting membrane potential (~ −60 mV).
• After each repolarization, membrane “drifts” toward threshold (gradual Na⁺ leak ➔ “pacemaker potential”).
• SA node has the highest spontaneous rate (≈ 80–100 depol/min) → sets normal rhythm (“primary pacemaker”).
• Its impulse sweeps to AV node via internodal pathways sooner than AV node could self-depolarize.
• Graph characteristics (membrane potential vs. time):
• Upstroke: calcium-mediated depolarization.
• Downstroke: K⁺ efflux repolarization.
• Slow diastolic depolarization between action potentials.

Parasympathetic Modulation of the SA Node

• Neurotransmitter: acetylcholine (ACh) released at post-ganglionic terminals.
• ACh binds muscarinic receptors → opens K⁺ channels.
• Enhanced K⁺ efflux ➔ membrane hyperpolarizes & slope of diastolic depolarization flattens.
• Longer time to threshold ⇒ prolonged interval between action potentials.
• Net effect: ↓ HR (negative chronotropy).

Sympathetic Modulation of the SA Node

• Neurotransmitter: norepinephrine (NE) binds β₁-adrenergic receptors.
• Second-messenger cascade (cAMP) → opens Na⁺ & Ca²⁺ channels.
• Faster phase-4 depolarization, shortened repolarization time.
• Net effect: ↑ HR (positive chronotropy).
• Additional hormonal support: circulating epinephrine, thyroxine, etc.

Resting Heart-Rate Ranges & Terms

• “Normal” adult resting HR: ≈ 60–100 bpm (varies with age, fitness, health).
• Bradycardia: HR < 60 bpm. • Tachycardia: HR > 100 bpm.

Stroke Volume (SV) Concept & Pump Analogy

• Formula: SV=EDV−ESVSV = EDV - ESV
• EDV = end-diastolic volume (blood present after filling).
• ESV = end-systolic volume (blood remaining after ejection).
• Hand-pump metaphor:

  1. Raising handle ↓ cylinder pressure ➔ water enters (ventricular diastole, EDV).

  2. Depressing handle forces water out (ventricular systole, stroke volume).

  3. Residual water ≈ ESV.

Determinants of End-Diastolic Volume (EDV)

• Venous Return (VR)
• ↑ VR when
• Greater blood volume.
• Skeletal-muscle pump active (exercise compresses veins).
• Higher peripheral blood flow.
• ↓ VR during hypovolemia (bleeding, dehydration).
• Filling Time (duration of ventricular diastole)
• Inversely related to HR.
• ↓ HR → longer filling → ↑ EDV.
• ↑ HR → shorter filling → ↓ EDV.
• Preload (myocardial stretch before contraction)
• Directly proportional to EDV.
• Frank-Starling Law: “within physiological limits, the heart pumps all the blood it receives.” Greater stretch = stronger recoil = ↑ SV.

Frank-Starling Law & Sarcomere Length

• Optimal overlap of actin–myosin occurs at specific stretch lengths.
• Enhanced filling stretches sarcomeres toward optimum ➔
• ↑ tension development.
• ↑ ejection force.
• Outcome: ↑ EDV → ↓ ESV (because contractions are stronger) → ↑ SV.

Determinants of End-Systolic Volume (ESV)

• Contractility (inotropic state)
• Positive inotropes (↑ contractility → ↓ ESV → ↑ SV):
• Sympathetic stimulation (NE, epinephrine).
• Thyroxine, glucagon, digitalis.
• Negative inotropes (↓ contractility → ↑ ESV → ↓ SV):
• β-blockers (atenolol, propranolol).
• Ca²⁺-channel blockers (verapamil, diltiazem).
• Parasympathetic influence (mainly atria).
• Afterload (arterial resistance the ventricle must overcome)
• ↑ Afterload when
• Vasoconstriction, hypertension, aortic stenosis.
• Consequence: ventricles cannot eject as much blood → ↑ ESV → ↓ SV.
• ↓ Afterload (e.g., vasodilation) has opposite effect.

Integrated Control of Cardiac Output (CO)

• Master equation: CO=HR×SVCO = HR \times SV
• HR influencers
• ANS balance (sympathetic ↑, parasympathetic ↓).
• Body temperature (fever ↑, hypothermia ↓).
• Circulating hormones (epinephrine, thyroxine ↑).
• Physical conditioning (athletes often exhibit resting bradycardia but maintain high maximal CO).
• SV influencers
• EDV factors: venous return, filling time, preload.
• ESV factors: contractility, afterload.
• Exercise cascade example

  1. Skeletal-muscle contractions ↑ VR → ↑ EDV → ↑ preload → ↑ SV.

  2. Sympathetic discharge ↑ HR & contractility → ↓ ESV + ↑ HR.

  3. Combined effect: large rise in CO to match metabolic needs.

Pathophysiological Note: Heart Failure

• Occurs when CO cannot meet peripheral tissue demands.
• May stem from chronotropic or inotropic defects (HR or SV problems) or excessive afterload.
• Compensatory mechanisms (SNS activation, fluid retention) may initially sustain CO but often exacerbate workload & remodeling.

Key Numerical & Conceptual Recap

• SA node intrinsic rate: 80–100 bpm (modulated down by vagal tone at rest).
• Bradycardia < 60 bpm; tachycardia > 100 bpm.
• Typical adult EDV ≈ 120 mL; ESV ≈ 50 mL; SV ≈ 70 mL; resting CO ≈ 5 L / min.
• Fundamental equations
• CO=HR×SVCO = HR \times SV
• SV=EDV−ESVSV = EDV - ESV
• Effects summary
• ↑ Sympathetic: ↑ HR, ↑ contractility → ↑ CO.
• ↑ Parasympathetic: ↓ HR (minor ↓ contractility) → ↓ CO.
• ↑ Preload or ↓ Afterload: ↑ SV & CO.
• ↓ Blood volume or ↑ Afterload: ↓ SV & CO.