Regulation of Cardiac Output Montemayor Monday Lecture 1

Regulation of Cardiac Output

Jennifer Montemayor, Ph.D.
Professor of Physiology
jmontemayor@rvu.edu
Matterhorn, Switzerland

Clinical Context

  • Case Presentation: A 31-year-old pregnant female, 34 weeks gestation, presents to her OB-GYN.

    • Symptoms: Increasing shortness of breath, swelling in legs.

    • Vital Signs:

      • Heart Rate (HR): 120 bpm

      • Respiratory Rate (RR): 20 breaths/min

      • Blood Pressure (BP): 100/60 mmHg

    • Physical Examination:

      • Detected an "opening snap" followed by a low-pitched diastolic murmur at the cardiac apex.

  • Diagnosis: Mitral Stenosis.

Pathophysiology of Mitral Stenosis

  • Listening Post: The mitral valve's listening post is located at the cardiac apex.

  • Heart Sounds:

    • Opening snap is produced by high left atrial pressure opening the mitral valve.

    • Low-pitched diastolic murmur results from turbulent flow across the stenotic mitral valve during ventricular diastole.

  • Effects on Cardiac Output:

    • Compromises left ventricle (LV) filling from left atrium (LA) to LV.

      • Resulting in decreased End-Diastolic Volume (EDV), Stroke Volume (SV), and Cardiac Output (CO), regardless of compensation mechanisms.

  • Catheterization Findings:

    • Right-sided cardiac catheterization would show elevated pulmonary capillary wedge pressure, indicative of increased left atrial pressure (LAP).

  • Pregnancy Demands:

    • Increased CO required during pregnancy, normally achieved through increased blood volume, HR, and SV.

    • Typical decrease in Total Peripheral Resistance (TPR) during pregnancy due to reduced hematocrit and hormone-mediated vasodilation.

    • Patient’s Mean Arterial Pressure (MAP) appears decreased due to reduced CO secondarily from mitral stenosis and decreased TPR.

    • Compensatory tachycardia is noted in the patient.

  • Investigations:

    • While shortness of breath and lower extremity swelling may be typical in pregnancy, further evaluations are necessary to determine if pulmonary edema and right heart complications have arisen due to mitral stenosis.

Foundational Basic Science Concepts to Understand

  • Key Questions Addressed:

    1. How is Heart Rate (HR) regulated to maintain CO?

    2. How is Stroke Volume (SV) regulated to maintain CO?

    3. What physiological maneuvers may support the diagnosis of a valvular murmur?

    4. How are changes in preload, afterload, and contractility represented on a Pressure-Volume (PV) loop?

    5. How are changes in total blood volume or inotropy represented on vascular and cardiac function curves?

Objectives

  1. Evaluate the mechanisms by which β1-adrenergic receptors mediate sympathetic effects on heart rate and conduction velocity.

  2. Evaluate the mechanisms by which M2-muscarinic receptors mediate parasympathetic effects on heart rate.

  3. Identify non-autonomic factors influencing heart rate and conduction velocity.

  4. Define:

    • Chronotropy: Rate of heart rhythm (HR).

    • Dromotropy: Speed of conduction through the heart.

    • Inotropy: Contractility of heart muscle.

    • Lusitropy: Rate of myocardial relaxation.

  5. Assess preload influence on CO and mechanisms by which it can increase or decrease.

  6. Analyze the influence of afterload on CO.

  7. Compare variables influencing EDV and End-Systolic Volume (ESV).

  8. Summarize the impact of contractility/inotropy on the end-systolic pressure-volume relationship and list positive and negative inotropic agents.

  9. Evaluate increased lusitropy's role in cardiac performance during exercise.

  10. Assess hemodynamic changes due to blood volume variations, venous tone adjustments, and inotropy as illustrated by cardiac and vascular function curves.

  11. Analyze hemodynamic changes in preload, afterload, and contractility reflected on pressure-volume loops, including predictions for PV loops in common clinical scenarios (valvular disorders, hypertension, etc.).

  12. Predict physiological maneuvers affecting preload or afterload and their effect on cardiac murmurs intensity (e.g., squatting, standing, Valsalva, amyl nitrate, hand grip).

Adrenergic and Cholinergic Receptors in the Heart

Regulation of Pacemaker Activity

  • Sympathetic and parasympathetic input modulate heart rate and conduction.

  • Factors influencing stroke volume and contractility.

Regulation of Cardiac Output

  • Key Formula:
    CO=HRimesSVCO = HR imes SV

  • Determinants of cardiac output via HR regulation and stroke volume regulation.

Autonomic Regulation of Cardiac Function

Mechanisms of Heart Rate Regulation (Chronotropy)

Cardiac Action Potential of Pacemaker Cells

  • Phase 0 (Depolarization): Inward Ca2+ current.

  • Phase 3 (Repolarization): Outward K+ current.

  • Phase 4 (Pacemaker Potential):

    • Increase inward “funny” current, Na+ influx.

    • Decrease outward K+ current.

    • Increase inward Ca2+ current.

Changes in Heart Rate

  • Changes in frequency of pacemaker firing affected by 3 mechanisms:

    • Rate of slow diastolic depolarization determines slope (Phase 4).

    • Maximum diastolic potential (Vm) and Threshold potential (TP) alterations influence firing frequency.

Sinoatrial Node Function

  • Parasympathetic (Vagal) Input:

    • Uses Acetylcholine → Cholinergic (M2-muscarinic receptors)

    • Effect: Negative chronotropy (↓ HR)

  • Sympathetic Input:

    • Norepinephrine → Adrenergic (β1-adrenoreceptors)

    • Effect: Positive chronotropy (↑ HR for approx. 200 bpm)

Sympathetic Nervous System Effects

  • Increases HR:

    • Mechanisms include increasing inward Ca2+ and slow depolarization rate.

  • Overall Result: Increases HR by decreasing the time to reach threshold potential.

Parasympathetic Nervous System Effects

  • Decreases HR:

    • Mechanisms include decreases in slow depolarization rate, increasing time required to reach firing threshold.

Changes in Conduction Velocity (Dromotropy)

  • Sympathetic Effects: Norepinephrine increases conduction velocity through increased depolarization rate.

  • Parasympathetic Effects: Acetylcholine decreases conduction velocity through a decrease in depolarization rate.

Regulation of Stroke Volume

Overview

  • Stroke Volume (SV): Volume of blood ejected in one heartbeat.

  • Formula:
    SV=EDV−ESVSV = EDV - ESV

  • Generally:

    • Stroke Volume (SV) increases with increased preload (EDV), increased contractility, and decreases with increased afterload.

Preload and End-Diastolic Volume (EDV)

  • Factors that Can Promote Increased Preload:

    1. Increased Central Venous Pressure (CVP)

    2. Decreased Heart Rate

    3. Increased Ventricular Compliance

    4. Increased Atrial Contractility

    5. Increased Afterload (not ideal)

    6. Pathological conditions.

Afterload

  • Definition: Peak systolic ventricular pressure that contracting fibers must overcome.

  • Effects of Increased Afterload:

    • Leads to increased ESV and decreased SV.

    • Example Conditions: systemic hypertension, stenotic heart valves.

Contractility/Inotropy

  • Definition: Force generated independently of EDV (preload).

  • Positive and Negative Inotropic Factors

    • Positive factors: Increase [Ca2+].

    • Negative factors: Decrease [Ca2+].

Summary of Factors Influencing Contractility

  • Positive Inotropic Agents: Include adrenergic agonists (e.g., catecholamines).

  • Negative Inotropic Agents: Include muscarinic agonists and ca2+ channel blockers.

Relaxation Rate (Lusitropy)

  • Concept: Refers to the diastolic function of ventricles.

  • Increased relaxation leads to improved diastolic filling time, essential during tachycardia.

Autonomic Effects on Heart Rate and Contractility

Autonomic Regulation

Effects

Sympathetic NS

↑ HR, ↑ conduction velocity, ↑ contractility

Parasympathetic NS

↓ HR, ↓ conduction velocity, ↓ contractility

Clinical Applications and Physiological Maneuvers

Impact on Preload and Afterload

  • Modifying Preload:

    • Decreasing preload through standing/Valsalva; increasing preload via squatting/passive leg raise.

  • Effect of Afterload Changes:

    • Usage of vasodilators decreases afterload; handgrip increases afterload.

Implications for Cardiac Murmurs

  • Rules of Thumb:

    • Increased preload generally increases flow through heart leading to murmur intensity change.

    • Various exceptions exist such as hypertrophic obstructive cardiomyopathy.

  • Afterload Effects:

    • Increasing afterload typically leads to increased intensity of back-flow related murmurs.

Changes to Pressure-Volume Loops

  • General Understanding:

    • Changes in preload, afterload, and contractility shift the pressure-volume (PV) relationship for the heart.

Independent Effects on PV Loops

  • Increased Preload: Causes increased end-diastolic volume (EDV), improved stroke volume.

  • Increased Contractility/Inotropy: Reflects a steeper slope in the end-systolic pressure-volume relationship (ESPVR).

  • Increased Afterload: Results in higher end-systolic volume and reduced stroke volume.

Changes to Vascular and Cardiac Output Function Curves

Vascular Function Curve Dependence

  • Influences: Shifts in blood volume and systemic filling pressure dictate the vascular function curve, with some adjustments caused by arteriolar constriction/dilation.

Key Relationships to Remember

  • Mean Arterial Pressure (MAP):
    MAP=COimesTPRMAP = CO imes TPR

  • Cardiac Output (CO):
    CO=HRimesSVCO = HR imes SV

  • Stroke Volume (SV):
    SV=EDV−ESVSV = EDV - ESV

  • Ejection Fraction (EF):
    EF=racSVEDVEF = rac{SV}{EDV}

  • Note: Additional relationships concerning filtration pressure are also important for comprehensive understanding.