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CARDIAC OUTPUT

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1. DEFINITION

CO = Heart Rate (HR) × Stroke Volume (SV)

• CO = 5-6 L/min (average: 5.5 L/min)
• HR = 72 beats/min (adult resting)
• SV = 70-80 mL/beat
• Cardiac Index = CO / Body Surface Area = ~3.2 L/min/m²

Example calculation: EDV = 140 mL, ESV = 70 mL, HR = 75 bpm SV = 140 - 70 = 70 mL; CO = 70 × 75 = 5250 mL/min; Ejection Fraction = 70/140 = 0.50 (50%)

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2. DISTRIBUTION OF CARDIAC OUTPUT

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3. CONTROL OF CARDIAC OUTPUT

A. Control of Heart Rate (Extrinsic/Chronotropic Regulation)

(i) Cardiac Innervation

• Origin: Intermediolateral horn, spinal cord T1-T5
• Supply: SA node, AV node, atria and ventricles (epicardial fibers)
• Effects:
  • (+) Chronotropic - increases heart rate
  • (+) Inotropic - increases force of contraction
  • (+) Dromotropic - increases conduction velocity
  • (+) Bathmotropic - increases excitability

• Origin: Nucleus ambiguus in medulla; cell bodies in dorsal motor nucleus of vagus
• Supply: SA node, AV node, and atrial muscles only (endocardiac fibers); NO vagal motor fibers to ventricles
• Effects:
  • (-) Chronotropic - decreases heart rate (dominant resting effect = vagal tone)
  • (-) Dromotropic - decreases conduction velocity
  • (-) Inotropic - decreases atrial contractility only; does NOT influence ventricular contraction

(ii) Medullary Cardiac Centres

• Groups of neurons bilaterally in reticular formation of medulla (floor of 4th ventricle)
• Stimulation produces: vasoconstriction, increased BP, venoconstriction (increases VR), increased HR, increased myocardial contractility, increased peripheral resistance

• Neurons: dorsal motor nucleus of vagus + nucleus ambiguus + nucleus tractus solitarius
• Responsible for resting vagal tone via constant impulse discharge
• Stimulation: reduces heart rate (bradycardia)

• Baroreceptors: Solely responsible for resting vagal tone in a normally breathing individual
• Chemoreceptors: In hypoxia, produce marked hyperpnoea and bradycardia
• Corticohypothalamic descending pathways: Mediate emotional and cortical influences

(iii) Factors Affecting Heart Rate

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B. Control of Stroke Volume (Intrinsic Autoregulation)

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B1. HETEROMETRIC REGULATION (Frank-Starling Mechanism)

"The energy released by the cardiac muscle during contraction is proportional to the initial resting length of the muscle fibers (i.e., end-diastolic volume)."

• Preload = directly proportional to End-Diastolic Volume (EDV) = blood volume remaining in ventricles at end of diastole (normal EDV = 120-140 mL)
• Any factor that increases Venous Return (VR) → increases EDV → stretches myocardium → increases length of sarcomeres → more optimal actin-myosin overlap → greater force of contraction → greater stroke volume

1. Respiratory/Thoracic pump - inspiration creates negative intrathoracic pressure, compresses vena cava and right atrium, pulls blood toward heart
2. Cardiac pump - ventricular systole creates suction effect at venous end
3. Muscle pump - rhythmic skeletal muscle contraction compresses veins, propelling blood toward heart (valves prevent backflow)
4. Total blood volume - increased volume → increased VR
5. Capacity of venous system - venoconstriction decreases venous capacitance → increases VR
6. Body position - supine position increases VR (removes gravity); standing reduces it
7. Ventricular compliance - reduced compliance (stiff ventricle) limits filling

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B2. HOMOMETRIC REGULATION (Contractility-Based, Preload-Independent)

• Ventricles develop tension more rapidly
• Ejection of blood is faster
• Greater stroke volume for the same EDV (curve shifts up - see diagram above)

1. Catecholamines (epinephrine, norepinephrine) - via β1-adrenergic receptors → increase cAMP → increase Ca²⁺ entry
2. Sympathetic stimulation - same mechanism as catecholamines
3. Increased heart rate - within physiologic limits, ↑HR → ↑contractility (Bowditch effect / Treppe phenomenon)
4. Drugs:
   • Caffeine and theophylline - positive inotropic effect
   • Glucagon - increases cAMP formation
   • Digitalis (Digoxin) - inhibits Na⁺/K⁺-ATPase pump → ↑intracellular Na⁺ → ↑intracellular Ca²⁺ via Na⁺/Ca²⁺ exchanger → increases force of contraction (used in CHF)

1. Vagal stimulation - negative inotropic effect on atria
2. Intrinsic myocardial depression - as in heart failure
3. Myocardial infarction - fibrosis of myocardium → non-functional muscle
4. Hypercapnia, hypoxia, acidosis - metabolic depression
5. Drugs: Barbiturates

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4. MEASUREMENT OF CARDIAC OUTPUT

(i) Direct Fick Method

"The amount of a substance taken up by an organ per unit time equals the arterial concentration minus the venous concentration of that substance, multiplied by blood flow."

• Requires: arterial sample (aorta), mixed venous sample (pulmonary artery via catheter), and expired air O₂ measurement
• Gold standard for accuracy but invasive

(ii) Indicator Dilution Method

(iii) Echocardiography / Doppler

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5. CARDIAC OUTPUT IN SPECIAL STATES

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SUMMARY TABLE

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1. Heterometric regulation - Frank-Starling curve (CO vs EDV, showing effects of positive/negative inotropes)
2. Homometric regulation - Box diagram showing factors increasing/decreasing contractility at same preload
3. Cardiac innervation - Sympathetic (T1-T5) and parasympathetic (vagus/nucleus ambiguus) supply to SA node, AV node, atria, ventricles

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CARDIAC OUTPUT

10-Mark Answer | Physiology

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I. DEFINITION & NORMAL VALUE

Formula:

CO = Heart Rate (HR) × Stroke Volume (SV) = 72 beats/min × 70 mL = ~5040 mL/min

Normal Values:

Both ventricles pump equal outputs in the steady state. The outputs differ only transiently.

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II. REGULATION OF CARDIAC OUTPUT

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A. REGULATION OF HEART RATE

1. Cardiac Innervation

(a) Sympathetic Innervation

• Origin: Intermediolateral horn, spinal cord segments T1–T5
• Supply: SA node, AV node, atria and ventricles (epicardial fibers)
• Neurotransmitter: Norepinephrine → β₁-adrenergic receptors

(b) Parasympathetic (Vagal) Innervation

• Origin: Nucleus ambiguus and dorsal motor nucleus of vagus, medulla
• Supply: SA node, AV node, atrial muscles only - NO fibers to ventricles
• Neurotransmitter: Acetylcholine → muscarinic receptors

2. Medullary Cardiovascular Centres

• Located bilaterally in reticular formation of medulla (floor of 4th ventricle)
• Stimulation → vasoconstriction, ↑BP, venoconstriction (↑VR), ↑HR, ↑myocardial contractility

• Neurons: dorsal motor nucleus of vagus + nucleus ambiguus + nucleus tractus solitarius
• Tonically active → responsible for resting vagal tone
• Stimulation → bradycardia

• Baroreceptors (carotid sinus, aortic arch) - solely responsible for resting vagal tone
• Chemoreceptors - in hypoxia → bradycardia + hyperpnoea
• Corticohypothalamic pathways - mediate emotional/cortical effects

3. Other Factors Affecting Heart Rate

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B. REGULATION OF STROKE VOLUME

(Intrinsic Autoregulation - Two Mechanisms)

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B1. HETEROMETRIC REGULATION

(Frank-Starling / Starling's Law of the Heart)

"The more the cardiac muscle is stretched during diastole (up to a physiological limit), the greater is the force of contraction during systole."

• Preload ∝ End-Diastolic Volume (EDV)
• ↑ Venous Return → ↑ EDV → ↑ stretch of myocardium → ↑ sarcomere length → more optimal actin-myosin overlap → ↑ force of contraction → ↑ SV → ↑ CO

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Factors Affecting Venous Return (and hence Heterometric Regulation):

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B2. HOMOMETRIC REGULATION

(Contractility-Based / Preload-Independent)

• Ventricles develop tension more rapidly
• Ejection of blood is faster
• Greater SV for the same EDV → shifts Frank-Starling curve upward (positive inotropism) or downward (negative inotropism)

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III. METHODS OF MEASUREMENT OF CARDIAC OUTPUT

1. Direct Fick Method (Gold Standard)

"The amount of a substance taken up by an organ per unit time equals blood flow × (arterio-venous difference of that substance)."

• Requires: arterial sample (aorta) + mixed venous sample (pulmonary artery via right heart catheter) + expired air O₂ analysis
• Accurate but invasive

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2. Indicator Dilution Method

• A known amount of dye (e.g., Evans blue / indocyanine green) or cold saline is injected into a vein
• Concentration measured over time in arterial blood (Stewart-Hamilton equation)
• Thermodilution via Swan-Ganz catheter - most widely used clinical method

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3. Pulse Contour / Pulse Pressure Method

• CO estimated from the arterial pulse pressure waveform
• Less invasive; used in ICU monitoring

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4. Echocardiography (Doppler Method)

• Non-invasive
• CO = SV × HR
• SV calculated from: Aortic cross-sectional area × Velocity-Time Integral (VTI) of aortic flow
• Widely used clinically; no catheterization required

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5. Impedance Cardiography (ICG)

• Measures changes in thoracic electrical impedance during cardiac cycle
• Completely non-invasive; less accurate than Fick

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6. Radioactive Isotope Dilution

• Radioactive-labeled RBCs or albumin injected; dilution measured
• Research use; gives both CO and blood volume

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SUMMARY

Cardiac Output
├── Definition: Volume/ventricle/min = HR × SV
├── Normal: 5–6 L/min
│
├── Regulation
│   ├── A. Heart Rate (Extrinsic)
│   │   ├── Sympathetic (T1-T5): +chrono, +ino, +dromo, +bathmo
│   │   ├── Parasympathetic (Vagus/Nucleus ambiguus): -chrono, -dromo, -ino (atria)
│   │   ├── Medullary Centres (VMC + Vagal Centre)
│   │   └── Factors: Age, Sex, Temp, Hormones, Exercise, Pain
│   │
│   └── B. Stroke Volume (Intrinsic)
│       ├── Heterometric (Frank-Starling): EDV → stretch → force ↑
│       │   └── Factors affecting VR: Respiratory pump, Muscle pump,
│       │       Blood volume, Venous tone, Posture, Ventricular compliance
│       └── Homometric (Contractility): Independent of fiber length
│           ├── +ve Inotropes: Catecholamines, Digoxin, Caffeine, Glucagon
│           └── -ve Inotropes: Vagus, Hypoxia, MI, Barbiturates
│
└── Measurement
    ├── Fick Method (Gold standard - invasive)
    ├── Indicator dilution / Thermodilution (Swan-Ganz)
    ├── Echocardiography/Doppler (non-invasive)
    ├── Impedance cardiography
    └── Isotope dilution

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1. Frank-Starling curve (CO vs EDV - normal, +ve inotropic, -ve inotropic curves)
2. Heterometric regulation flow chart (VR → EDV → stretch → Starling → ↑CO)
3. Cardiac innervation diagram (sympathetic T1-T5 vs vagus/nucleus ambiguus; supply to SA, AV, atria, ventricles)

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CARDIAC OUTPUT

10-Mark Answer | Physiology

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I. DEFINITION & NORMAL VALUE

Formula:

CO = Heart Rate (HR) × Stroke Volume (SV) = 72 beats/min × 70 mL = ~5040 mL/min

Normal Values:

Both ventricles pump equal outputs in the steady state.

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II. REGULATION OF CARDIAC OUTPUT

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A. REGULATION OF HEART RATE

1. Cardiac Innervation

(a) Sympathetic Innervation

• Origin: Intermediolateral horn, spinal cord segments T1–T5
• Supply: SA node, AV node, atria and ventricles (epicardial fibers)
• Neurotransmitter: Norepinephrine → β₁-adrenergic receptors

(b) Parasympathetic (Vagal) Innervation

• Origin: Nucleus ambiguus and dorsal motor nucleus of vagus, medulla
• Supply: SA node, AV node, atrial muscles only - NO fibers to ventricles
• Neurotransmitter: Acetylcholine → muscarinic receptors

2. Medullary Cardiovascular Centres

• Located bilaterally in reticular formation of medulla (floor of 4th ventricle)
• Stimulation → vasoconstriction, ↑BP, venoconstriction (↑VR), ↑HR, ↑myocardial contractility

• Neurons: dorsal motor nucleus of vagus + nucleus ambiguus + nucleus tractus solitarius
• Tonically active → responsible for resting vagal tone
• Stimulation → bradycardia

• Baroreceptors - solely responsible for resting vagal tone
• Chemoreceptors - in hypoxia → bradycardia + hyperpnoea
• Corticohypothalamic pathways - mediate emotional/cortical effects

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3. FACTORS AFFECTING HEART RATE

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1. AGE

• After birth, as age increases → vagal tone increases → HR decreases
• In old age, vagal tone falls again → HR rises back up to ~100 bpm

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2. SEX (GENDER DIFFERENCE)

• Heart rate is slightly higher in females as compared to males
• Reason: lower vagal tone in females

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3. BODY TEMPERATURE

• For each 1°F rise in body temperature → HR increases by ~10 bpm
• Mechanism: direct effect on the SA node (heat increases automaticity)
• Vasodilatation also occurs → decrease in BP
• Fall in body temperature → decreases HR + vasoconstriction → BP rises

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4. EMOTIONAL STIMULI

• Mediated via corticohypothalamic pathways → sympathetic or parasympathetic activation

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5. EXERCISE

• HR increases in linearity with severity of exercise
• Mechanism: withdrawal of vagal tone initially, then sympathetic activation
• Hormones (epinephrine) released during exercise further increase HR

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6. PAINFUL STIMULI

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7. RESPIRATION (Sinus Arrhythmia)

• HR increases with inspiration
• HR decreases during expiration
• This phenomenon is called Sinus Arrhythmia
• Mechanism: During inspiration → negative intrathoracic pressure → ↑ venous return → stretch of RA → Bainbridge reflex → ↑ HR

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8. HORMONES

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9. DRUGS

• Digitalis → slows HR (slow, steady, but stronger beat - used in CHF)
• Drugs causing tachycardia: atropine, sympathomimetics
• Drugs causing bradycardia: beta-blockers, calcium channel blockers

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10. DISEASES

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B. REGULATION OF STROKE VOLUME

(Intrinsic Autoregulation - Two Mechanisms)

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B1. HETEROMETRIC REGULATION

(Frank-Starling / Starling's Law of the Heart)

"The more the cardiac muscle is stretched during diastole (up to a physiological limit), the greater is the force of contraction during systole."

• Preload ∝ End-Diastolic Volume (EDV)
• ↑ Venous Return → ↑ EDV → ↑ stretch of myocardium → ↑ sarcomere length → more optimal actin-myosin overlap → ↑ force of contraction → ↑ SV → ↑ CO

Factors Affecting Venous Return:

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B2. HOMOMETRIC REGULATION

(Contractility-Based / Preload-Independent)

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III. METHODS OF MEASUREMENT OF CARDIAC OUTPUT

1. Direct Fick Method (Gold Standard)

"The amount of a substance taken up by an organ per unit time equals blood flow × arterio-venous difference of that substance."

• Requires arterial + mixed venous (PA) samples + expired air analysis
• Accurate but invasive

2. Indicator Dilution Method

• Known amount of Evans blue dye or cold saline injected
• Concentration measured over time → Stewart-Hamilton equation
• Thermodilution via Swan-Ganz catheter = most used clinical method

3. Echocardiography / Doppler Method

• Non-invasive
• CO = SV × HR; SV = Aortic area × Velocity-Time Integral (VTI)

4. Impedance Cardiography (ICG)

• Measures changes in thoracic electrical impedance during cardiac cycle
• Completely non-invasive

5. Radioactive Isotope Dilution

• Radioactive-labeled RBCs injected; dilution measured
• Gives both CO and blood volume

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SUMMARY FLOWCHART

CARDIAC OUTPUT (5–6 L/min) = HR × SV
│
├── A. Heart Rate (Extrinsic)
│   ├── Sympathetic (T1-T5): +chrono/ino/dromo/bathmo
│   ├── Parasympathetic (Vagus): -chrono/dromo/ino (atria only)
│   ├── Medullary Centres (VMC + Vagal)
│   └── Factors (PDF):
│       Age | Sex | Body Temp | Emotional Stimuli
│       Exercise | Painful Stimuli | Respiration
│       Hormones | Drugs | Diseases
│
└── B. Stroke Volume (Intrinsic)
    ├── Heterometric (Frank-Starling): EDV → stretch → ↑ force
    │   └── VR factors: Resp pump, Muscle pump, Blood vol,
    │       Venous tone, Posture, Compliance
    └── Homometric (Contractility - preload independent)
        ├── +ve: Catecholamines, Digoxin, Caffeine, Glucagon
        └── -ve: Vagus, Hypoxia, MI, Barbiturates

MEASUREMENT:
Fick (gold standard) | Indicator dilution / Thermodilution
Echo-Doppler | Impedance cardiography | Isotope dilution

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1. Frank-Starling curve (CO vs EDV - three curves: normal, +ve inotropic, -ve inotropic)
2. Cardiac innervation diagram (Sympathetic T1-T5 vs Vagus/nucleus ambiguus)
3. Flow chart of factors affecting HR (10 factors from PDF)