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Coronary Circulation

1. Anatomical Overview

Left Coronary Artery (LCA)

• Supplies the anterior and left lateral portions of the left ventricle
• Divides into the left anterior descending (LAD) branch and the left circumflex branch

Right Coronary Artery (RCA)

• Supplies most of the right ventricle
• Also supplies the posterior left ventricle in 80-90% of people ("right dominant" circulation)

Coronary Venous Drainage

• About 75% of left ventricular venous blood returns via the coronary sinus to the right atrium
• Most right ventricular blood returns through anterior cardiac veins directly into the right atrium
• A small amount drains via Thebesian veins (vv. cordis minimae), which empty directly into all four cardiac chambers
• Additionally, arteriosinusoidal vessels connect arterioles to chambers, and arterioluminal (arterio-luminal) vessels are small arteries draining directly into chambers

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2. Normal Coronary Blood Flow

• At rest: approximately 70 mL/min/100 g of heart weight, or about 225 mL/min total
• This equals roughly 4-5% of total cardiac output
• Coronary blood flow per gram is typically higher in women than in men
• During strenuous exercise, coronary flow increases 3-4 fold to meet the heart's increased oxygen demands (while cardiac work may increase 6-9 fold, making efficiency more important)

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3. Epicardial vs. Subendocardial Perfusion

• It bears the highest wall stress
• Its perfusion is most compromised during systole
• The extra vessels of the subendocardial plexus must compensate - any imbalance leads to subendocardial ischemia, which is the most common site of myocardial infarction

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4. Phasic Nature of Coronary Blood Flow

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5. Factors That Alter Coronary Blood Flow

A. Local Metabolic Factors (Primary Regulators)

• ~70% of oxygen delivered by coronary blood is extracted at rest (compared to ~25% in other tissues)
• This leaves almost no O2 reserve, so the only way to increase O2 delivery is to increase flow
• When O2 consumption rises (increased contractility, heart rate, wall stress), local tissue hypoxia triggers arteriolar vasodilation (active hyperemia)
• When O2 supply falls (reduced flow), reactive hyperemia restores flow after occlusion ends

• The most potent vasodilator in the coronary circulation
• When increased cardiac work depletes ATP → ATP → ADP → AMP → adenosine
• Adenosine diffuses out of cardiac cells and causes profound coronary arteriolar dilation
• Also the mechanism behind reactive hyperemia: adenosine accumulates during the ischemic period and causes a surge in flow once compression ends

• CO2 accumulation, H⁺ (lactic acidosis), decreased O2 tension
• Prostaglandins (particularly prostacyclin, PGI₂ - a vasodilator)
• Nitric oxide (NO) from endothelium - tonic vasodilation

These metabolic factors override all other control mechanisms. Even if nervous stimulation tends to constrict coronary vessels, metabolic vasodilation overcomes that vasoconstriction within seconds.

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B. Aortic Diastolic Pressure (Perfusion Pressure)

• Since the left coronary artery fills almost entirely in diastole, the aortic diastolic pressure is the key perfusion pressure
• Reduced aortic diastolic pressure (e.g., aortic regurgitation, severe hypotension, shock) directly reduces coronary perfusion
• Elevated diastolic pressure (e.g., hypertension) increases coronary driving pressure

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C. Heart Rate

• Tachycardia reduces left coronary flow by shortening diastole (the filling period)
• At high heart rates, less time is available for left ventricular diastolic filling, reducing net coronary flow
• This is especially significant when combined with increased O2 demand (exercise) or coronary stenosis

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D. Intramyocardial / Extravascular Compression

• Ventricular wall tension during systole compresses intramural coronary vessels
• Greater wall tension = greater compression = greater impedance to flow
• Increased preload (higher LVEDV), increased afterload (aortic stenosis, hypertension), and hypertrophy all increase wall tension and worsen subendocardial perfusion

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E. Autonomic Nervous System

• Direct effect: Epicardial coronary arteries have predominantly alpha-1 receptors (vasoconstriction); intramuscular arteries have more beta-2 receptors (vasodilation). Net direct effect is mild vasoconstriction
• Indirect (dominant) effect: Sympathetic activation increases heart rate and contractility → raises O2 demand → triggers metabolic vasodilation that far outweighs the direct constrictor effect
• Net result: sympathetic stimulation increases coronary flow overall via metabolic override
• In some individuals, disproportionate alpha vasoconstriction causes vasospastic angina

• Direct effect: acetylcholine causes direct coronary vasodilation
• Indirect effect: slows heart rate and slightly depresses contractility → reduces O2 consumption → indirectly reduces flow
• Net effect: vagal stimulation mildly reduces coronary flow (indirect dominates)

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F. Coronary Perfusion Pressure (Autoregulation)

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G. Cardiac Metabolism and Substrates

• At rest, the heart derives ~70% of its energy from fatty acid oxidation
• Under ischemia/hypoxia, the heart shifts to anaerobic glycolysis - much less efficient, produces lactic acid
• The increased demand for glucose and accumulation of lactate/H⁺ further stimulates vasodilation

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H. Pathological Factors

• Coronary artery stenosis: A fixed stenosis limits maximal vasodilatory reserve. Patients may be asymptomatic at rest (autoregulation compensates) but develop ischemia on exertion when flow demand exceeds the limited maximum supply
• Coronary vasospasm: Abnormal alpha-adrenergic or endothelin-mediated constriction (Prinzmetal/variant angina)
• Increased venous pressure (heart failure): Reduces the pressure gradient across the coronary bed
• Aortic valve stenosis: Left ventricular systolic pressure must greatly exceed aortic pressure to eject blood, which both compresses coronary vessels more severely and increases O2 demand

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Summary Table

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• Guyton and Hall Textbook of Medical Physiology, Chapter 21 (Coronary Circulation)
• Ganong's Review of Medical Physiology, 26th Ed., Chapter 33
• Costanzo Physiology, 7th Edition (Coronary Circulation section)

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Coronary Circulation and Factors Affecting Coronary Blood Flow

Introduction

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Anatomical Considerations

Arterial Supply

• Arises from the left aortic sinus
• Divides almost immediately into:
  • Left Anterior Descending (LAD) - supplies the anterior left ventricle, anterior interventricular septum, and apex
  • Left Circumflex (LCx) - supplies the lateral and posterior left ventricle
• Supplies the anterior and left lateral portions of the left ventricle

• Arises from the right aortic sinus
• Supplies most of the right ventricle
• Supplies the posterior left ventricle in 80-90% of individuals (right dominant circulation)
• Gives off the posterior descending artery (PDA) in right dominant hearts

• Right dominant: 80-90% (RCA gives PDA)
• Left dominant: 10-15% (LCx gives PDA)
• Co-dominant: 5%

Coronary Venous Drainage

Anatomical Layers of Coronary Vasculature

• Epicardial coronary arteries: Large conduit vessels on the heart surface; act as capacitance vessels; site of atherosclerosis
• Intramuscular arteries: Penetrate from epicardium into myocardium; primary resistance vessels
• Subendocardial arterial plexus: Lies immediately beneath the endocardium; most vulnerable to ischemia

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Normal Coronary Blood Flow

• At rest: 70 mL/min/100 g heart weight, total approximately 225 mL/min
• Represents 4-5% of resting cardiac output
• At rest: approximately 70% of delivered oxygen is extracted (cf. ~25% in other tissues)
• This near-maximal extraction means the only mechanism to increase O2 delivery is to increase flow
• During maximal exercise: flow increases 3-4 fold

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Phasic Nature of Coronary Blood Flow

• During systole: LV intramyocardial pressure (121 mmHg) slightly exceeds aortic pressure (120 mmHg) → pressure gradient reverses → flow falls to near zero or briefly reverses
• During diastole: Aortic pressure (80 mmHg) greatly exceeds LV pressure (0 mmHg) → 80 mmHg driving gradient → most left coronary flow occurs in diastole

• RV systolic pressure is only ~25 mmHg → aorta-to-RV gradient remains positive even in systole (95 mmHg)
• Flow occurs in both systole and diastole, with only partial reduction in systole

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Factors Altering Coronary Blood Flow

1. Local Metabolic Factors (Primary / Dominant Mechanism)

• When myocardial work increases → increased O2 consumption → local hypoxia → arteriolar vasodilation → increased coronary flow (active hyperemia)
• When coronary occlusion is transiently relieved → surge in flow proportional to the O2 debt accumulated (reactive hyperemia)

• Mechanism: Increased myocardial work → ATP degraded to ADP → AMP → adenosine
• Adenosine diffuses out of myocytes and causes profound arteriolar vasodilation
• Adenosine is the principal mediator of both active and reactive hyperemia in the coronary circulation
• Basis for pharmacological coronary stress testing (adenosine/dipyridamole)

• CO2 accumulation, H⁺ (lactic acidosis), decreased O2 tension
• Nitric oxide (NO) from endothelium - tonic vasodilation
• Prostacyclin (PGI2) - endothelial vasodilator

2. Aortic Diastolic Pressure (Perfusion Pressure)

• Coronary perfusion pressure (CPP) = Aortic diastolic pressure - Left ventricular end-diastolic pressure (LVEDP)
• Since the LV is perfused in diastole, aortic diastolic BP is the driving pressure
• Conditions that reduce CPP and impair coronary flow:
  • Hypotension (shock, induction of anaesthesia)
  • Aortic regurgitation (low diastolic BP + elevated LVEDP)
  • Elevated LVEDP (heart failure, LV hypertrophy)
  • Tachycardia (reduces diastolic time)

3. Heart Rate

• Tachycardia decreases diastolic filling time → reduces left coronary blood flow
• Simultaneously increases myocardial O2 demand
• This is the most dangerous combination in ischaemic heart disease patients
• Anaesthetic goal: avoid tachycardia in patients with coronary artery disease

4. Intramyocardial / Extravascular Compression

• Ventricular wall tension during systole compresses intramural coronary vessels
• Increased by: high preload (elevated LVEDV), high afterload (hypertension, aortic stenosis), ventricular hypertrophy
• The subendocardium is most vulnerable because wall tension is highest at the inner layer
• Subendocardium is the most common site of myocardial infarction

5. Autonomic Nervous System

• Net result: sympathetic stimulation increases coronary flow via metabolic override
• In susceptible individuals, disproportionate alpha vasoconstriction causes coronary vasospasm (Prinzmetal's angina)

• Direct: acetylcholine causes direct vasodilation of coronary arteries
• Indirect: reduces HR and contractility → decreased O2 demand → reduced metabolic drive → flow decreases
• Net result: mild decrease in coronary flow (indirect effect dominates)

6. Coronary Autoregulation

• Coronary flow is maintained relatively constant over a perfusion pressure range of 60-140 mmHg
• Below 60 mmHg (or above 140 mmHg), autoregulation fails and flow becomes pressure-dependent
• Mechanism: myogenic response (intrinsic smooth muscle) + metabolic feedback
• In severe coronary artery stenosis, vasodilatory reserve is exhausted at rest → any further reduction in perfusion pressure causes ischemia

7. Pharmacological Agents Relevant to Anaesthesia

8. Other Pathological Factors

• Coronary artery stenosis: Limits maximum vasodilatory reserve; resting flow maintained by autoregulation until stenosis >70% diameter; flow reserve exhausted on exertion
• Coronary vasospasm: Exaggerated alpha-adrenergic or endothelin-mediated constriction
• Elevated right atrial/venous pressure: Reduces coronary outflow gradient (as in cardiac tamponade, PEEP, heart failure)
• Aortic stenosis: Increased wall stress + systolic compression + LV hypertrophy → severe subendocardial ischemia risk
• Anaemia: Reduces O2-carrying capacity → compensatory vasodilation to maintain O2 delivery

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Anaesthetic Relevance - Summary Points

1. Maintain heart rate in the 50-70 range in ischaemic heart disease - tachycardia is the enemy
2. Maintain diastolic BP - this is the coronary driving pressure; hypotension during induction is dangerous
3. Avoid increases in LVEDP - rises with volume overload, failure, or myocardial depression
4. Tachycardia + hypotension = most dangerous combination in CAD (reduces CPP and diastolic time simultaneously)
5. Coronary steal (with volatile agents/vasodilators) occurs when flow is diverted away from areas beyond a fixed stenosis
6. Beta-blockers protect by reducing HR, prolonging diastole, and reducing O2 demand

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Cardiac Output: Definition, Determinants and Factors Affecting It

Definition

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

• Normal resting CO: ~5 L/min (range 4-8 L/min) in a 70 kg adult
• Stroke volume: ~70 mL/beat; Heart rate: ~72 beats/min
• Cardiac Index (CI) = CO ÷ Body Surface Area = ~3 L/min/m² (normalises for body size)
• CI is a better clinical comparator than absolute CO

• End-diastolic volume (EDV): Volume in ventricle at end of diastole (~140 mL)
• End-systolic volume (ESV): Volume remaining after ejection (~70 mL)
• Stroke volume = EDV - ESV = 140 - 70 = 70 mL
• Ejection fraction (EF) = SV/EDV = 70/140 = 50-65% (normal >55%)

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Measurement of Cardiac Output

1. Fick Principle

CO = O2 consumption (VO2) / (CaO2 - CvO2)

2. Indicator Dilution Methods

• Dye dilution (indocyanine green): indicator injected into venous system, detected in arterial blood
• Thermodilution (PA catheter - Swan-Ganz): cold saline injected into RA, temperature change detected in pulmonary artery. Most widely used in clinical anaesthesia

3. Echocardiography (Doppler)

• CO = SV × HR, where SV = CSA(LVOT) × VTI(LVOT)
• Widely used intraoperatively with TEE/TTE

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Four Primary Determinants of Cardiac Output

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1. PRELOAD

Frank-Starling Law (Fundamental basis)

• The volume ejected per beat depends on the volume present at end-diastole
• As EDV increases → sarcomere stretch increases → greater overlap of actin-myosin cross-bridges → stronger contraction → higher SV
• This is the length-tension relationship applied to the whole ventricle
• Frank-Starling ensures cardiac output automatically equals venous return in steady state

Factors Increasing Preload (↑ EDV → ↑ CO)

• Increased venous return (exercise, autotransfusion, Trendelenburg position)
• Increased blood volume (IV fluids, pregnancy)
• Increased venomotor tone (sympathetic activation)
• Bradycardia (longer diastolic filling time)
• Mitral/tricuspid regurgitation (volume overload)

Factors Decreasing Preload (↓ EDV → ↓ CO)

• Haemorrhage, dehydration
• Vasodilators (nitrates, spinal/epidural anaesthesia → venodilation)
• Positive pressure ventilation / high PEEP (reduces venous return)
• Cardiac tamponade, tension pneumothorax (compresses cardiac chambers)
• Tachycardia (reduced diastolic filling time)
• Patient positioning (reverse Trendelenburg, sitting position)

Clinical Relevance to Anaesthesia

• Induction of anaesthesia typically reduces preload via venodilation and sympatholysis
• Positive pressure ventilation markedly reduces venous return and preload
• Fluid boluses increase preload - used to treat intraoperative hypotension

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2. AFTERLOAD

• Systemic vascular resistance (SVR) for the LV
• Pulmonary vascular resistance (PVR) for the RV
• More precisely described by ventricular wall stress (LaPlace's law):

Wall Stress (σ) = (Pressure × Radius) / (2 × Wall Thickness)

LaPlace's Law - Key Points

• A dilated ventricle (↑ radius) faces higher wall stress for the same aortic pressure
• A hypertrophied ventricle (↑ wall thickness) has lower wall stress - this is why hypertrophy develops as a compensatory response to chronic pressure overload

Relationship to Stroke Volume

• Increased afterload → increased wall stress → reduced velocity of myocyte shortening → reduced stroke volume and CO
• The ventricle must do more work to generate the same SV against a higher afterload

Factors Increasing Afterload (↓ SV → ↓ CO)

• Hypertension, aortic stenosis
• Vasoconstriction (hypothermia, pain, sympathetic activation)
• Vasopressors (phenylephrine, norepinephrine)
• Ventricular dilation (heart failure - LaPlace's law)

Factors Decreasing Afterload (↑ SV → ↑ CO)

• Vasodilators (volatile agents, SNP, hydralazine)
• Sympathetic blockade (spinal/epidural anaesthesia)
• IABP (intra-aortic balloon pump) - reduces LV afterload by deflating during systole
• ACE inhibitors, calcium channel blockers

Clinical Relevance to Anaesthesia

• Volatile anaesthetics reduce SVR/afterload - beneficial in high-afterload states but can cause hypotension in already vasodilated patients
• Phenylephrine increases afterload - may reduce CO despite raising BP
• In heart failure, excessive afterload reduction must be balanced to avoid hypotension

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3. CONTRACTILITY (Inotropy)

• Contractility shifts the entire Frank-Starling curve up (positive) or down (negative)
• Clinically indexed by ejection fraction, dP/dt max (rate of LV pressure rise), or end-systolic pressure-volume relationship (ESPVR)

Cellular Mechanism

• Beta-1 adrenoceptor activation → ↑ cAMP → ↑ PKA activity → phosphorylation of L-type Ca²⁺ channels → ↑ Ca²⁺ entry → ↑ SR Ca²⁺ release → stronger actin-myosin cross-bridge formation
• Contractility correlates directly with cytosolic Ca²⁺ concentration

Factors Increasing Contractility (Positive Inotropes)

Factors Decreasing Contractility (Negative Inotropes)

LV Pressure-Volume Loop - Effect of Contractility

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4. HEART RATE

CO = SV × HR

Effect of Heart Rate on CO

Bainbridge Reflex

• Stretch of the right atrium (from increased venous return) increases heart rate via a vagal reflex arc through the medulla, ensuring CO keeps pace with venous return

Bowditch / Treppe Effect

• At higher heart rates, increased intracellular Ca²⁺ cycling increases contractility (positive inotropy from tachycardia)

Factors Increasing Heart Rate

• Sympathetic activation, catecholamines, pain, anxiety
• Hypovolaemia (reflex tachycardia)
• Drugs: atropine, ketamine, pancuronium, salbutamol
• Fever, thyrotoxicosis, anaemia

Factors Decreasing Heart Rate

• Vagal stimulation (laryngoscopy, oculocardiac reflex, peritoneal traction)
• Beta-blockers, digoxin, calcium channel blockers (non-dihydropyridine)
• Hypothermia, hypothyroidism
• High spinal anaesthesia (blocks cardiac accelerator fibres T1-T4)
• Increased ICP (Cushing's reflex - bradycardia with hypertension)

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Other Factors Affecting Cardiac Output

5. Venous Return

• In the steady state, CO = venous return; they are equal and interdependent
• The heart cannot pump more than it receives (Frank-Starling)
• Venous return is driven by the mean systemic filling pressure (MSFP) gradient:

Venous Return = (MSFP - Right Atrial Pressure) / Venous Resistance

• Factors increasing venous return: increased blood volume, venoconstriction, skeletal muscle pump, respiratory pump (inspiration), Trendelenburg, exercise
• Factors decreasing venous return: venodilation (nitrates, epidural), positive pressure ventilation, hypovolaemia, tamponade

6. Autonomic Nervous System

7. Metabolic / Physiological States

8. Anaesthetic Agents and Their Effect on CO

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Summary Diagram

CARDIAC OUTPUT = STROKE VOLUME × HEART RATE
                      |
         ┌────────────┼────────────┐
      PRELOAD     AFTERLOAD   CONTRACTILITY
      (EDV)        (SVR/Wall    (Inotropy)
                   Stress)
         ↑              ↑            ↑
   Venous return    Aortic BP    Sympathetic
   Blood volume     SVR          Catecholamines
   Frank-Starling   LaPlace      Ca²⁺ availability

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Key Normal Values (for exam)

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Bainbridge Reflex

Definition

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Receptor (Afferent Limb)

• Receptor type: Low-pressure mechanoreceptors (stretch receptors / volume receptors)
• Location: Right atrial wall and the cavoatrial junction (junction of the venae cavae with the right atrium)
• These are Type B atrial receptors - they fire in response to passive stretch of the atrial wall during filling
• They are distinct from arterial baroreceptors (high-pressure receptors in the carotid sinus and aortic arch)
• Stimulus: Increased right atrial filling pressure and wall stretch - caused by increased venous return / blood volume

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Afferent Pathway

• Stretch receptor signals travel via vagal afferent fibres (CN X) to the nucleus tractus solitarius (NTS) in the medulla
• Signals then reach the cardiovascular centre in the medulla oblongata (cardioinhibitory and cardioacceleratory areas)

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Efferent Pathway and Response

• The cardiovascular centre responds by:
  1. Inhibiting parasympathetic (vagal) outflow to the SA node - reduces vagal tone
  2. Increasing sympathetic outflow to the SA node and myocardium via cardiac sympathetic nerves
• Result: Tachycardia (increased heart rate)
• The effect on contractility and stroke volume is minimal - the primary response is on heart rate alone

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Mechanism of Tachycardia - Two Components

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Physiological Significance

1. Prevents congestion - prevents damming of blood in the veins, right atrium, and pulmonary circulation when venous return increases
2. Matches CO to venous return - increases heart rate and therefore cardiac output to match the increased inflow; works in concert with the Frank-Starling mechanism
3. Counterbalances the arterial baroreceptor reflex - the two reflexes work in opposition:

• During volume loading, the Bainbridge reflex prevails and HR increases
• During volume depletion, the arterial baroreceptor reflex dominates and HR also increases
• Heart rate is at its minimum when circulating volume is normal (both reflexes balanced)

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Important Features

• The magnitude of the heart rate increase is greatest when the baseline heart rate is slow (the reflex saturates at higher baseline rates)
• At fast baseline heart rates, infusion of fluids may paradoxically cause a small decrease in HR (arterial baroreceptors activated by rising BP dominate over the Bainbridge reflex)
• The Bainbridge reflex is not solely dependent on a neural arc - direct mechanical stretch of the SA node also contributes
• Efferent limb involves both sympathetic and parasympathetic pathways (primarily withdrawal of vagal tone + sympathetic activation)

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Additional Atrial Stretch Responses (Clinically Linked)

• ↓ ADH secretion (from hypothalamus) → increased water excretion
• ↓ Renal sympathetic tone → renal vasodilation → natriuresis and diuresis
• ↑ ANP (Atrial Natriuretic Peptide) release → natriuresis, diuresis, vasodilation
• Together these responses reduce blood volume back toward normal

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Anaesthetic Relevance

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Summary (for quick recall)

↑ Venous Return
      ↓
Right atrial stretch
      ↓
Type B low-pressure receptors (cavoatrial junction)
      ↓
Vagal afferents → NTS → Medullary cardiovascular centre
      ↓
↓ Vagal efferent tone  +  ↑ Sympathetic efferent
      ↓                          ↓
SA node: direct stretch     SA node stimulation
      ↓
↑ Heart Rate → ↑ Cardiac Output → prevents atrial congestion

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