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Coronary Circulation and Physiology

Notes for Anaesthesia (Miller's, Barash, Guyton)

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1. Coronary Anatomy

Left Coronary System

• The Left Main Coronary Artery (LMCA) arises from the left aortic sinus and divides into:
  • Left Anterior Descending (LAD): courses down the interventricular groove; gives rise to diagonal branches (anterolateral LV wall) and septal branches (interventricular septum, bundle branches, Purkinje system); terminates at the LV apex
  • Left Circumflex (LCx/LCCA): courses along the left AV groove; gives rise to obtuse marginal branches supplying the lateral LV wall

Right Coronary System

• Right Coronary Artery (RCA): traverses the right AV groove; gives off acute marginal branches to the RV anterior wall
• In 85% (right-dominant): RCA gives rise to the Posterior Descending Artery (PDA) supplying the posterior-inferior LV
• In 15% (left-dominant): LCx gives rise to the PDA

Territory Summary (Barash, p. 850-851)

Clinical pearl: Ischemia of the dominant artery territory can cause SA/AV nodal dysfunction and bradyarrhythmias. RCA or LAD occlusion can both cause RV dysfunction.

Papillary Muscle Blood Supply

• Posterior-medial papillary muscle: single supply from RCA or LCx (2:1 ratio) - highly vulnerable to ischemia; ~1/3 of people have dual supply (less susceptible)
• Anterolateral papillary muscle: dual supply from LAD + LCx - ischemia unusual

Coronary Venous Drainage

• ~75% of LV coronary venous blood returns via the coronary sinus to the right atrium
• RV venous blood returns via anterior cardiac veins directly to RA
• Small amount via Thebesian veins into all cardiac chambers (physiological right-to-left shunt)

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2. Coronary Physiology

2.1 Basic Flow Dynamics - Poiseuille's Law

Flow = Perfusion Pressure / Vascular Resistance

• Resistance varies with the 4th power of vessel radius - even tiny changes in caliber produce large changes in resistance
• Coronary blood flow is exquisitely sensitive to arteriolar vasomotor tone
• Blood viscosity (driven mainly by hemoglobin concentration) is a minor factor unless extreme polycythemia or haemodilution is present

• ~225-250 mL/min (~70 mL/min/100 g)
• Represents 4-5% of cardiac output
• With strenuous exercise: increases 3-4 fold (but cardiac workload increases 6-9 fold, so efficiency of oxygen utilisation must increase)

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2.2 Coronary Perfusion Pressure (CPP)

• Coronary venous pressure is negligible
• Elevated LVEDP impedes subendocardial blood flow - critical in aortic stenosis, LVH, heart failure
• After coronary stenosis, distal vessels dilate maximally - flow becomes pressure-dependent and manipulating CPP is the primary tool for managing ischaemia

CPP (LV) = Aortic DBP - LVEDP

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2.3 Phasic Nature of Coronary Flow - Systole vs Diastole

• ~70-80% occurs during diastole because extravascular compressive forces during systole markedly impede subendocardial intramural vessel flow
• During systole: intraventricular pressure and coronary vascular resistance both rise, compressing intramural vessels
• During diastole: metabolically mediated arteriolar dilation preferentially increases subendocardial flow

• Normal subepicardial : subendocardial flow = 1:1 (preserved by metabolic dilation during diastole)
• This ratio is compromised first by tachycardia, stenosis, or hypertrophy

• Intracavitary pressures remain below aortic pressure throughout the cardiac cycle
• Therefore, compressive forces do NOT significantly impede flow - RV/LA/RA flow is relatively continuous throughout the cardiac cycle

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2.4 Heart Rate and Coronary Flow

• Tachycardia shortens diastole disproportionately more than systole (non-linear relationship)
• Subendocardial flow is initially maintained by recruiting coronary flow reserve
• When flow reserve is exhausted (stenosis, LVH), tachycardia causes subendocardial ischaemia
• This is the mechanism behind beta-blockers as anti-ischaemic drugs - by slowing HR, they lengthen diastole and restore subendocardial perfusion time

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2.5 Myocardial Metabolism and Oxygen Requirements

• Heart weight = 0.5% of total body weight, yet accounts for 7% of total body oxygen consumption
• ~75% of haemoglobin-bound oxygen is extracted across the myocardial capillaries
• Coronary sinus PO₂ ≈ 20 mmHg (extremely low - near-maximal extraction at rest)

1. Fatty acids (predominant substrate, ~60-70%)
2. Glucose
3. Lactate (taken up and oxidised under normal conditions; produced and released during ischaemia)

• Anaerobic glycolysis is activated but ATP yield is severely limited
• Contraction ceases within 10-15 seconds of acute coronary occlusion (unless collateral flow is present)
• Lactate is released (rather than consumed) - lactate production is a marker of myocardial ischaemia

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3. Regulation of Coronary Blood Flow

3.1 Metabolic (Local) Regulation - DOMINANT MECHANISM

• Most important regulator of coronary flow
• Coronary flow is tightly coupled to myocardial oxygen demand ("flow-metabolism coupling")
• When O₂ demand rises, the myocardium releases vasodilator mediators that dilate coronary arterioles
• Key mediators of metabolic vasodilation:
  • Adenosine (most important) - produced from AMP breakdown during increased ATP turnover; potent arteriolar dilator
  • Nitric oxide (NO) - produced by endothelial NOS; causes SMC relaxation
  • Hypoxia - direct relaxation of vascular smooth muscle
  • CO₂ / H⁺ (local acidosis) - vasodilation
  • K⁺ released during repolarisation
  • Prostaglandins (prostacyclin, PGI₂)

3.2 Autoregulation

• Coronary flow is maintained constant over a CPP range of approximately 60-140 mmHg
• Below this range (CPP < 60 mmHg): flow falls (pressure-dependent zone) → ischaemia
• Above this range (CPP > 140 mmHg): flow rises (pressure breakthrough)
• Autoregulation is mediated by myogenic response of arteriolar smooth muscle + metabolic feedback
• In stenotic vessels: distal vessels are already maximally dilated to maintain resting flow; autoregulation is abolished and flow becomes entirely pressure-dependent - hence the importance of CPP in CAD patients
• Autoregulation is impaired by: volatile anaesthetics (dose-dependent), extreme tachycardia, severe hypoxia, marked acidosis

3.3 Neural (Autonomic) Regulation

• The coronary vasculature receives both sympathetic and parasympathetic innervation
• Sympathetic (α₁-adrenergic): direct vasoconstriction of coronary vessels
• Sympathetic (β₂-adrenergic): vasodilation (less prominent)
• Net effect of sympathetic stimulation: vasodilation predominates because metabolic effects (increased HR, contractility → increased O₂ demand → metabolic vasodilation) override the direct α₁ constrictive effect
• Parasympathetic (vagal): mild coronary vasodilation; acetylcholine acts via endothelial muscarinic receptors to produce NO
• Coronary conductance is regulated by arterial baroreflex: vasodilator response is induced by a rise in aortic pressure
• At low plasma fentanyl concentrations (1-2 ng/mL), baroreflex coronary control is enhanced; at higher concentrations, it is depressed (Miller's, p. 2769)

3.4 Endothelial Regulation

• Nitric oxide (NO) - synthesised by eNOS; released in response to shear stress, acetylcholine, bradykinin, substance P
• Prostacyclin (PGI₂) - via endothelial COX pathway
• Endothelium-derived hyperpolarising factor (EDHF)

• Endothelin-1 (ET-1) - potent vasoconstrictor; upregulated in atherosclerosis, heart failure
• Thromboxane A₂ (TXA₂)

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4. Determinants of Myocardial Oxygen Supply and Demand

4.1 Oxygen Supply Determinants

4.2 Oxygen Demand Determinants

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

• LV dilatation (increased radius) → increased wall stress → increased O₂ demand
• LV hypertrophy (increased wall thickness) → reduced wall stress per unit - but capillary density may not increase proportionately, reducing O₂ supply to the hypertrophied myocardium

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5. Coronary Flow Reserve (CFR)

• CFR = Maximum coronary blood flow (after maximal vasodilation) / Resting coronary blood flow
• Normal CFR ≈ 4-5 (flow can increase 4-5 fold from baseline)
• CFR is the physiological "buffer" that allows increased demand (exercise, tachycardia) to be met
• A stenosis of >50% diameter begins to limit maximum flow; >70-80% impairs resting flow

• Coronary artery stenosis (most common)
• LV hypertrophy (increased resting flow + reduced maximum flow due to reduced capillary density)
• Microvascular disease (diabetes, hypertension)
• Tachycardia (exhausts reserve)
• Anaemia, hypotension

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6. Coronary Steal Phenomenon

• Occurs when a vasodilator (e.g., adenosine, dipyridamole, isoflurane) dilates normal vessels but cannot further dilate vessels distal to a stenosis (already maximally dilated)
• Blood is "stolen" from the ischaemic territory through collateral vessels to the dilated normal territory
• Isoflurane: most implicated volatile agent; causes coronary vasodilation and can produce steal in patients with "steal-prone" anatomy (parallel coronary stenoses with collaterals)
• Opioids: do NOT produce steal phenomena and do not diminish coronary vasomotor response (Miller's, p. 2769)
• Steal-prone anatomy: requires two stenoses and a collateral vessel connecting the territories; relatively uncommon (~23% of patients with CAD have steal-prone anatomy)

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7. Anaesthetic Effects on Coronary Circulation

Volatile Anaesthetics

• All volatile agents decrease MVO₂ by reducing HR, contractility, and wall tension (decrease in SVR reduces afterload)
• Isoflurane, desflurane, sevoflurane: all produce coronary vasodilation via K-ATP channel opening
• Ischaemic preconditioning by volatile agents: clinically significant myoprotective mechanism mediated through K-ATP channel opening, adenosine receptors, and PKC activation

Opioids (Miller's, p. 2769)

• No significant effect on coronary vasomotion or myocardial metabolism at clinical doses
• Do NOT produce steal phenomena
• Do not diminish large coronary arteriole response to vasoactive agents
• Baroreflex coronary control: enhanced at low fentanyl concentrations (1-2 ng/mL), depressed at high concentrations
• Opioids can mimic ischaemic preconditioning - opioid receptor stimulation (especially κ and δ receptors) reduces infarct size in animal models
• Remote preconditioning (ischaemia of intestine, kidney, limb) is mediated through myocardial κ-opioid receptors
• Postconditioning: δ-opioid receptor activation during early reperfusion protects against infarction; can be enhanced by morphine + isoflurane combination
• Late preconditioning (24 hours after morphine) has also been demonstrated in animal models

Perioperative Ischaemia Management

• Vigilant monitoring needed for supply-demand imbalance: ECG with ST-segment analysis + TEE for regional wall motion abnormalities
• Causes of reduced supply: hypotension, tachycardia, anaemia, coronary vasoconstriction
• Causes of increased demand: tachycardia, increased afterload (hypertension), increased contractility
• Beta-blockers: cornerstone - reduce HR (lengthen diastole, reduce demand), and prevent even small perioperative HR increases

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8. Myocardial Ischaemia and Infarction

Ischaemia Cascade (in order of appearance):

1. Metabolic changes (lactate production, reduced ATP)
2. Diastolic dysfunction (relaxation impaired)
3. Systolic dysfunction (regional wall motion abnormality - detected by TEE)
4. ECG changes (ST changes)
5. Symptoms (chest pain) - last to appear

Consequences of Acute Myocardial Infarction (Guyton, p. 271-272):

1. Decreased cardiac output - systolic stretch: ischaemic muscle passively bulges outward during systole, wasting contractile energy; cardiogenic shock if >40% LV infarcted (mortality 40-50%)
2. Pulmonary oedema - reduced CO → reduced renal flow → fluid retention → elevated pulmonary venous pressure
3. Ventricular fibrillation - most common cause of sudden death; two high-risk windows: within 10 minutes of infarction, and 1-several hours later

Ischaemic Preconditioning

• Brief episodes of ischaemia-reperfusion make the myocardium more resistant to subsequent prolonged ischaemia
• Mediated by: adenosine A₁ receptors, K-ATP channels, PKC, mitochondrial permeability transition pore
• Early preconditioning: within minutes, lasts 1-2 hours
• Late preconditioning: 24-72 hours after stimulus (mediated by protein synthesis, iNOS)
• Opioids and volatile anaesthetics can both pharmacologically precondition the heart

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9. Quick Reference - Key Numbers

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• Barash, Cullen & Stoelting's Clinical Anesthesia, 9e - Chapter 12 (Coronary Anatomy, pp. 850-858; Coronary Physiology, pp. 857-869)
• Miller's Anesthesia, 10e - Coronary Anatomy & Determinants of MVO₂ (pp. 7584-7586); Opioids & Coronary Circulation (pp. 2769-2770)
• Guyton & Hall Textbook of Medical Physiology - Coronary Circulation (pp. 270-272)