What is coronary circulation?

Coronary Circulation: Comprehensive Overview

Anatomical Structure

The coronary circulation consists of three major epicardial arteries—the left anterior descending (LAD), circumflex, and right coronary artery (RCA)—that supply oxygenated blood to the myocardium. 1

• The left main coronary artery bifurcates into the LAD and circumflex branches, with the left main ostium including the first 3 mm of the artery 1
• The RCA primarily supplies the right atrium, right ventricle, sinoatrial node, posterior portion of the interventricular septum, and in right-dominant circulation, the inferior wall of the left ventricle 1
• These epicardial vessels branch into progressively smaller arterioles and eventually into the coronary microvasculature, which is responsible for providing oxygen and nutrients directly to myocardial tissue 2

Unique Physiological Characteristics

Diastolic Perfusion Dominance

Myocardial perfusion occurs almost exclusively during diastole, making diastolic blood pressure the primary determinant of coronary perfusion pressure. 3

• During systole, extravascular compressive forces from ventricular contraction significantly impede coronary blood flow, particularly in the subendocardium 4
• This diastolic dependence makes the heart uniquely vulnerable to conditions that reduce diastolic time (tachycardia) or diastolic pressure (hypotension) 5

Coronary Autoregulation

The coronary circulation maintains relatively constant blood flow across a range of perfusion pressures through autoregulation, accomplished by coronary vasodilation in response to falling perfusion pressure. 3

• In conscious instrumented dogs, contractile function remains well maintained at mean coronary filling pressures down to 40 mmHg, corresponding to a diastolic blood pressure of 30 mmHg 3
• The lower limit of autoregulation in dogs with left ventricular hypertrophy is shifted upward by 15 to 20 mmHg but can be partially restored by ACE inhibition with accompanying regression of LV hypertrophy 3
• Critical limitation: This autoregulatory capacity is finite—at the point of maximal vasodilation, further falls in coronary perfusion pressure result in decreased flow 3
• Significant coronary artery disease shifts the lower autoregulatory limit upward, making patients more vulnerable to hypotension 3

Coronary Flow Reserve

Coronary blood flow can increase from resting level to maximum level in response to exercise and other stimuli, with this increase termed coronary flow reserve. 1

• Coronary flow reserve is defined as the difference between resting flow and flow through a maximally dilated coronary circulation at any level of perfusion pressure 3
• Patients with left ventricular hypertrophy or coronary atherosclerosis have reduced coronary flow reserve due to diminished functional or structural capacity of coronary resistance vessels to dilate 3
• Collateral flow sufficient to prevent myocardial ischemia during coronary occlusion amounts to approximately one-fifth to one-fourth (20-25%) of normal flow through the open vessel 6, 7

Metabolic Regulation and Oxygen Balance

Coronary blood flow is tightly coupled to myocardial oxygen consumption to maintain a consistently high level of myocardial oxygen extraction. 8, 4

• The heart is an aerobic organ that can develop only a small oxygen debt, with oxygen extraction nearly maximal even at rest and able to increase little with increased demand 3
• Myocardial ischemia results from an imbalance between myocardial oxygen supply and demand 1, 5
• This tight coupling depends on multiple regulatory pathways including periarteriolar oxygen tension, signals released from cardiomyocytes (adenosine acting on K+(ATP) channels), endothelial factors (prostanoids, nitric oxide, endothelin), and autonomic influences 8, 4

Mechanisms of Flow Regulation During Exercise

• Beta-adrenergic feed-forward control contributes to exercise-induced coronary vasodilation, aided by parasympathetic withdrawal 8
• Withdrawal of endothelin-mediated vasoconstrictor influence also contributes to exercise-induced coronary vasodilation 8
• Coronary blood flow regulation by endothelial and metabolic vasodilator pathways contributes to resting vasomotor tone but does not appear to contribute significantly to exercise-induced coronary vasodilation 8

Coronary Collateral Circulation

Coronary collaterals are an alternative source of blood supply to myocardium jeopardized by ischemia, and well-developed collateral arteries in patients with coronary artery disease mitigate myocardial infarcts and improve survival. 6, 7

• Among individuals without coronary artery disease, preformed collateral arteries preventing myocardial ischemia during brief vascular occlusion are present in 20-25% 6, 7
• In patients with coronary artery disease, collateral arteries preventing myocardial ischemia during brief occlusion are present in approximately one-third of individuals 6, 7
• Determinants of preformed anastomoses include low heart rate and absence of systemic arterial hypertension 7
• The human coronary collateral circulation is very well developed compared with other species 7

Coronary Microvascular Function

A healthy microvasculature with intact and properly functioning endothelium accomplishes oxygen delivery through seamless changes in vascular tone to match supply and demand. 2

• Perturbations in normal microvascular physiology, including endothelial and/or vascular smooth muscle dysfunction, result in impaired function (vasoconstriction, antithrombotic abnormalities) and structural changes (hypertrophic, fibrotic) that lead to microvascular ischemia 2
• Coronary microvascular dysfunction is the primary pathologic driving force in ischemia with non-obstructive coronary artery disease (INOCA), angina with no obstructive coronary arteries (ANOCA), and myocardial infarction with non-obstructed coronary arteries (MINOCA) 2
• Regardless of whether coronary microvascular dysfunction is primary or secondary, it is associated with important increases in morbidity and mortality 2

Pathophysiological Considerations

Atherosclerotic Disease Impact

Atherosclerotic narrowings produce epicardial vessel resistance and can abolish coronary reserve and autoregulation, reducing resting coronary blood flow. 1

• The physiological significance of coronary stenosis, especially for intermediately severe luminal narrowing, cannot be accurately determined by angiography alone 1
• Pressure and flow measurements provide complementary information to anatomic characterization of coronary disease and facilitate timely and objective decision-making about therapy 1

Demand Ischemia Mechanisms

Demand ischemia develops through conditions that create an imbalance between oxygen supply and demand, even without acute coronary plaque rupture. 5

• Coronary blood flow may be compromised by low cardiac output or reduced diastolic blood pressure 5
• Elevated ventricular filling pressures worsen the situation by reducing the driving gradient for coronary perfusion 5
• Oxygen demand simultaneously increases due to elevated ventricular wall stress and neurohormone-mediated increases in heart rate and contractility 5

Common Precipitants of Supply-Demand Mismatch

• Tachycardia/tachyarrhythmias increase myocardial workload while reducing diastolic filling time and increasing oxygen demand 5
• Hypertension elevates left ventricular afterload and myocardial work 5
• Hypotension reduces coronary perfusion pressure 5
• Hypoxemia decreases arterial oxygen content 5
• Anemia reduces oxygen-carrying capacity 5
• Coronary vasospasm transiently reduces coronary blood flow 5

Assessment of Coronary Circulation

Non-Invasive Assessment

Blood flow velocity in the LAD can be assessed non-invasively by transthoracic Doppler echocardiography, with outcome variables including mean coronary blood flow velocity, peak diastolic velocity, mean diastolic velocity, peak systolic velocity, and mean systolic velocity. 3

• Intravenous adenosine infusion of 140 μg/kg/min for 90 seconds allows coronary blood flow reserve quantification and assessment of microvascular function 3
• Critical pitfall: Caution should be exercised about repetitive measurements with short intervals because adenosine itself exerts cardioprotective effects, so measurements on separate days are advisable 3

Invasive Assessment

• Endothelium-dependent vasodilator function is assessed during incremental intra-coronary acetylcholine doses at 1,3,10, and 30 μg/min for 2 minutes at each dose 3
• Non-endothelium-dependent vasodilator function is measured using intracoronary nitroglycerin 0.40 mg 3
• Coronary luminal diameter is assessed by quantitative coronary angiography and coronary blood flow velocity measured by Doppler 3
• Coronary blood flow reserve can be determined using intracoronary adenosine 40 and 80 μg in the right and left coronary artery, respectively 3

Clinical Implications for Morbidity and Mortality

Myocardial infarct size, the most important prognostic determinant after such an event, is the product of coronary artery occlusion time, area at risk for infarction, and the inverse of collateral supply. 6, 7

• Well-developed coronary collateral arteries in patients with coronary artery disease mitigate myocardial infarcts and improve survival 6, 7
• Approximately one-fifth of patients with coronary artery disease cannot be revascularized by percutaneous coronary intervention or coronary artery bypass grafting, making therapeutic promotion of collateral growth a valuable treatment strategy 7
• Potential arteriogenic approaches include treatment with granulocyte colony-stimulating factor, physical exercise training, and external counterpulsation 7