What effect does acetylcholine have on coronary vessels?

Effect of Acetylcholine on Coronary Vessels

In coronary arteries with normal endothelium, intracoronary acetylcholine dilates epicardial and microvascular circulation, increasing coronary blood flow. However, when the endothelium is damaged or disrupted, intracoronary acetylcholine induces vasoconstriction and a decrease in coronary blood flow. 1

Physiological Mechanism

The response of coronary vessels to acetylcholine depends on the functional status of the endothelium:

Normal Endothelium Response

• Acetylcholine binds to muscarinic receptors on endothelial cells
• Stimulates release of endothelium-derived relaxing factor (nitric oxide)
• Results in vasodilation of both epicardial and microvascular coronary circulation
• Increases coronary blood flow

Damaged Endothelium Response

• With endothelial dysfunction or damage, acetylcholine acts directly on vascular smooth muscle
• Causes paradoxical vasoconstriction through direct muscarinic receptor stimulation
• Decreases coronary blood flow
• May precipitate coronary vasospasm

Clinical Applications

Acetylcholine testing is used in the cardiac catheterization laboratory to:

1. Assess endothelial function
2. Diagnose coronary vasospasm
3. Evaluate patients with angina and non-obstructive coronary arteries (ANOCA/INOCA)

Standardized Testing Protocol

• Acetylcholine is administered in graded doses:
  • Low dose (2-20 μg) to assess endothelial-dependent vasodilation
  • High dose (100-200 μg) to assess endothelial dysfunction and vasoconstriction
• Continuous monitoring with:
  • Doppler flow measurements
  • 12-lead ECG
  • Symptom assessment
  • Coronary angiography after each dose 1

Diagnostic Criteria

• Macrovascular spasm: Symptoms + ischemic ECG changes + ≥90% reduction in coronary lumen
• Microvascular spasm: Symptoms + ischemic ECG changes + <90% reduction in coronary lumen 1

Risk Factors Affecting Response

The acetylcholine response correlates with coronary risk factors:

• Elevated serum cholesterol
• Male gender
• Family history of coronary disease
• Advanced age
• Total number of risk factors 2

Clinical Significance

1. Early marker of atherosclerosis: Paradoxical vasoconstriction to acetylcholine occurs early in coronary atherosclerosis, even before angiographically visible disease 3

2. Prognostic value: Endothelial dysfunction identified by abnormal acetylcholine response is associated with poor cardiovascular outcomes 1

3. Diagnostic tool: Helps identify the cause of chest pain in patients with non-obstructive coronary arteries, distinguishing between:

   • Epicardial coronary vasospasm
   • Microvascular dysfunction
   • Non-cardiac chest pain 1

Safety Considerations

• Acetylcholine testing should only be performed in specialized laboratories by highly experienced personnel
• Bradycardia may occur due to cholinergic effects on the atrioventricular node
• The vasospastic effect is rapidly transient and can be reversed with intracoronary nitroglycerin
• Testing should be avoided in patients with significant left main disease, advanced 3-vessel disease, high-grade obstructive lesions, significant valvular stenosis, or advanced heart failure 1

Correlation with Peripheral Endothelial Function

There is a strong correlation between coronary and brachial artery endothelial function in response to acetylcholine, suggesting that peripheral vascular testing may serve as a surrogate for coronary endothelial function 4, 5.