What effect does acetylcholine administration have on normal coronary arteries?

Effect of Acetylcholine on Normal Coronary Arteries

In normal coronary arteries with healthy endothelium, acetylcholine causes vasodilation of both epicardial and microvascular coronary circulation, increasing coronary blood flow. 1

Physiological Mechanism

Acetylcholine acts through the following pathway in normal coronary arteries:

• Binds to muscarinic receptors on endothelial cells
• Stimulates the release of endothelium-derived relaxing factor (nitric oxide)
• Results in vasodilation of both epicardial and resistance vessels
• Increases coronary blood flow

This response is considered the normal physiological reaction and indicates healthy endothelial function 1.

Diagnostic Applications

Acetylcholine testing is used in cardiac catheterization laboratories to:

1. Assess endothelial function:

   • Low-dose acetylcholine (2-20 μg) is used to evaluate endothelium-dependent vasodilation
   • In normal arteries, this produces measurable dilation 2, 1

2. Diagnose coronary vasospasm:

   • Higher doses (100-200 μg) may be used to provoke vasospasm in susceptible individuals
   • The test is performed with continuous monitoring of:
     • Doppler flow measurements
     • 12-lead ECG
     • Patient symptoms
     • Coronary angiography after each dose 2

Abnormal Responses

It's important to note that the response to acetylcholine differs in diseased vessels:

• In atherosclerotic arteries: Acetylcholine paradoxically causes vasoconstriction rather than dilation 3
• In early atherosclerosis: Abnormal vasoconstrictor response may occur even before angiographically visible disease 3, 4
• With coronary risk factors: Impaired vasodilatory response correlates with:
  • Hypercholesterolemia
  • Hypertension
  • Male gender
  • Family history of coronary disease
  • Advanced age
  • Total number of risk factors 4, 5

Clinical Protocol

According to the European Society of Cardiology guidelines, a standardized protocol for acetylcholine testing includes:

1. Washout of calcium channel blockers and nitrates for at least 24 hours
2. Sequential administration of acetylcholine:
   • 2 μg intracoronary over 60 seconds
   • 20 μg intracoronary over 60 seconds
   • 100 μg intracoronary over 60 seconds
   • 200 μg intracoronary over 60 seconds (if needed)
3. Followed by nitroglycerin 200 μg intracoronary to reverse any vasospasm
4. Then adenosine administration to assess endothelium-independent vasodilation 2

Safety Considerations

• The vasospastic effect of acetylcholine is rapidly transient
• Any induced vasospasm can be quickly reversed with intracoronary nitroglycerin
• Bradycardia may occur due to cholinergic effects on the atrioventricular node, especially when infused into the right coronary artery 2
• Testing should be performed by experienced interventional cardiologists 1

The response to acetylcholine in coronary arteries serves as an important marker of endothelial health and can help identify early vascular dysfunction even before structural changes become apparent on angiography.