High tissue affinity angiotensin-converting enzyme inhibitors improve endothelial function and reduce infarct size

Area of Science:

• Cardiovascular Research
• Pharmacology
• Ischemia-Reperfusion Injury

Background:

• Angiotensin-converting enzyme (ACE) inhibitors vary in their tissue ACE inhibition.
• Understanding these differences is crucial for optimizing therapeutic effects during ischemic events.

Purpose of the Study:

• To investigate if ACE inhibitors with high tissue affinity improve endothelial function.
• To determine if this leads to reduced tissue necrosis during ischemia and reperfusion.

Main Methods:

• A porcine model was used, occluding diagonal coronary vessels for 90 minutes.
• Animals received either enalaprilat (low tissue affinity), quinaprilat (high tissue affinity), or no ACE inhibitor.
• Cardioplegic arrest and reperfusion followed occlusion, with subsequent assessment of cardiac function and infarct size.

Main Results:

• ACE inhibitors significantly improved wall motion scores compared to no treatment (p < 0.0001).
• Quinaprilat (high affinity) best preserved endothelial-dependent relaxation to bradykinin (65.8% vs. 32.1% enalaprilat vs. 30.6% no ACE; p < 0.005).
• Quinaprilat treatment resulted in a significantly smaller infarct size (14.3% vs. 24.3% enalaprilat vs. 40.0% no ACE; p < 0.005).

Conclusions:

• Higher affinity of ACE inhibitors to tissue ACE correlates with better endothelial function preservation.
• High-affinity ACE inhibitors significantly reduce myocardial necrosis during coronary revascularization.