Pretreatment with angiotensin-converting enzyme inhibitors attenuates ischemia-reperfusion injury

Background. The Heart Outcomes Prevention Evaluation (HOPE) trial demonstrated that ischemic events are decreased in patients receiving angiotensin-converting enzyme (ACE) inhibitors. This study sought to determine whether pretreatment with ACE inhibitors would attentuate ischemic injury during surgical revascularization of ischemic myocardium. Methods. In a porcine model, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest, and 180 minutes of reperfusion. Ten pigs received quinapril (20 mg PO q.d.) for 7 days prior to surgery; 10 others received no-ACE inhibitors. Results. Quinapril-treated animals required less cardioversions for ventricular arrhythmias (1.58 ± 0.40 vs 2.77 ± 0.22; p < 0.05), had higher wall motion scores assessed by two-dimensional echocardiography (4 = normal to −1 = dyskinesia; 2.11 ± 0.10 vs 1.50 ± 0.07; p < 0.05), more complete coronary artery endothelial relaxation to bradykinin (45% ± 3% vs 7% ± 4%; p < 0.005), and lower infarct size (24.0% ± 3.0% vs 40.0% ± 1.7%; p < 0.0001). Conclusions. ACE inhibition prior to coronary revascularization enhances myocardial protection by decreasing ventricular irritability, improving regional wall motion, lowering infarct size, and preserving endothelial function.