Objectives: We tested the hypothesis that enalaprilat induces preconditioning (PC)-mimetic actions in patients with stable coronary artery disease.
Background: Angiotensin-converting enzyme (ACE) inhibitors increase the bioavailability of bradykinin, which induces cardiac PC.
Methods: Twenty-two patients undergoing coronary angioplasty were randomized to an intracoronary infusion of enalaprilat or placebo, followed 10 min later by a PC protocol.
Results: In control patients, the ST-segment shift was greater during the first inflation than during the second and third inflations, both on the intracoronary electrocardiogram (ECG) (21.0 +/- 2.8 mm vs. 13.0 +/- 2.0 mm and 13.0 +/- 2.0 mm, p < 0.05) and the surface ECG (16.0 +/- 4.0 mm vs. 10.0 +/- 2.0 mm and 9.0 +/- 2.0 mm, p < 0.05). In contrast, enalaprilat-pretreated patients showed no change in ST-segment shift during inflations on either the intracoronary or the surface ECG. During the first inflation, the ST-segment shift was significantly smaller in treated versus control patients. The chest pain score during the first inflation was also significantly smaller in treated patients versus control patients (33.0 +/- 6.0 mm vs. 64.0 +/- 6.0 mm) and did not change in treated patients during the second and third inflations, whereas it decreased significantly in control patients. In a subset of 6 patients, enalaprilat increased coronary blood flow during infusion, but this effect dissipated before the beginning of angioplasty.
Conclusions: Pretreatment with enalaprilat attenuates the manifestations of myocardial ischemia during angioplasty. This is the first in vivo evidence showing that an ACE inhibitor protects human myocardium, possibly via PC-mimetics actions, a novel property that might explain the cardioprotective actions of these drugs.