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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

Pretreatment With Intracoronary Enalaprilat Protects Human Myocardium During Percutaneous Coronary Angioplasty

Division of Cardiology, University of Louisville, Louisville, Kentucky.

Manuscript received November 3, 2006; revised manuscript received December 12, 2006, accepted January 1, 2007.

^_* Reprint requests and correspondence: Dr. Roberto Bolli, Division of Cardiology, University of Louisville, Louisville, Kentucky 40292. (Email: rbolli{at}louisville.edu).

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.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   CBF = coronary blood flow   ECG = electrocardiogram   PC = preconditioning   PTCA = percutaneous transluminal coronary angioplasty

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