Pretreatment with intracoronary enalaprilat protects human myocardium during percutaneous coronary angioplasty.
OBJECTIVE
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.
Leesar
Massoud A
MA
Division of Cardiology, University of Louisville, Louisville, Kentucky.
Jneid
Hani
H
Division of Cardiology, University of Louisville, Louisville, Kentucky.
Tang
Xian-Liang
XL
Division of Cardiology, University of Louisville, Louisville, Kentucky.
Bolli
Roberto
R
Division of Cardiology, University of Louisville, Louisville, Kentucky.. Electronic address: rbolli@louisville.edu.
D000787:Angina Pectoris / Q000175:diagnosis* / Q000188:drug therapy* / Q000628:therapy; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D016009:Chi-Square Distribution; D002908:Chronic Disease; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D004562:Electrocardiography; D015773:Enalaprilat / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D036502:Infusions, Intralesional; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D008875:Middle Aged; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014654:Vascular Patency / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D015773:Enalaprilat