The angiotensin converting enzyme inhibitor perindopril improves survival after experimental myocardial infarction in pigs.
In this randomized, blinded study the effect of the angiotensin converting enzyme inhibitor perindopril on electrical stability after myocardial infarction in pigs was compared to placebo. The left anterior descending artery was occluded for 45 min. Perindoprilat (0.06 mg/kg, n = 12) or saline (n = 12) was injected 15 min before reperfusion. Treatment was continued till day 13 with perindopril (12 mg, once daily) or placebo. At day 14 an electrophysiologic study was performed. The release of creatine phosphokinase did not differ significantly. During the subsequent days, seven of 12 placebo-treated pigs died (six within 24 h), whereas two of the 12 perindopril-treated pigs died (one within 24 h; p less than 0.04). Sustained ventricular tachycardia was inducible in one of five placebo-treated pigs versus three of 10 perindopril-treated survivors (NS). Late potentials had developed in one placebo-treated pig but not in pigs that received perindopril. Characteristics of infarct border zone heterogeneity (percentages of a reference electrode in viable myocardium) such as a dispersion of current thresholds (127 +/- 96 vs. 238 +/- 463% in perindopril-treated pigs, NS) and refractoriness (9.8 +/- 8.4 vs. 11.9 +/- 6.0% in perindopril-treated pigs, NS) were comparable. This treatment with perindopril significantly improved survival while electrical stability was comparable between survivors. The latter indicates that a comparable electrical stability 2 weeks after myocardial infarction is obtained in perindopril-treated pigs at a significantly higher survival rate.
Tobé
T J
TJ
Department of Pharmacology/Clinical Pharmacology, University of Groningen, The Netherlands.
de Langen
C D
CD
Weersink
E G
EG
van Wijngaarden
J
J
Bel
K J
KJ
de Graeff
P A
PA
van Gilst
W H
WH
Wesseling
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004311:Double-Blind Method; D004558:Electric Stimulation; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D020913:Perindopril; D011897:Random Allocation; D013552:Swine; D013610:Tachycardia / Q000188:drug therapy
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril