Antiarrhythmic effects of the angiotensin converting enzyme inhibitor perindoprilat in a pig model of acute regional myocardial ischemia.
Previous studies on the possible antiarrhythmic effects of angiotensin converting enzyme (ACE) inhibitors during early ischemia in pigs have been inconclusive or negative; however, proof of adequate ACE inhibition was not provided. Perindoprilat, 0.06 mg/kg, i.v., was administered 30 min prior to ligation of the anterior descending coronary artery (CAL) in anesthetised open-chest pigs. Plasma ACE activity was decreased by 95.0 +/- 1.9% when measured 5 min before CAL. Within 5 min of CAL, the ventricular fibrillation threshold (VFT) in the control group was decreased from 11.8 +/- 1.9 to 7.2 +/- 1.2 mA (p less than 0.01). Perindoprilat prevented the fall in the VFT and the increase in left ventricular end-diastolic pressure caused by CAL. Perindoprilat decreased arterial pressure. Cardiac output (thermodilution) was decreased by 23 +/- 3% after CAL in the control group and by only 10 +/- 5% (p less than 0.05) in the perindoprilat group (both versus pre-CAL values). In the control group cyclic AMP was increased from 0.97 +/- 0.04 (pre-CAL) to 1.16 +/- 0.04 nmol/g (p less than 0.05) in the central ischemic zone 20 min after CAL. Perindoprilat prevented this increase in cyclic AMP. Twenty minutes after CAL blood flow (microsphere method) in the nonischemic zone of the perindoprilat group was increased, whereas blood flow in the central ischemic zone was decreased compared to the control group. However, levels of tissue metabolites (ATP, phosphocreatine, lactate) measured in drill biopsies in the same zones of the two groups were similar.(ABSTRACT TRUNCATED AT 250 WORDS)
Muller
C A
CA
MRC Ischaemic Heart Disease Research Unit, Groote Schuur Hospital, Cape Town, South Africa.
Opie
L H
LH
Peisach
M
M
Pineda
C A
CA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D010725:Phosphocreatine / Q000378:metabolism; D013552:Swine; D014693:Ventricular Fibrillation
D000806:Angiotensin-Converting Enzyme Inhibitors; D000889:Anti-Arrhythmia Agents; D007211:Indoles; D007773:Lactates; D010725:Phosphocreatine; C053500:perindoprilat; D000255:Adenosine Triphosphate; D007703:Peptidyl-Dipeptidase A