1. The effects of oral pretreatment with zofenopril, an angiotensin-converting enzyme inhibitor, on early reperfusion and subsequent electrophysiologic stability in the pig.
- Author
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Tio RA, de Langen CD, de Graeff PA, van Gilst WH, Bel KJ, Wolters KG, Mook PH, van Wijngaarden J, and Wesseling H
- Subjects
- Administration, Oral, Angiotensin-Converting Enzyme Inhibitors administration & dosage, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Animals, Captopril administration & dosage, Captopril pharmacology, Captopril therapeutic use, Coronary Disease enzymology, Coronary Disease prevention & control, Creatine Kinase blood, Electric Stimulation, Heart drug effects, Heart physiology, Heart Rate drug effects, Hemodynamics drug effects, Male, Myocardial Infarction drug therapy, Myocardial Infarction prevention & control, Myocardial Reperfusion Injury enzymology, Myocardium enzymology, Myocardium metabolism, Purines metabolism, Renin blood, Swine, Tachycardia drug therapy, Tachycardia prevention & control, Time Factors, Ventricular Function drug effects, Ventricular Function physiology, Angiotensin-Converting Enzyme Inhibitors pharmacology, Captopril analogs & derivatives, Myocardial Reperfusion Injury prevention & control
- Abstract
The effects of oral zofenopril pretreatment were investigated in a chronic closed-chest pig model of ischemia and reperfusion. Pigs (25-35 kg) were pretreated orally with zofenopril (15 mg/day) on the 2 days prior to ischemia, which was evoked by the inflation of a catheter balloon in the left anterior descending coronary artery over 45 minutes. The catheter was then removed and the myocardium was reperfused. After 2 weeks, infarct properties were assessed by signal averaging of the body surface electrocardiogram and the inducibility of malignant ventricular tachyarrhythmias was tested with a programmed electrical stimulation protocol. A significant increase in the pressure-rate product (43 +/- 11%, mean +/- SEM), indicating the oxygen demand of the heart, was prevented by zofenopril (19 +/- 8%, p less than 0.05). Zofenopril reduced the peak efflux of adrenaline (1302 +/- 213 vs. 3201 +/- 760 pg/ml; p less than 0.05), noradrenaline (402 +/- 54 vs. 902 +/- 282 pg/ml; p less than 0.05), and of the adenosine catabolites inosine and hypoxanthine (56 +/- 4 vs. 78 +/- 9, pg/ml; p less than 0.05) in the coronary venous effluent. The efflux of the cytoplasmatic enzyme creatine phosphokinase was not significantly reduced after zofenopril (p = 0.08). No difference in plasma renin levels between the groups were found. After 2 weeks, late potentials were found only in the surviving animals from the untreated group, i.e., the voltage vector magnitude was more reduced, and a prolongation of the QRS duration and of the terminal low-amplitude part of the high-frequency QRS were found.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1990
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