The effects of oral pretreatment with zofenopril, an angiotensin-converting enzyme inhibitor, on early reperfusion and subsequent electrophysiologic stability in the pig.

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)