Exogenous bradykinin was administered to pigs in which an experimental infarction was evoked by ischemia and reperfusion. Ischemia (45 min) was induced in a closed-chest model with a balloon catheter in the left anterior descending artery, reperfusion by deflating and removing the balloon. The pigs were treated with saline (n = 11) or bradykinin (0.1 mg/kg in 30 min) infusion (n = 10) during the last 15 min of the ischemic period and the first 15 min of reperfusion. During ischemia, heart rate increased in the saline group to 120 +/- 9% of the initial value (p less than 0.05) and in the bradykinin group to 155 +/- 13% (p less than 0.05). After reperfusion, the rate-pressure product was increased in both groups. The increase of arterial creatine kinase levels was significantly less in the bradykinin-treated group. However, the catecholamine and purine levels were increased, as was the plasma renin activity when compared with the saline group. Two weeks after the infarction, six pigs had died in each group. In three out of five surviving saline-treated pigs and one out of four surviving bradykinin-treated pigs, a sustained ventricular tachyarrhythmia was inducible after programmed electrical stimulation. In conclusion, although systemically administered bradykinin caused a temporary increase in myocardial ischemia, it did reduce the (enzymatic indices of) infarct size. Therefore, the beneficial effects, previously found for ACE-inhibitors might at least partially be related to the potentiation of endogenous bradykinin.

Animals↗

PubMedDate not supplied

Sustained protection by iloprost of the porcine heart in the acute and chronic phases of myocardial infarction.

The effects of iloprost (ZK 36 374) on myocardial ischemia and infarction were studied in three groups of four anesthetized and heparinized pigs. Coronary microembolization was evoked by the injection of microspheres (50 microM) into the left coronary artery. A dose of 12 million beads/kg was followed by ventricular fibrillation and death after 11 +/- 5 min (group A). In group B, ischemia was evident at 15 min after the injection of 6 million beads/kg from an ST segment elevation in the precordial electrocardiogram (2.9 +/- 1.1 mV; p less than 0.05) and from an arterial-coronary venous difference in inosine concentration of -8.5 +/- 0.3 microM (p less than 0.05). However, in the presence of iloprost--an infusion of 0.18 micrograms/kg/min started 30 min before embolization--no ST segment elevation (0.45 +/- 0.23 mV; NS) or inosine release (-1.5 +/- 1.0 microM) was detected after the injection of 12 million beads/kg (group C). After 7 days, the animals from group B had more frequent spontaneous ventricular arrhythmias than those from group C. Programmed electrical stimulation induced intraventricular reentry in some animals of both groups (3 of 4 in B and 2 of 4 in C). Ventricular tachycardia was induced in two animals from group B. Postmortem examination revealed small myocardial infarcts in all group B animals; however, in group C no infarcts were detected. These data corroborate the view that prostacyclin-mimetic compounds are beneficial in the acute and in the chronic phases of myocardial infarction.

Animals↗

PubMedDate not supplied

Neurohumoral changes and the inducibility of ventricular tachycardias: effect of early reperfusion on the ischemic porcine myocardium.

The effects of early reperfusion were studied in closed-chest pigs subjected to either 45 min or 3 hr of regional ischemia. Myocardial enzyme release during early reperfusion and electrophysiological stability after two weeks were assessed. Coronary artery occlusion durations of 3 hr and early reperfusion after 45 min were compared. The creatine phosphokinase levels in the coronary effluent were lower after early reperfusion (p less than 0.001). Moreover, in the early reperfusion group, the coronary sinus catecholamine and purine levels rose to higher values than in the 3 hr group. The plasma levels of catecholamines and the plasma renin activity increased rapidly but transiently at reperfusion in the 45 min group. Both the rate-pressure product and the heart rate were elevated at the end of the reperfusion period (p less than 0.001) in the 45 min group. Survival for two weeks was 3 out of 6 animals in the 3 hr group and 5 out of 8 in the 45 min group. In all but one surviving animal, sustained ventricular tachycardias were inducible by programmed stimulation. Abnormally low QRS amplitudes and delayed potentials were found in the signal-averaged electrocardiogram in the early reperfusion group only. In conclusion, early reperfusion causes a reduction of myocardial tissue damage, but simultaneously, neurohumoral parameters showed a greater activation of the sympathetic nervous system and the renin-angiotensin system apparently causing a deleterious increase in oxygen consumption. Therefore, this injurious component of early reperfusion might prevent the potentially beneficial effects of a reduced tissue damage on survival or late arrhythmias.

Animals↗

PubMedDate not supplied

Reduction of reperfusion arrhythmias in the ischemic isolated rat heart by angiotensin converting enzyme inhibitors: a comparison of captopril, enalapril, and HOE 498.

The effects of the angiotensin converting enzyme (ACE) inhibitors captopril, enalapril, HOE 498, and its prodrug on reperfusion arrhythmias after 15 min of coronary ligation were investigated in the isolated rat heart. Drug concentrations were equipotent in their effect on angiotensin I pressor response. Furthermore, the effect of indomethacin on ACE inhibition with captopril was studied. Upon reperfusion, ventricular fibrillation occurred in all untreated hearts, in all prodrug HOE 498-treated hearts (15 micrograms/ml), and in 4 of 6 of the enalapril-treated (8 micrograms/ml) hearts. In contrast, in only 2 of 6 (p less than 0.002) of the HOE 498-treated hearts (15 micrograms/ml) and in none (p less than 0.001) of the captopril-treated hearts (80 micrograms/ml) did ventricular fibrillation occur. A massive purine overflow was observed in untreated hearts upon reperfusion. This overflow was significantly reduced by captopril and HOE 498, whereas enalapril and prodrug HOE 498 had no significant effect. Concomitantly, the pressure-rate index was severely impaired after 30 min of reperfusion in the untreated, enalapril, and prodrug HOE 498 groups (33 +/- 9, 52 +/- 11, and 48 +/- 12% of initial values, respectively), but captopril and HOE 498 significantly reduced the impairment of mechanical function (124 +/- 9% and 98 +/- 9%, respectively). In contrast to enalapril and prodrug HOE 498, captopril and HOE 498 markedly reduced noradrenaline overflow during the first minutes of reperfusion. No angiotensin II was detectable in the coronary effluent of untreated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗