Protective effect of 17beta-Estradiol Against Reperfusion Arrhythmias in Cats

ABSTRACT

BACKGROUND: Although reperfusion certainly prevents tissue ischemia from possible cardiac death, several lines of evidence suggest that reperfusion may paradoxically aggravate the frequency of serious reperfusion-induced lethal arrhythmias. It has been reported that acute administration of estrogen at physiological concentrations reduced with myocardial ischemic injury in women with coronary heart disease. In studies with canines, acute administration by either the intra-muscular or the intra-coronary route similarly prevented ischemia and reperfusion dysrhythmias and also reduced the infarct size because the estrogen increased the distal coronary perfusion pressure, scavenged free radicals and had other effects during both ischemia and reperfusion. However, the canine heart is notoriously well collateralized. 17beta-estradiol induces very little vasorelaxation in cat coronary rings, suggesting that increased ischemic myocardial blood flow dose not contribute to the protective effect. In the present study, employing a cat model of regional cardiac ischemia, we examined whether reperfusion rendered after acute administration of 17beta-estradiol could lower the incidence of reperfusion-induced lethal arrhythmia and the death rate. METHOD: Adult mongrel male cats(n=31, 2.7~4.5 kg) were anesthetized under positive-pressure artificial ventilation with room air. Electrocardiograms were recorded. The animals of the control group(n=15) were subjected to 20-minute left anterior descending coronary artery(LAD) occlusion followed by abrupt reperfusion. The animals in the experimental 17beta-estradiol(2 or 20 microgram/kg) group were subjected to ischemia/reperfusion insult following drug treatment 17beta-estradiol was applied intravenously within the 60 seconds just before LAD ligation followed by abrupt reperfusion. The Fisher's exact test was used to compare the data from different animal groups(p<0.05). RESULTS: The number of arrhythmias(ventricular premature beat, ventricular tachycardia and ventricular fibrillation) emerging during the reperfusion phase were not statistically different from that in the control group. The death rate in the 17beta-estradiol 20 microgram/kg group was lower from that in the control group(P value = 0.039). CONCLUSION: Acute administration of 17beta-estradiol at a supraphysiological concentration might produce cardioprotective effects, not by modificating the coronary blood flow into the threatened myocardial region, but by other mechanisms that directly or indirectly increase the intrinsic myocardial ischemic tolerance in the cat during the reperfusion phase.