Chronic alcohol consumption has been shown to induce a cardiomyopathy which appears to be directly correlated with the duration and quantity of alcohol that is consumed. Along with changes in cardiac mechanical function and morphology, there also appear to be changes in the cardiac conduction system. However, before overt changes in myocardial contraction, morphology or conduction have been manifested, alterations may have already occurred that make the myocardium more susceptible to injury by a second stress. Ischemia and reperfusion of the myocardium is a stress to the heart that results in many cardiac deaths not only because of mechanical damage to the heart but also because cardiac arrhythmias are a major consequence of both the ischemic insult and the reperfusion condition. The hypotheses to be tested in this pilot proposal are that ischemic insult and the potentiates arrhythmias induced either by ischemia and reperfusion or by isoproterenol administration mild oxidant stress seems to initiate the development of protective mechanisms in the myocardium that may produce better tolerance to a second oxidant stress. For example, pretreatment of an animal with a mild dose of endotoxin 24 hrs prior to an ischemia/reperfusion insult results in better recovery of ventricular function of the endotoxin treated than of the control treated groups. Thus, we propose in this pilot study to determine the effects of chronic alcohol consumption (8-10 weeks), with alcohol as 36% of the caloric intake, on the severity of arrhythmias induced by ischemia by ischemia and reperfusion or by high doses of isoproterenol. In other groups of animals the effects of the acute administration of alcohol, to achieve blood levels of approximately 200 mg/dl, on ischemia and reperfusion induced arrhythmias or isoproterenol induced arrhythmias will be determined. Finally, the possible attenuation of ischemia/reperfusion and isoproterenol induced arrhythmias by 24 hour pretreatment with endotoxin will be assessed. Al of these studies will be performed in vivo, in anesthetized rats in which blood pressure, heart rate and the electrocardiogram will be monitored continuously. The severity of the arrhythmic changes will be quantitated by determining initial changes in ventricular rhythm, ventricular tachycardia and finally ventricular fibrillation. Both time to initiation of rhythm disturbances and duration of rhythm disturbances will be quantitated to achieved an arrhythmia severity index as reported by other investigators studying arrhythmogenicity.
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