Anesthesia and surgery in the presence of recent myocardial infarction entails increased risk of mortality but is occasionally required for life threatening disease. The proposed study will examine the interaction between the commonly employed volatile anesthetics halothane, enflurane and isoflurane and the pathologic properties of ischemic Purkinje fibers associated with the generation of potentially lethal arrhythmias. The one-day-old canine infarction model to be employed is widely utilized in investigations of the effects of the antiarrhythmic drugs on ischemic cardiac tissues. Our preliminary studies indicate that halothane inhibits automaticity and triggered activity in this model, by decreasing the spontaneous rate, while simultaneously facilitating the generation of re-entrant antiarrhythmic drugs on ischemic cardiac triggered activity in this model, by decreasing the spontaneous rate, while simultaneously facilitating the generation of re-entrant arrhythmias. The hypothesis to be tested is that the volatile anesthetics influence the occurrence of ischemia related arrhythmias by their differential actions on the transmembrane currents associated with generation of the action potential in nonischemic and ischemic Purkinje fibers. The specific objectives are: 1) To determine in vitro the electrophysiologic properties of subendocardial Purkinje fibers in the one-day-old infarcted canine heart associated with the occurrence of dysrhythmias due to abnormal impulse generation and conduction. 2) To compare in vitro the actions of the volatile anesthetics on the action potential and refractory characteristics of Purkinje fibers in noninfarcted and infarcted canine hearts and to correlate these actions with their effects on the spontaneous ventricular arrhythmias observed in infarcted animals in vivo. 3) To directly measure the changes in the transsarcolemmal membrane currents and intracellular free calcium transient associated with exposure of nonischemic and ischemic Purkinje fibers to the anesthetic agents utilizing single Purkinje fiber voltage clamping techniques and intracellularly injected bioluminescent protein aequorin. The anesthetic management of patients with ischemia related perioperative arrhythmias is at present entirely empirical. The proposed study is designed to fill a gap in our knowledge regarding the interaction of the modern volatile anesthetics and the mechanisms known to underlie the generation of ischemia related arrhythmias.
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