COMPARATIVE EFFICACY OF ANTIARRHYTHMIC AGENTS IN PREVENTING HALOTHANE-EPINEPHRINE ARRHYTHMIAS IN RATS

Background: Because the relative efficacy of antiarrhythmic agents on halothane-epinephrine arrhythmias has not been well characterized, thi s study was undertaken to comparatively evaluate the antiarrhythmic ac tion of Na+-, K+- and Ca2+channel blockers on epinephrine-induced vent ricular arrhythmias during halothane anesthesia in rats. Methods: Rats were anesthetized at random with either halothane (1.5%), isoflurane (2.0%), or pentobarbital (50 mg/kg intraperitoneally), and the lungs w ere mechanically ventilated with oxygen. The rats were studied in thre e consecutive protocols. Protocol I determined the arrhythmogenic thre sholds of epinephrine during the three types of anesthesia in 33 rats. Protocol II determined the arrhythmogenic thresholds of epinephrine d uring halothane anesthesia in 64 rats receiving saline (control) or on e of five antiarrhythmic agents. Protocol III measured the duration of epinephrine-induced arrhythmias during halothane anesthesia in 42 rat s receiving saline (control) or one of five antiarrhythmic agents. Res ults. In protocol I, the arrhythmogenic doses of epinephrine during ha lothane, isoflurane, or pentobarbital anesthesia were 1.7 +/- 3.2, 11. 1 +/- 0.6, and 39.0 +/- 3.9 mug/kg, respectively, and the correspondin g plasma concentrations were 4.3 +/- 0.8, 103.7 +/- 9.2, and 246.7 +/- 28.9 ng/ml, respectively. In protocol II, the arrhythmogenic doses we re similar in rats receiving saline and in those receiving lidocaine. The arrhythmogenic doses in rats receiving verapamil, flecainide (Na+- and K+- channel blocker), E-4031(K+- channel blocker), or amiodarone( K+- channel blocker with Na+-, Ca2+-, and beta-blocking activity) incr eased significantly, i.e., 4.2, 4.2, 5.5, and 31.7 times control (P < 0.01). In protocol III, lidocaine had no effect on the duration of arr hythmias. Flecainide, E-4031, and verapamil markedly reduced the durat ion of arrhythmias induced by epinephrine, 8 mug/kg intravenously (P < 0.01), whereas only amiodarone markedly reduced the duration of arrhy thmias induced by epinephrine, 16 mug/kg intravenously (P < 0.01). Con clusions: It was concluded that agents with K+- channel blocking prope rties were the most effective in preventing halothane-epinephrine arrh ythmias in rats.