ADDITIVE CARDIAC DEPRESSION BY VOLATILE ANESTHETICS IN ISOLATED HEARTS AFTER CHRONIC AMIODARONE TREATMENT

Some patients undergoing general anesthesia may be chronically receivi ng the antidysrhythmic drug amiodarone. The half-life of this drug is very long and it may not be advisable or possible to discontinue its a dministration prior to anesthesia. We examined depressant effects of t hree volatile anesthetics in hearts isolated from guinea pigs chronica lly treated with amiodarone. Hearts were isolated and perfused retrogr adely through the aorta with oxygenated Krebs-Ringer solution at 37 de grees C at constant pressure. Variables measured in 26 hearts were hea rt rate (HR), atrioventricular, intraatrial, and intraventricualr cond uction times (AVCT, IACT, IVCT) during pacing at 240 bpm, coronary flo w, and left ventricular pressure (LVP). Amiodarone (20 mg intraperiton eally) or placebo (Group 1) was given once daily for 1 (Group 2) or 4 (Group 3) wk. Cardiac tissue concentrations of amiodarone were similar (12.1 mu g/g wet weight) in hearts in Groups 2 and 3 but serum levels were twice as high in hearts in Group 3 as in Group 2 (0.33 vs 0.17 m u g/mL). Before anesthetic exposure, all variables for hearts in Group 2 were not significantly different from those in Group 1. Significant ly, for hearts in Group 3, compared to those in Group 1, HX was slower (-14%), conduction times were longer (IACT + 5 ms, IVCT + 4 ms, AVCT + 9 ms), coronary flow was higher (+23%), and LVP was lower (-12%). Af ter control measurements, hearts were exposed to 0.5 and 1 minimum alv eolar anesthetic concentration (MAC) halothane, enflurane, and isoflur ane in random order. Each anesthetic slowed HR, prolonged IACT and AVC T, and decreased LVP in a dose-dependent manner; only isoflurane incre ased flow in a dose-dependent manner. Enflurane depressed HR and LVP m ore than halothane or isoflurane, halothane decreased LVP more than is oflurane, and isoflurane increased coronary flow more than halothane o r enflurane. The changes in these variables due to anesthetic effects were statistically additive to the changes due to amiodarone. Our resu lts indicate that all three anesthetics augment cardiac depression due to chronic administration of amiodarone. This study in isolated heart s suggests that patients on chronic amiodarone therapy for dysrhythmia s may exhibit pronounced impairment of conduction and contractility, e specially with enflurane, and augmented coronary vasodilation, especia lly with isoflurane.