Differential Protective Effects of Halothane and Isoflurane Against Hypoxic and Reoxygenation Injury in the Isolated Guinea Pig Heart

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Abstract
The authors investigated the effects of halothane (HAL) and isoflurane (ISO) on cardiac depression produced by global hypoxia and the recovery of function following reoxygenation in isolated guinea pig hearts perfused with Krebs'' solution at constant pressure. Isovolumetric left ventricular systolic (LVSP) and end-diastolic pressures (LVEDP) were measured by placing a saline filled, latex balloon into the left ventricle. Bipolar electrodes were placed in the right atrium and right ventricle for measurement of heart rate (HR), atrioventricular conduction time (AVCT), and determination of the incidence and severity of dysrhythmias occurring during hypoxia and reoxygenation. Hearts were divided into three groups: control (n = 20), halothane (n = 12), and isoflurane (n = 13). All hearts were exposed in sequence to oxygenated perfusate (PO2, 530 mmHg), moderately hypoxic perfusate (PO2, 91 mmHg) for 30 min, and then to oxygenated perfusate for 40 min. Halothane (1%, 0.4 mM) or isoflurane (1.5%, 0.5 mM) were administered 10 min before hypoxia, during hypoxia, and during the first 10 min of reoxygenation. Exposure to halothane and isofluorane before hypoxia produced a 14 and 11% decrease in heart rate, a 32 and 23% increase in AVCT, and a 47 and 28% decrease in LVSP (all P <LEQ 0.001) for halothane and isoflurane, respectively, and no significant change in LVEDP. During hypoxia, HR decreased AVCT increased similarly in both groups. Left ventricular systolic pressure (LVSP) decreased sharply with a narrowing of the prehypoxic differences among the groups. In the control and isoflurane groups, LVEDP increased during hypoxia but remained unchanged in the halothane group. After 40 min of reoxygenation, LVEDP in the control group (11 .+-. 3 mmHg) was significantly higher than in the halothane group (0.5 .+-. 1.0 mm Hg) but not significantly different from the isoflurane group (5.5 .+-. 3.0 mmHg). Halothane reduced the incidence of ventricular tachycardia from 80 to 42% and of ventricular fibrillation from 70 to 17% during the 30-min period of hypoxia and during the first 30 min of reoxygenation, respectively, and produced a threefold increase in the average time the hearts were in sinus rhythm. The results indicate that halothane protects the isolated heart against hypoxic damage as assessed by improved recovery of LVSP, reduced LVEDP, and reduced incidence and duration of dysrhythmias during hypoxia and reoxygenation. The mechanism of protection by halothane could be related to reduced cardiac work before and after hypoxia or possibly to other direct protective myocardial cellular effects.