BACKGROUND: Calcium channel blockers and volatile anesthetics have depressant effects on cardiac function. Both of them appear to exert, qualitatively and quantitatively, different effects on myocardial contractility, coronary flow, and myocardial oxygen balance. The aim of this study was to examine the direct cardiac effects of the enflurane in the presence of diltiazem. METHODS: Isolated Sprague-Dawley rat hearts (N=45) were perfused at constant pressure with oxygenated Modified-Krebs solution (pH 7.4, 37oC). Isovolumetric left ventricular pressure (LVP) and dP/dt were measured via a latex balloon and transducer. Also, coronary flow and oxygen tensions at the coronary inflow and outflow were measured. After stabilization period, all hearts were subjected to the application with diltiazem (100 ng/ml). Thereafter, they were subdivided into three groups; group 1, 2, 3. Groups subjected to the combination of diltiazem (100 ng/ml) with enflurane 1.1, 2.2, or 3.3 vol%, respectively. RESULTS: After the application of diltiazem, myocardial contractility and heart rate were significantly decreased, and coronary flow were significantly increased. The combination of diltiazem with enflurane depressed myocardial contractility, heart rate, myocardial O2 consumption, and percentage of O2 extraction more than diltiazem alone, and their effects were dependent on the concentration of enflurane. However, there was no difference in the change of coronary flow and oxygen delivery between diltiazem and the combination of diltiazem with enflurane. CONCLUSIONS: These in vitro findings demonstrate that the combination of diltiazem with enflurane shows greater direct negative inotropic and negative chronotropic effect, and is associated with less attenuation of coronary autoregulation, but with a larger reduction in O2 utilization. The present results suggest that high enflurane anesthesia in the diltiazem-pretreated patients could result in profound cardiac depression.