BACKGROUND: Calcium channel blockers and volatile anesthetics have depressant effects on myocardial contractility by limiting Ca2+ entry and altering intracellular Ca2+ release. The aim of this study was to compare the direct cardiac effects of isoflurane, desflurane and new volatile anesthetics, sevoflurane, in combination with diltiazem on the isolated rat heart. METHODS: Sprague-Dawley rat hearts (N = 60) were isolated and perfused with oxygenated modified Krebs solution at 55 mmHg with 0.5, 1, 2 MAC of isoflurane, desflurane or sevoflurane in combination with diltiazem 42 ng/ml (group 1) and 84 ng/ml (group 2). Isovolumetric left ventricular pressure (LVP), rate of change ventricular pressure (dP/dt), heart rate and coronary flow were measured. To examine the indirect metabolic effect due to autoregulation of coronary flow, O2 delivery (DO2), myocardial O2 consumption (MVO2) and percent O2 extraction (POE) were also monitored. RESULTS: Diltiazem plus volatile anesthetics depressed LVP and dP/dt and increased coronary flow dose-dependently. They also decreased heart rate. In the group 2, at 2 MAC of inhaled anesthetics heart rate was significantly decreased than group 1. There were no statistical significance between isoflurane, desflurane and sevoflurane on myocardial contractility and myocardial oxygenation. CONCLUSIONS: These in vitro RESULTS demonstrate that clinical dose of diltiazem plus isoflurane, desflurane or sevoflurane has similar effects on myocardial contractility and coronary flow.