BACKGROUND: Propofol, an intravenous anesthetic agent, is known to have potential beneficial cardiac effects through a cardiac L-type calcium channel blocking effect and free radical scavenging activities in a number of myocardial stunning models at clinical concentrations. We investigated the effect of high doses of propofol on myocardium in the isolated rat heart to find out whether it has a cardiac protective effect on a normal, not stunning, conditioned heart. METHODS: Twenty male Sprague-Dawley rats were put under general anesthesia to monitor the heart and perfused with a modified Krebs solution with a Langendorff model. After 30 minutes of stabilization, isolated rat hearts were given 0.5, 1, 5, 10, 50, 100 and 250 micrometer of propofol in an increasing manner for 10 minutes, respectively. At every period, left ventricular pressure, dp/dt, heart rate and coronary flow were recorded and Na+ , K+ , Ca2+ , Mg2+ and protein leakage in the effluent perfusate were measured to observe the myocardial cell damage. RESULTS: Significant negative inotropic and chronotropic effects were seen at higher than 100 micrometer. Propofol dose-dependently increased coronary flow at concentrations of 100 micrometer or lower. Marked potassium and protein leakage in the effluent perfusate were found at a higher concentration of 100 micrometer propofol. CONCLSIONS: These findings suggest that a high dose of propofol exerts direct myocardial depression and myocardial cell damage, instead of a protective effect, in the isolated rat heart.