Background. The accurate performance of coronary anastomoses on the beating heart requires some form of myocardial immobilization that can be achieved pharmacologically. Different classes of drugs can be used to induce bradycardia, but the most effective in this setting of off-pump operation has not yet been determined. Methods. Fifty-six isolated buffer-perfused rabbit hearts were divided into seven equal groups. Control hearts were continuously perfused throughout the experimental time course. A second group of hearts underwent 60 minutes of potassium arrest (at 37°C) followed by 1 hour of reperfusion. The following pharmacologic approaches were tested in the remaining five groups: shortacting β-blockade (esmolol, 6 x 10-3 mol/L and 3 x 10-4 mol/L), opening of adenosine triphosphate-dependent potassium channels (nicorandil, 10-3 mol/L and 10-5 mol/L), and inhibition of the pacemaker current, which largely accounts for the diastolic depolarization of sinoatrial node cells (S 16257-2, 3 x 10-6 mol/L). Each drug was infused at a constant rate for 60 minutes, after which hearts were perfused for 1 additional hour with drug-free buffer. Heart rate and isovolumic measurements of function and coronary flow were serially taken during and after drug infusion. Results. The worst recovery of systolic and, moreover, diastolic function was yielded by potassium arrest. Neither esmolol nor nicorandil was able to induce a significant bradycardia. However, nicorandil did not impair function which, conversely, was markedly depressed after esmolol therapy. Significant bradycardia (p < 0.0001 versus corresponding baseline values and versus all other groups) was only achieved with pacemaker current inhibition, which was otherwise associated with an excellent preservation of contractility, diastolic function, and coronary flow. Conclusions. Inhibition of the pacemaker current seems to be an effective approach for inducing intraoperative bradycardia without compromising left ventricular function or flow.