Pharmacological preconditioning with the adenosine triphosphate-sensitive potassium channel opener pinacidil

Background. Ischemic preconditioning (IPC) decreases infarct size after glo bal or regional ischemia. Potassium channel openers also precondition but a re subject to dose-limiting vasodilation. We compared the mechanical and el ectrophysiological effects of ischemic and pharmacological preconditioning in an isolated rabbit heart model. Methods. Rabbit hearts were preconditioned with either 10 mu mol/L pinacidi l alone (P-), 10 mu mol/L pinacidil with 10 mu mol/L phenylephrine (Pf), or two cycles of global ischemia and reperfusion (IPC) before 1 hour of LAD o cclusion. Left ventricular pressure, epicardial monophasic action potential duration (APD) and coronary now were monitored throughout. Infarct size wa s determined at the end of reperfusion. Results. Regional ischemia uniformly decreased APD (p < 0.05). During reper fusion, APDs were prolonged beyond preischemic values in all preconditioned groups (p < 0.05). P- and Pf reduced the incidence of fibrillation. P- sig nificantly increased coronary flow (+15%, p 0.001), whereas IPC and P+ did not. However, IPC and P- significantly decreased systolic function (p < 0.0 5) but P+ did not. In addition, IPC depressed diastolic function (p < 0.05) but P- and P+ did not. Infarct size was reduced by all methods (p < 0.05). Conclusions. Pinacidil presents a safe and effective alternative to IPC for preserving the heart during regional ischemia. Its coronary vasodilatory e ffects are safely and effectively reversed by the addition phenylephrine. ( C) 2000 by The Society of Thoracic Surgeons.