CROMAKALIM AND CICLETANINE AGAINST PACING-INDUCED MYOCARDIAL-ISCHEMIAIN CONSCIOUS RABBITS

Myocardial ischemia assessed by intracavital ST-segment elevation, sho rtening of ventricular effective refractory period (VERP), and increas e in left ventricular end-diastolic pressure (LVEDP) was provoked by v entricular overdrive pacing (VOP) in conscious rabbits. Cromakalim (10 mu g/kg), an ATP-sensitive K+ channel opener, and cicletanine (30 mg/ kg), a cGMP-phosphodiesterase inhibitor, reduced VOP-induced ST-segmen t elevation and LVEDP-increase. Under resting conditions, cromakalim l owered blood pressure, increased heart rate (HR), and shortened VERP, whereas cicletanine decreased HR, prolonged VERP without changing bloo d pressure. Co-administration of cromakalim and cicletanine additively reduced VOP-induced ST-segment elevation, shortening of VERP, and LVE DP-increase. Cicletanine did not change cromakalim-induced hypotension but abolished reflexogenic tachycardia. This suggests that VERP short ening is not a prerequisite for the anti-ischemic effect of cromakalim , and the combination of these drugs may afford a potent and safe anti -ischemic effect without affecting hypotension induced cromakalim.