Cromakalim is a member of the new
antihypertensive drug family possessing an action that involves an increased K efflux in vascular and cardiac muscle. We studied the contribution of opening of
ATP-sensitive K channel to the development of reperfusion-induced arrhythmias and myocardial ion shifts, particularly that of Na, K, Ca and Mg in isolated rat hearts. After 30 min of global
ischemia,
cromakalim (1 to 30 microM) failed to reduce reperfusion arrhythmias. On the postischemic-reperfused myocardium in a subset of hearts unresponsive to reperfusion-induced arrhythmias (duration of
ischemia was reduced to 25 min),
cromakalim treatment was associated with a higher incidence of reperfusion
ventricular fibrillation (VF) and
ventricular tachycardia (VT) as compared to the controls (100% VF and 100% VT in treated vs. 41% VF and 50% VT in controls, P < .05). Proarrhythmic effects of
cromakalim were also reflected in a maldistribution of myocardial
ions. At concentrations of 3, 10 and 30 microM of
glibenclamide, a K channel blocker, a significant reduction in the incidence of reperfusion-induced VF and VT was observed, and an attenuation in the maldistribution of myocardial ion contents induced by
ischemia/reperfusion was found. The reduction in myocardial contractility was detected at relatively high concentrations (10 and 30 microM) in both
cromakalim- and
glibenclamide-treated groups. The proarrhythmic effect of
cromakalim (30 microM) was abolished by 3 microM of
glibenclamide, suggesting that the increased tendency to develop reperfusion arrhythmias is associated with the
cromakalim-induced K efflux.(ABSTRACT TRUNCATED AT 250 WORDS)