KATP channel modulators and myocardial damages induced by ischemia-reperfusion:: Membrane lipids injury and arrhythmias

Although K-ATP channels have been proposed as playing a role in most types of myocardial damage associated with ischemia/reperfusion, the potential benefits of K-ATP channel modulators against the biochemical and electrical disturbances observed during ischemia remain unclear. We have thus studied the effects of glibenclamide and cromakalim, K-ATP channel blocker and opener respectively, on membrane lipid injury and arrhythmias, in a model of ischemic-reperfused guinea-pig myocardium. Ventricular strips were prelabeled with [H-3] arachidonic acid, then subjected to normal conditions (Time-related Control) or to simulated ischemic-reperfused conditions in absence of drug (Control) or in presence of glibenclamide 10 mu M or cromakalim 10 mu M. The release of radioactive compounds was counted by liquid scintillation spectrometry, while action potentials (AP) were recorded with intracellular microelectrodes. Reperfusion induced a significant increase of arachidonic acid release (P<0.05 Versus Time-related Control). Glibenclamide inhibited the reperfusion-induced arachidonic acid release while cromakalim only delayed it (respectively 483+/-87 dpm/g, P<0.05 and 790+/-143 dpm/g, NS versus 838+/-80 dpm/g for Control, after 30 min of reperfusion). Unlike glibenclamide, cromakalim was proarrhythmic during reperfusion (in 100% of preparations versus 33% in Control or in presence of glibenclamide, P<0.05). This in vitro study shows that glibenclamide prevented the reperfusion-induced membrane arachidonic acid release, without proarrhythmic effect, whereas cromakalim, associated with proarrhythmicity, was unable to protect myocardium from cell lipid damage. (C) 1998 Academic Press.