S. Picard et al., K-ATP channel modulators and myocardial damages induced by ischemia-reperfusion: Membrane lipids injury and arrhythmias, J MOL CEL C, 30(12), 1998, pp. 2613-2621
Although K-ATP channels have been proposed as playing a role in most types
of myocardial damage associated with ischemia/reperfusion, the potential be
nefits of K-ATP channel modulators against the biochemical and electrical d
isturbances observed during ischemia remain unclear. We have thus studied t
he effects of glibenclamide and cromakalim, K-ATP channel blocker and opene
r respectively, on membrane lipid injury and arrhythmias, in a model of isc
hemic-reperfused guinea-pig myocardium. Ventricular strips were prelabeled
with [H-3] arachidonic acid, then subjected to normal conditions (Time-rela
ted Control) or to simulated ischemic-reperfused conditions in absence of d
rug (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 del
ayed 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 glibencla
mide, cromakalim was proarrhythmic during reperfusion (in 100% of preparati
ons versus 33% in Control or in presence of glibenclamide, P<0.05). This in
vitro study shows that glibenclamide prevented the reperfusion-induced mem
brane arachidonic acid release, without proarrhythmic effect, whereas croma
kalim, associated with proarrhythmicity, was unable to protect myocardium f
rom cell lipid damage. (C) 1998 Academic Press.