Rm. Fyer et al., Mitochondrial K-ATP channel opening is important during index ischemia andfollowing myocardial reperfusion in ischemic preconditioned rat hearts, J MOL CEL C, 33(4), 2001, pp. 831-834
We have previously demonstrated that K-ATP channel openers administered jus
t prior to and throughout reperfusion induce cardioprotection in the blood-
perfused canine heart, However, a recent report suggests that the mitochond
rial K-ATP channel is only a trigger of ischemic preconditioning (TPC). The
se recent data are, however, in contrast to most previous investigations th
at suggested that activation of the mitochondrial K-ATP channel is an impor
tant downstream mediator of cardioprotection. Therefore, we examined the ro
le of the mitochondrial K-ATP channel as a downstream mediator of IPC in a
rat model by administering the selective mitochondrial It, channel antagoni
st, 5-hydroxydecanoate (5-HD), at several points during IPC. Infarct size (
IS) was determined by tetrazolium chloride staining and expressed as a perc
ent of the area at risk (AAR). Control animals had an IS/AAR of 58.4 +/- 0.
6 and IS/AAR was reduced to 6.2 +/- 1.7 following IPC, 5-HD (10 mg/kg), att
enuated cardioprotection when administered either 5 min prior to the IPC st
imulus (40.4 +/- 1.4), during the reperfusion phase of the IPC stimulus (39
.7 +/- 5,9), or 5 min prior to reperfusion during prolonged ischemia (34.3
+/- 6.9). Additionally, when 5-HD was administered at 5 mg/kg during the re
perfusion phase of index ischemia plus 5 min prior to IPC or plus during th
e reperfusion phase of IPC, cardioprotection was also attenuated (36.3 +/-
5.5 and 43.8 +/- 6.9, respectively). These data suggest that activation of
the mitochondrial It,, channel is an important downstream regulator of myoc
ardial protection with effects lasting into the reperfusion period followin
g prolonged ischemia, (C) 2001 Academic Press.