Sarcolemmal and Mitochondrial KATPChannels Mediate Cardioprotection in Chronically Hypoxic Hearts

X. Kong, J. S. Tweddell, G. J. Gross and J. E. Baker. Sarcolemmal and Mitochondrial KATPChannels Mediate Cardioprotection in Chronically Hypoxic Hearts. Journal of Molecular and Cellular Cardiology (2001) 33, 1041–1045. Hypoxia from birth increases the resistance of the isolated neonatal heart to ischemia. We determined if increased resistance to ischemia was due to activation of sarcolemmal or mitochondrial KATPchannels. Rabbits (n=8/group) were raised from birth in a normoxic (FIO2=0.21) or hypoxic (FIO2=0.12) environment for 8–10 days and the heart perfused with Krebs–Henseleit bicarbonate buffer. A mitochondrial-selective KATPchannel blocker 5-hydroxydecanoate (5-HD) (300 μ mol/l) or a sarcolemmal-selective KATPchannel blocker HMR 1098 (30μ mol/l) were added alone or in combination for 20 min prior to a global ischemic period of 30 min, followed by 35 min reperfusion. Recovery of ventricular developed pressure was higher in chronically hypoxic than normoxic hearts. 5-HD and HMR 1098 partially reduced the cardioprotective effect of chronic hypoxia, but had no effect in normoxic hearts. The combination of 5-HD and HMR 1098 abolished the cardioprotective effect of chronic hypoxia. We conclude that both sarcolemmal and mitochondrial KATPchannels contribute to cardioprotection in the chronically hypoxic heart.