X. Kong, J. S. Tweddell, G. J. Gross and J. E. Baker. Sarcolemmal and Mitochondrial K(
ATP)Channels 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 K(
ATP)channels. Rabbits (n=8/group) were raised from birth in a normoxic (F(I)O(2)=0.21) or hypoxic (F(I)O(2)=0.12) environment for 8-10 days and the heart perfused with Krebs-Henseleit
bicarbonate buffer. A mitochondrial-selective K(
ATP)channel blocker
5-hydroxydecanoate (5-HD) (300 micromol/l) or a sarcolemmal-selective K(
ATP)channel blocker
HMR 1098 (30 micromol/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 K(
ATP)channels contribute to cardioprotection in the chronically hypoxic heart.