Adaptation to high altitude hypoxia protects the rat heart against ischemia-induced arrhythmias.: Involvement of mitochondrial KATP channel

The aim was to determine whether adaptation to chronic hypoxia protects the heart against ischemic arrhythmias and whether ATP-dependent potassium channels (K-ATP) play a role in the antiarrhythmic mechanism. Adult male rats were adapted to intermittent high altitude hypoxia (5000 m, 4 h/day) and susceptibility to ischemia-induced ventricular arrhythmias was evaluated in the Langendorff-perfused hearts subjected to either an occlusion of the coronary artery for 30 min or pre-conditioning by brief occlusion of the same artery prior to 30-min reocclusion. In separate groups, either a K-ATP blocker, glibenclamide (10 mu mol/ l), or a mitochondrial K-ATP opener, diazoxide (50 mu mol/l), were added to a perfusion medium 20 min before the occlusion. Adaptation to hypoxia reduced the total number of ventricular arrhythmias by 64% as compared with normoxic controls, Preconditioning by a single 3-min coronary artery occlusion was antiarrhythmic only in the normoxic group, while two occlusion periods of 5 min each were needed to pre-condition the hypoxic hearts. Glibenclamide increased the number of arrhythmias in the normoxic hearts from 1316+/-215 to 2091+/-187 (by 59%) and in the hypoxic group from 636+/-103 to 1777+/-186 (by 179%). In contrast, diazoxide decreased the number of arrhythmias only in the normoxic group from 1374+/-96 to 582+/-149 (by 58%), while its effect in the hypoxic group was not significant. It is concluded that long-term adaptation of rats to high altitude hypoxia decreases the susceptibility of their hearts to ischemic arrhythmias and increases an antiarrhythmic threshold of pre-conditioning. The mitochondrial K-ATP channel, rather than the sarcolemmal K-ATP channel, apears to be involved in the protective mechanism afforded by adaptation. (C) 1999 Academic Press.