THE ATP-DEPENDENT POTASSIUM CHANNEL - AN ENDOGENOUS CARDIOPROTECTIVE MECHANISM

The major objectives of the present study were to examine the effects of ischemic preconditioning and two endogenous substances, adenosine a nd acetylcholine (ACh), on myocardial infarct size to determine the ro le of the cardiac K-ATP channel in mediating these effects. Barbital-a nesthetized open-chest dogs subjected to 60 min of left anterior desce nding coronary artery (LAD) occlusion followed by 4 h of reperfusion w ere used. Preconditioning elicited by 10 min of LAD occlusion or intra coronary infusion of adenosine (400 mu g/min) or ACh (10 mu g/min) for 10 min, followed by 10 min of reperfusion or drug-free period before the 60-min occlusion period, markedly reduced myocardial infarct size to a similar extent compared to that in control dogs that were infused with an equivalent volume of saline into the LAD for 10 min followed by a 10-min saline-free period before the 60-min ischemic insult. The infarct size-limiting effects of these three endogenous interventions were totally abolished by the specific K-ATP-channel blockers glibencl amide or 5-hydroxydecanoate. These results indicate that cardiac K-ATP -channel activation is an important endogenous protectant against isch emia-reperfusion injury.