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 and acetylcholine (ACh), on myocardial infarct size to determine the role of the cardiac KATP channel in mediating these effects. Barbital-anesthetized open-chest dogs subjected to 60 min of left anterior descending coronary artery (LAD) occlusion followed by 4 h of reperfusion were used. Preconditioning elicited by 10 min of LAD occlusion or intracoronary infusion of adenosine (400 micrograms/min) or ACh (10 micrograms/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 KATP-channel blockers glibenclamide or 5-hydroxydecanoate. These results indicate that cardiac KATP-channel activation is an important endogenous protectant against ischemia-reperfusion injury.
Yao
Z
Z
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Gross
G J
GJ
D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D003327:Coronary Disease; D003652:Decanoic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; D000241:Adenosine; D000109:Acetylcholine; D005905:Glyburide