Acetylcholine mimics ischemic preconditioning via a glibenclamide-sensitive mechanism in dogs.
The major objectives of the present study were to examine the ability of acetylcholine (ACh) to mimic ischemic preconditioning in dogs and to determine the role of cardiac ATP-sensitive potassium (KATP) channels in mediating its effects. Barbital-anesthetized open-chest dogs were subjected to 60 min of left anterior descending coronary artery (LAD) occlusion followed by 4 h of reperfusion. Preconditioning was elicited by 10 min of LAD occlusion followed by 10 min of reperfusion before the 60-min occlusion period. ACh (10 micrograms/min) or an equivalent volume of saline were infused into the LAD for 10 min followed by a 10-min drug-free period before the 60-min ischemic insult. In another group, the specific KATP channel blocker glibenclamide (0.3 mg/kg iv) was given 15 min before ACh administration. Transmural myocardial blood flow was measured at 30 min of occlusion, and infarct size (IS) was determined by triphenyltetrazolium staining and expressed as a percentage of the anatomic area at risk (AAR). There were no significant differences in hemodynamics, collateral blood flow, or AAR between groups. Preconditioning produced a marked reduction (P < 0.05) in IS (5.3 +/- 3.0 vs. 23.7 +/- 5.9% in the controls). ACh, similar to preconditioning, resulted in a dramatic decrease in IS (10.0 +/- 2.9%), whereas glibenclamide completely abolished its protective effects (20.9 +/- 4.8%). These results are the first to indicate that ACh mimics ischemic preconditioning via a cardiac KATP channel-sensitive mechanism in dogs.
Yao
Z
Z
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Gross
G J
GJ
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology*; D012008:Recurrence; D014693:Ventricular Fibrillation / Q000209:etiology
D000109:Acetylcholine; D005905:Glyburide