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 t o determine the role of cardiac ATP-sensitive potassium (K(ATP)) chann els in mediating its effects. Barbital-anesthetized open-chest dogs we re subjected to 60 min of left anterior descending coronary artery (LA D) occlusion followed by 4 h of reperfusion. Preconditioning was elici ted by 10 min of LAD occlusion followed by 10 min of reperfusion befor e the 60-min occlusion period. ACh (10 mug/min) or an equivalent volum e 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 K(ATP) channel blocker glibenclamide (0.3 mg/kg iv) was g iven 15 min before ACh administration. Transmural myocardial blood flo w was measured at 30 min of occlusion, and infarct size (IS) was deter mined by triphenyltetrazolium staining and expressed as a percentage o f the anatomic area at risk (AAR). There were no significant differenc es in hemodynamics, collateral blood flow, or AAR between groups. Prec onditioning 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, r esulted in a dramatic decrease in IS (10.0 +/- 2.9%), whereas glibencl amide completely abolished its protective effects (20.9 +/- 4.8%). The se results are the first to indicate that ACh mimics ischemic precondi tioning via a cardiac K(ATP) channel-sensitive mechanism in dogs.