Tachycardia preconditions infarct size in dogs -: Role of adenosine and protein kinase C

Background-Myocardial ischemic preconditioning is a well-known phenomenon, however there is scant information in regard to nonischemic preconditioning. Methods and Results-We studied in anesthetized dogs the preconditioning effect of tachycardia and the mediation of adenosine and protein kinase C in this process. In a control group the anterior descending coronary artery was occluded for 60 minutes and reperfused for 270 minutes. Heart rate was kept constant at 112+/-5 cycles/min and aortic pressure changes were damped. The infarct size (necrotic volume/risk region volume x 100) war 15.8+/-1.5%. In another group of dogs a similar protocol was followed, but five periods of tachycardia (213+/-12 cycles/min), 5 minutes in duration each, with 5 minutes of intervening periods at control heart rate, were induced previous to the coronary occlusion, The infarct size was reduced by 46% (P<.001) with respect to the nonpreconditioned group. This effect war not due to changes in collateral now nor risk region size, During tachycardia, myocardial interstitial adenosine increased about twofold (P<.05); no metabolic, hemodynamic, or ECG evidences of ischemia were observed and the transmural vasodilatory reserve was preserved, The blockade of adenosine receptors with 8 phenyltheophylline, before or after the preconditioning tachycardia, reverted its protecting effect but it did not modify infarct size in nonpreconditioned dogs. Na changes in cytosolic or particulate protein kinase C activity or translocation of alpha-, beta-, epsilon-, and zeta-protein kinase C isozyme by effect of tachycardia or ischemia were observed between preconditioned and nonpreconditioned dogs. Conclusions-Tachycardia, ill the absence of ischemia mimics the preconditioning effect of ischemia in the dog. This effect is mediated by adenosine but not by changes in protein kinase C activity or its translocation.