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 120 ± 5 cycles/min and aortic pressure changes were damped. The infarct size (necrotic volume/risk region volume x 100) was 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 was not due to changes in collateral flo