TACHYCARDIA PRECONDITIONS INFARCT SIZE IN DOGS - ROLE OF ADENOSINE AND PROTEIN-KINASE-C

Background-Myocardial ischemic preconditioning is a well-known phenome non, however there is scant information in regard to nonischemic preco nditioning. Methods and Results-We studied in anesthetized dogs the pr econditioning effect uf tachycardia and the mediation oi adenosine and protein kinase C in this process. In a control group the anterior des cending coronary artery was occluded for 60 minutes and reperfused for 270 minutes. Heart rate was kept constant at 112+/-5 cycles/min and a ortic pressure changes were damped. Tile 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 interve ning periods at control heart rate, were induced previous to the coron ary occlusion, The infarct size was reduced by 46% (P<.001) with respe ct 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 trans mural vasodilatory reserve was preserved, The blockade of adenosine re ceptors with 8 phenyltheophylline, before or after the preconditioning tachycardia, reverted its protecting effect but it did not modify inf arct size in nonpreconditioned dogs. Na changes in cytosolic or partic ulate protein kinase C activity or translocation of alpha-, beta-, eps ilon-, and zeta-protein kinase C isozyme by effect of tachycardia or i schemia were observed between preconditioned and nonpreconditioned dog s. Conclusions-Tachycardia, ill the absence of ischemia mimics the pre conditioning effect of ischemia in the dog. This effect is mediated by adenosine but not by changes in protein kinase C activity or its tran slocation.