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Circulation. 1998;97:786-794

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(Circulation. 1998;97:786-794.)
© 1998 American Heart Association, Inc.


Basic Science Reports

Tachycardia Preconditions Infarct Size in Dogs

Role of Adenosine and Protein Kinase C

Raúl J. Domenech, MD; Pilar Macho, MD; Diego Vélez, MD; Gina Sánchez, BQ; Xueliang Liu, MD; ; Naranjan Dhalla, MD

From Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile (R.J.D., P.M., D.V., G.S.), and the Institute of Cardiovascular Sciences, Faculty of Medicine, University of Manitoba, Winnipeg, Canada (X.L., N.D.).

Correspondence to Dr Raúl J. Domenech, Facultad de Medicina, Campus Oriente, Universidad de Chile, Casilla 16038, Santiago 9, Chile.

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 volumex100) 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 flow 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. No changes in cytosolic or particulate protein kinase C activity or translocation of {alpha}-, ß-, {epsilon}-, and {zeta}- protein kinase C isozyme by effect of tachycardia or ischemia were observed between preconditioned and nonpreconditioned dogs.

Conclusions—Tachycardia, in 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.


Key Words: adenosine • myocardial infarction • preconditioning • protein kinase C




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