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

Domenech R.J.; Macho P; Vélez D.; Sánchez G; Liu, X; Dhalla N.

Keywords: model, size, enzyme, heart, fibrillation, animals, flow, blood, protein, cell, infarction, pressure, ischemia, electrocardiogram, velocity, experiment, artery, male, vessels, dogs, time, aorta, tissue, reperfusion, female, adenosine, article, kinase, coronary, tachycardia, dog, ischemic, activity, hemodynamic, animal, factors, c, left, processes, priority, p1, Rate, nonhuman, journal, Receptors,, diastole, Ventricular, Ventricles, Myocardial, purinergic, Systole, Dysfunction,, Preconditioning,

Abstract

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 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 ?-, ?-, ?-, and ?- 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.

Más información

Título de la Revista: CIRCULATION
Volumen: 97
Número: 8
Editorial: LIPPINCOTT WILLIAMS & WILKINS
Fecha de publicación: 1998
Página de inicio: 786
Página final: 794
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-0032478164&partnerID=q2rCbXpz