ADENOSINE SLOWS THE RATE OF K-INDUCED MEMBRANE DEPOLARIZATION IN VENTRICULAR CARDIOMYOCYTES - POSSIBLE IMPLICATION IN HYPERKALEMIC CARDIOPLEGIA()

Hyperkalemic cardioplegic solutions produce cardiac arrest during open heart surgery by depolarizing the sarcolemma, A recognized adverse ef fect of hyperkalemic cardioplegia is the possible development of ventr icular dysfunction believed to be related to intracellular Ca2+ loadin g, a consequence of K+-induced membrane depolarization. Adenosine has been proposed as an adjunct to hyperkalemic cardioplegic solutions. Ho wever, it is not known whether adenosine can affect K+-induced membran e depolarization, and associated intracellular Ca2+ loading. Perforate d patch-clamp method, applied to isolated single guinea-pig ventricula r myocytes, revealed that adenosine (1 mM) did not significantly reduc e the magnitude of K+-induced membrane depolarization (35.7 +/- 1.7 v 31.0 +/- 1.1 mV in the absence v presence of adenosine), Yet, adenosin e significantly slowed the rate of K+-induced membrane depolarization (167 +/- 32.8 v 67.9 +/- 12.9 mV/min in the absence v presence of aden osine) without directly affecting Ca2+, Na+, and K+ currents. Imposed ramp-pulses, with different rates (ranging from 0.33 to 0.05 V/s), but same magnitude of depolarization (100 mV), demonstrated that reductio n in the rate of membrane depolarization decreases net inward Ca2+ cur rent. Indeed, in Fluo-3 loaded ventricular myocytes, imaged by laser c onfocal microscopy, adenosine (1 mM) prevented K+- induced intracellul ar Ca2+ loading. The present findings indicate that adenosine slows th e rate of K+-induced membrane depolarization, and reduces K+-induced i ntracellular Ca2+ loading in ventricular myocytes. Such findings suppo rt the notion that adenosine may play a cardioprotective role in hyper kalemic cardioplegia. (C) 1996 Academic Press Limited