ADENOSINE PREVENTS K-INDUCED CA2+ LOADING - INSIGHT INTO CARDIOPROTECTION DURING CARDIOPLEGIA()

In clinical practice, hyperkalemic cardioplegia induces sarcolemmic de polarization, and therefore is used to arrest the heart during open he art operations. However, the elevated concentration of K+ that is pres ent in cardioplegic solutions promotes intracellular Ca2+ loading, whi ch could aggravate ventricular dysfunction after cardiac operations. T his review highlights recent findings that have established, at the si ngle cell level, the protective action of adenosine against hyperkalem ia-induced Ca2+ loading. When it was added to hyperkalemic cardioplegi c solutions, adenosine, at millimolar concentrations and through a dir ect action on ventricular cardiomyocytes, prevented K+-induced Ca2+ lo ading. This action of adenosine required the activation of protein kin ase C, and it was effective only in cardiomyocytes with low diastolic Ca2+ levels. Of importance, adenosine did not diminish the magnitude o f K+-induced membrane depolarization, allowing unimpeded cardiac arres t. Taken together, these findings provide direct support for the idea that adenosine is valuable when used as an adjunct to hyperkalemic car dioplegia. This idea has emerged from previous clinical studies that h ave shown improvement of the clinical outcome after cardiac operations when adenosine or related substances were used to supplement cardiopl egic solutions. Further studies are required to define more precisely the mechanism of action of adenosine, and the conditions that may dete rmine the efficacy of adenosine as a cytoprotective supplement to card ioplegia. (C) by The Society of Thoracic Surgeons.