POTASSIUM CHANNEL OPENERS PREVENT POTASSIUM-INDUCED CALCIUM LOADING OF CARDIAC-CELLS - POSSIBLE IMPLICATIONS IN CARDIOPLEGIA

Hyperkalemic solutions that are used as cardioplegic agents, while eff ective in inducing electromechanical arrest, are only partially cardio protective, and ventricular dysfunction has been observed, The underly ing pathophysiology of cardioplegia-associated ventricular dysfunction is complex and not fully understood, but it could be related, in part , to intracellular Ca2+ loading induced by high K+ concentrations pres ent in cardioplegic solutions, Yet no effective cytoprotective means a gainst possible intracellular Ca2+ loading, under these conditions, ha s been described, Recently, potassium channel openers, which open aden osine triphosphate-sensitive K+ channels, have been reported to posses s cardioprotective properties under global ischemic conditions, Howeve r, it is not known whether these novel agents could prevent intracellu lar Ca2+ loading that could occur during cardioplegia, Intracellular C a2+ was monitored in ventricular myocytes, loaded with the Ca2+-sensit ive fluorescent probe Fluo-3AM, using epifluorescent digital imaging a nd laser confocal microscopy, Exposure of a myocyte to a 16 mmol/L con centration of RC, a concentration of K+ commonly used in cardioplegic solutions, induced a nonhomogeneous increase in intracellular Ca2+, Po tassium channel opening drugs, such as aprikalim or nicorandil, effect ively prevented these solutions from increasing intracellular Ca2+. Th e preventive effect of potassium channel opening drugs was antagonized by glyburide, a selective,locker of adenosine triphosphate-sensitive K+ channels. This study demonstrates, at the single cardiac cell level , that solutions containing a 16 mmol/L concentration of K+ promote in tracellular Ca2+ loading, which can be prevented be potassium channel opening drugs, Therefore, potassium channel opening drugs should be co nsidered to prevent intracellular Ca2+ loading associated with the use of cardioplegic solutions.