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J Thorac Cardiovasc Surg 1996;112:820-831
© 1996 Mosby, Inc.

CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

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

This study was supported by grants from the American Heart Association, the National Heart Foundation (Rockville, Md.), and the Pharmaceutical Research and Manufacturers of America Foundation (Washington, D.C.).

Received for publication July 5, 1995 Revisions requested Sept. 5, 1995; revisions received Dec. 5, 1995 Accepted for publication Jan. 26, 1996. Address for reprints: Andre Terzic, MD, PhD, Division of Cardiovascular Diseases, Guggenheim 7, Mayo Clinic, Rochester, MN 55905.

Abstract

Hyperkalemic solutions that are used as cardioplegic agents, while effective in inducing electromechanical arrest, are only partially cardioprotective, and ventricular dysfunction has been observed. The underlying 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 present in cardioplegic solutions. Yet no effective cytoprotective means against possible intracellular Ca²⁺loading, under these conditions, has been described. Recently, potassium channel openers, which open adenosine triphosphate–sensitive K⁺channels, have been reported to possess cardioprotective properties under global ischemic conditions. However, it is not known whether these novel agents could prevent intracellular Ca²⁺loading that could occur during cardioplegia. Intracellular Ca²⁺was monitored in ventricular myocytes, loaded with the Ca²⁺-sensitive fluorescent probe Fluo-3AM, using epifluorescent digital imaging and laser confocal microscopy. Exposure of a myocyte to a 16 mmol/L concentration of K⁺, a concentration of K⁺commonly used in cardioplegic solutions, induced a nonhomogeneous increase in intracellular Ca²⁺. Potassium channel opening drugs, such as aprikalim or nicorandil, effectively prevented these solutions from increasing intracellular Ca²⁺. The preventive effect of potassium channel opening drugs was antagonized by glyburide, a selective blocker 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 intracellular Ca²⁺loading, which can be prevented by potassium channel opening drugs. Therefore, potassium channel opening drugs should be considered to prevent intracellular Ca²⁺loading associated with the use of cardioplegic solutions. J THORACCARDIOVASCSURG1996;112:820-31

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