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J Thorac Cardiovasc Surg 2003;126:1265-1267
© 2003 The American Association for Thoracic Surgery

Editorials

Attenuation of postcardioplegia injury with inhibitors of the sodium-hydrogen exchanger

^a Section of Cardiothoracic Surgery, The Carlyle Fraser Heart Center, Emory University School of Medicine, Atlanta, Ga, USA
^b Department of Surgery, University of Kentucky, Lexington, Ky, USA

Received for publication May 31, 2003; revisions received June 9, 2003; revisions received June 18, 2003; accepted for publication June 25, 2003.

^* Address for reprints: Jakob Vinten-Johanson, PhD, Crawford Long Hospital of Emory University, Carlyle Fraser Heart Center, Cardiothoracic Research Laboratory, 550 Peachtree St NE, Atlanta, Ga 30308-2225, USA
jvinten@emory.edu

The first 300 words of the full text of this article appear below.

See related article on page 1442.

 

There is increasing evidence that the myocardial necrosis that occurs during coronary artery bypass grafting (CABG) surgery is due to, in part, inadequate myocardial protection and that one of the underlying mechanisms is related to activation of the sodium-hydrogen exchanger (NHE). The NHE is one of 2 intracellular alkalinizing exchangers in mammalian cells; the second mechanism is the Na-HCO₃ exchanger. To date, 7 different isoforms of the NHE have been identified and are termed NHE-1 through NHE-7. NHE-1 is the primary isoform in mammalian myocardium. It is a 110-kd glycosylated protein localized in the sarcolemmal membrane of the cardiomyocyte. Its activity is regulated, in part, by a proton sensor on the cytosolic surface of the exchanger that is sensitive to intracellular H⁺ concentration ([H⁺]_i). In the resting state the NHE-1 is relatively quiescent, but during ischemia, increased intracellular accumulation of H⁺ stimulates the proton sensor, and activity of the exchanger is, in turn, increased by allosteric modifications of the molecule. The NHE-1 is also stimulated by other exogenous stimuli, such as cytokines, endothelin 1 (ET-1), thrombin, -adrenergic agents, and byproducts of ischemic metabolism, such as hydrogen peroxide and lysophosphatidylcholine.

NHE-1 activity has been implicated as a mechanism underlying both myocardial and endothelial cell dysfunction caused by ischemia-reperfusion injury.¹ During ischemia, the associated increase in [H⁺]_i caused by anaerobic metabolism stimulates the NHE-1, which leads to a concomitant increase in intracellular Na⁺ concentration ([Na⁺]_i). Extrusion of Na⁺ ions is limited, however, by the inhibition of the Na⁺-K⁺ adenosine triphosphatase pump that occurs as a result of ischemia-induced depletion of adenosine triphosphate. The increased [Na⁺]_i slows or reverses the direction of the Na⁺/Ca²⁺ exchanger, which normally extrudes Ca²⁺ in exchange for Na⁺ when operating in the forward direction. . . . [Full Text of this Article]