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(Circulation. 1998;97:630-632.)
© 1998 American Heart Association, Inc.

Editorials

Do Alterations in Intercellular Coupling Play a Role in Cardiac Contractile Dysfunction?

Jeffrey E. Saffitz, MD, PhD; ; Kathryn A. Yamada, PhD

From the Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Mo.

Correspondence to Jeffrey E. Saffitz, MD, PhD, Department of Pathology, Box 8118, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110. E-mail saffitz@patholology.wustl.edu

Key Words: Editorials • myocardium • connexin43 • ischemia • proteins

Myocardial stunning¹ and hibernation² have been subjects of intense laboratory and clinical investigations to elucidate mechanisms responsible for contractile dysfunction after transient ischemia or chronic hypoperfusion. Considerable evidence has implicated the generation of oxygen-derived free radicals and derangements in myocardial energy metabolism and excitation-contraction coupling as major contributors to the pathogenesis of myocardial stunning and hibernation.^{3 4} Despite enormous progress in this area, however, our understanding of the cellular pathophysiology of contractile dysfunction in ischemic heart disease remains incomplete.

In this issue of Circulation, Kaprielian et al⁵ provide evidence for a novel mechanism involving alterations in intercellular coupling that might contribute to the pathogenesis of contractile dysfunction in hibernating myocardium. Using digital image processing techniques and confocal immunofluorescence microscopy, they measured the amount of the major cardiac gap junction protein connexin43 (Cx43) in left ventricular samples obtained from patients at the time of coronary artery bypass graft surgery. Biopsies were taken from well perfused, normally contracting wall segments (identified with preoperative thallium scans and magnetic resonance imaging studies) and from "reversibly ischemic" segments (showing improved thallium uptake on stress/redistribution images but no improvement in contractile function after revascularization) or "hibernating" segments (showing improved contractile performance in postoperative MRI studies). Mean gap junction area, determined by measuring the amount of Cx43 immunoreactive signal at intercellular junctions and expressed per unit of intercalated disk area, was reduced by 23% in reversibly ischemic segments and by 33% in hibernating tissue compared with normally perfused regions. The average size of an individual gap junction . . . [Full Text of this Article]

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