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(Circulation. 2004;110:3313-3321.)
© 2004 American Heart Association, Inc.

Heart Failure

Temporal and Spatial Variations in Structural Protein Expression During the Progression From Stunned to Hibernating Myocardium

V.L.J.L. Thijssen, PhD; M. Borgers, PhD; M.-H. Lenders, BSc; F.C.S. Ramaekers, PhD; G. Suzuki, MD, PhD; B. Palka, BS; J.A. Fallavollita, MD; S.A. Thomas, PhD; J.M. Canty, Jr, MD

From the Department of Molecular Cell Biology, Cardiovascular Research Institute Maastricht, University of Maastricht, the Netherlands (V.L.J.L.T., M.B., M.-H.L., F.C.S.R.), and the Veterans Affairs Western New York Health Care System and Departments of Medicine, Physiology + Biophysics, State University of New York at Buffalo (G.S., B.P., J.A.F., S.A.T., J.M.C.).

Correspondence to Victor L.J.L. Thijssen, PhD, Department of Pathology, Academic Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. E-mail v.thijssen{at}path.unimaas.nl

Received October 2, 2003; de novo received May 10, 2004; revision received June 29, 2004; accepted June 30, 2004.

Background— Dysfunctional and normally perfused remote regions show equal myolysis and glycogen accumulation in pig hibernating myocardium. We tested the hypothesis that these arose secondary to elevations in preload rather than ischemia.

Methods and Results— Expression of structural protein (desmin, desmoplakin, titin, cardiotin, -smooth muscle actin, lamin-A/C, and lamin-B2) in viable dysfunctional myocardium was analyzed by immunohistochemistry. We performed blinded analysis of paired dysfunctional left anterior descending coronary artery and normal remote subendocardial samples from stunned (24 hours; n=6), and hibernating (2 weeks; n=6) myocardium versus sham controls pigs (n=7). Within 24 hours, cardiac myocytes globally reexpressed -smooth muscle actin. In stunned myocardium, cardiotin was globally reduced, whereas reductions in desmin were restricted to the dysfunctional region. Alterations progressed with the transition to hibernating myocardium, in which desmin, cardiotin, and titin were globally reduced. A qualitatively similar reorganization of cytoskeletal proteins occurred 3 hours after transient elevation of left ventricular end-diastolic pressure to 33±3 mm Hg.

Conclusions— Qualitative cardiomyocyte remodeling similar to that in humans with chronic hibernation occurs rapidly after a critical coronary stenosis is applied, as well as after transient elevations in left ventricular end-diastolic pressure in the absence of ischemia. Thus, reorganization of cytoskeletal proteins in patients with viable dysfunctional myocardium appears to reflect chronic and/or cyclical elevations in preload associated with episodes of spontaneous regional ischemia.

Key Words: stunning, myocardial • hibernation • proteins • structure • ischemia

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