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(Circulation Research. 2007;100:229.)
© 2007 American Heart Association, Inc.

Cellular Biology

Reduced Force Generating Capacity in Myocytes From Chronically Ischemic, Hibernating Myocardium

Virginie Bito^*, Jolanda van der Velden^*, Piet Claus, Christoph Dommke, Alfons Van Lommel, Luc Mortelmans, Erik Verbeken, Bart Bijnens, Ger Stienen, Karin R. Sipido

From the Division of Experimental Cardiology (V.B., K.R.S.), Division of Cardiac Imaging (P.C., C.D, B.B.), Laboratory of Pathology (A.V.L., E.V.), and Department of Nuclear Medicine (L.M), University Hospital Gasthuisberg and University of Leuven, Belgium; Laboratory for Physiology (J.v.d.V., G.S.), VU University Medical Center, Amsterdam, Netherlands.

Correspondence to Karin R. Sipido, MD, PhD, Division of Experimental Cardiology, KUL, Campus Gasthuisberg O/N 7th floor, Herestraat 49, B-3000 Leuven, Belgium. E-mail Karin.Sipido{at}med.kuleuven.ac.be

The contractile dysfunction of the hibernating myocardium in situ results from local environmental factors, but also from intrinsic cellular remodelling that may determine reversibility. Previous studies have suggested defects in myofilament Ca²⁺ responsiveness. We prepared single myocytes from control (CTRL, n_pigs=7) and from hibernating myocardium (HIB, n_pigs=8), removed the membranes and measured isometric force development during direct activation of the myofilaments. One- and 2-dimensional polyacrylamide gel electrophoresis and specific phosphoprotein immunoblotting were performed on tissue homogenates from matched samples. Cellular ultrastructure was evaluated using electron microscopy. Normalized for cross-sectional area, passive force was not different but maximal isometric force was significantly reduced in myocytes from HIB (11.6±1.5 kN/m² versus 18.7±1.6 kN/m² in CTRL, P<0.05). Ca²⁺ sensitivity and steepness of the normalized force-pCa relationship were not different, and neither was the rate of force redevelopment (K_tr). No alterations were observed in isoform expression, phosphorylation or degradation of specific myofibrillar proteins. However, in HIB samples the total protein volume density was decreased by 23% (P<0.05). Histology showed glycogen accumulation and electron microscopy confirmed a reduction in myofilament density from 69.9±1.9% in CTRL to 57.1±0.9% of cell volume in HIB (P<0.05). In conclusion, decreased potential for force development in the hibernating myocardium is related to a reduction of myofibrillar protein per cell volume unit with replacement by glycogen and mitochondria. These changes may contribute to slow functional recovery on revascularization.

Key Words: hibernation • contractile function • myocytes • calcium

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