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Am J Physiol Heart Circ Physiol 282: H821-H831, 2002. First published January 24, 2002; doi:10.1152/ajpheart.00471.2001
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Vol. 282, Issue 3, H821-H831, March 2002

Alteration of mitochondrial function in a model of chronic ischemia in vivo in rat heart

Sihem Boudina1, Muriel N. Laclau1, Liliane Tariosse1, Danièle Daret1, Gérard Gouverneur1, Simone Bonoron-Adèle1, Valdur A. Saks2, and Pierre Dos Santos1

1 Institut National de la Santé et de la Recherche Médicale U441, Athérosclérose and Institut Fédératif de Recherche 4, 33600 Pessac; 2 Laboratory of Bioenergetics, Université Joseph Fourier, Grenoble Cedex 9, France; and Laboratory of Bioenergetics, National Institute of Chemical and Biological Physics, 12618 Tallinn, Estonia

The aim of this study was to investigate mitochondrial alterations in an animal model of chronic myocardial ischemia in rats obtained by surgical constriction of the left coronary artery. Resting coronary blood flow was measured using the fluorescent microsphere technique. Contractile function, defined by rate-pressure product, and myocardial oxygen consumption were measured in a Langendorff preparation. The mitochondrial function was evaluated on permeabilized skinned fibers. Three weeks after surgery, ischemic hearts showed a significant decrease in coronary blood flow compared with sham. Hemodynamic measurements showed a significant systolic and diastolic dysfunction. Alterations in mitochondrial function in ischemic hearts were mainly characterized by a significant decrease in the maximal velocity and apparent half-saturation constant for ADP, loss of the stimulatory effect of creatine, and a stimulatory effect of exogenous cytochrome c. These functional alterations were supported by structural alterations characterized by mitochondrial clustering and swelling associated with membrane rupture. We conclude that the alterations in systolic function after chronic ischemia are supported by severe modifications of mitochondrial structure and function.

contractile function; energy metabolism; mitochondria


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