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Title
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Phosphorylation-dependent alteration in myofilament sensitivity but normal mitochondrial function in septic heart
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Author
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Abstract
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| The subcellular mechanisms responsible for myocardial depression during sepsis remain unclear. Recent data suggest a role for impaired energy generation and utilization, resulting in altered contractile function. Here, we studied the energetic and mechanical properties of skinned fibers isolated from rabbit ventricle in a nonlethal but hypotensive model of endotoxemia. Thirty-six hours after (lipopolysaccharide (LPS) injection tin the presence of altered myocardial contractility), mitochondrial respiration, coupling between oxidation and phosphorylation, and creatine kinase function were similar in preparations from endotoxemic: (LPS) and control animals. The maximal Ca2+-activated force was similar in LPS and control preparations. However, the Ca2+ concentration corresponding to half-maximal force (pCa(50) where pCa = -log(10)[Ca2+]) was 5.55 +/- 0.01 (n = 11) in LPS fibers versus 5.61 +/- 0.01 (n = 10) in control fibers (p < 0.01). Both protein kinase A (PKA) and alkaline phosphatase treatment led to the disappearance in the difference between control and LPS pCa(50) values. Incubation of control fibers with the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) did not change the Ca2+ sensitivity after subsequent skinning, whereas isoproterenol decreased pCa(50) from 5.62 +/- 0.01 to 5.55 +/- 0.01 (p < 0.01). These data suggest that during sepsis, cardiac mitochondrial and creatine kinase systems remain unaltered, whereas protein phosphorylation decreases myofibrillar Ca2+ sensitivity and may contribute to the depression of cardiac contractility. |
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Language
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English
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Source (journal)
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American journal of respiratory and critical care medicine. - New York, 1994, currens
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Publication
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New York
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2001
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ISSN
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1073-449X
[print]
1535-4970
[online]
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DOI
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10.1164/AJRCCM.163.2.2002128
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Volume/pages
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163
:2
(2001)
, p. 362-367
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ISI
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000167050900015
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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