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Cardiac contractile impairment associated with increased phosphorylation of troponin I in endotoxemic rats
Author(s) -
Tavernier Benoît,
Li JianMei,
ElOmar Magdi M.,
La Sophie,
Yang ZhaoKang,
Trayer Ian P,
Mebazaa Alexandre,
Shah Ajay M.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0433fje
Subject(s) - myofilament , medicine , troponin i , nitric oxide , intracellular , endocrinology , phosphorylation , myocyte , lipopolysaccharide , troponin , sepsis , cardiac function curve , chemistry , heart failure , biochemistry , myocardial infarction
The subcellular mechanisms underlying intrinsic myocardial depression during sepsis remain poorly defined, in particular the relative roles of altered intracellular Ca 2+ transients versus changes in myofilament properties. We studied contractile function of cardiac myocytes isolated 12 h after induction of endotoxemia (5 mg/kg intravenous E. coli lipopolysaccharide [LPS]) in conscious rats. Cardiomyocytes from LPS‐injected rats had depressed twitch shortening compared with control cells (4.1±0.2% versus 7.8±0.3%; P<0.001; 0.5‐Hz stimulation), but similar Ca 2+ transients (peak indo‐1 ratio 1.13±0.02 versus 1.12±0.02; P = NS). Contractile depression was unaffected by inhibitors of nitric oxide synthase. Steady‐state myofilament response to Ca 2+ , assessed by tetanization of intact cells over a range of [Ca 2+ ], was reduced significantly in the LPS group ( P <0.001). Intracellular pH (SNARF fluorescence) was similar in both groups, but the amount of phosphorylated troponin I present in endotoxemic myocardium was approximatel 2 y + twofold greater than in control myocardium. In addition, steady‐state myofilament response to Ca 2+ was unaffected by isoproterenol (3 nmol/L) in endotoxemic cells, whereas there was a rightward shift in control cells. A reduction in myofilament response to Ca 2+ is the major determinant of intrinsic cardiac depression in systemic endotoxemia. This condition appears to be related to an increase in myocardial troponin I phosphorylation.