Cardiac contractile impairment associated with increased phosphorylation of troponin I in endotoxemic rats.
The subcellular mechanisms underlying intrinsic myocardial depression during sepsis remain poorly defined, in particular the relative roles of altered intracellular Ca2+ 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 (4.10.2% versus 7.80.3%; P2+ transients (peak indo-1 ratio 1.130.02 versus 1.120.02; P = NS). Contractile depression was unaffected by inhibitors of nitric oxide synthase. Steady-state myofilament response to Ca2+, assessed by tetanization of intact cells over a range of [Ca2+], was reduced significantly in the LPS group (P2+ 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 Ca2+ 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.
Tavernier
B
B
Department of Cardiology, Guy's King's and St. Thomas's School of Medicine, King's College London, UK.
Li
J M
JM
El-Omar
M M
MM
Lanone
S
S
Yang
Z K
ZK
Trayer
I P
IP
Mebazaa
A
A
Shah
A M
AM
D008841:Actin Cytoskeleton / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D019446:Endotoxemia / Q000378:metabolism / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006352:Heart Ventricles; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D019210:Troponin I / Q000378:metabolism*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D008070:Lipopolysaccharides; D019210:Troponin I; D019323:omega-N-Methylarginine; D007545:Isoproterenol; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester