Cardiac contractile impairment associated with increased phosphorylation of troponin I in endotoxemic rats

SPECIFIC AIMSThisstudy aims to investigate the subcellular mechanisms responsible for intrinsic cardiac myocyte dysfunction in systemic sepsis in vivo, in particular the relative contribution of alterations in cytosolic Ca2+ homeostasis versus changes in myofilament responsiveness to Ca2+. We studied contractile function, intracellular Ca2+, intracellular pH, and myofilament properties in ventricular cardiac myocytes isolated from rats that had been subjected to lipopolysaccharide (LPS)-induced systemic sepsis in the conscious state.PRINCIPAL FINDINGS1. Reduced twitch contraction of myocytes from LPS-treated rats is attributable primarily to alteration in myofilament propertiesMyocytes were isolated from rats 12 h after LPS (or saline) injection, at which stage LPS-treated animals manifested pyrexia, modest weight loss, and hypotension. Cell shortening was significantly lower in LPS compared with control cells (4.1±0.2% versus 7.8±0.3% ; P<0.001 ; 0.5 Hz), whereas peak [Ca2+]i was similar (indo-1 fluoresc...