Phosphorylation-dependent Alteration in Myofilament Ca2 + Sensitivity but Normal Mitochondrial Function in Septic Heart

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 (in 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 (pCa50, where pCa = − log10[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 dis...