Endotoxemia-induced myocardial dysfunction is not associated with changes in myofilament Ca2+ responsiveness

1 Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, and 3 Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65211; and 2 Department of Physiology and Biophysics, University of Tennessee, Memphis, Tennessee 38163 Myocardial contractile function is depressed after onset of endotoxemia and is intrinsic to the ventricular myocyte. We tested the hypothesis that decreased Ca 2+ responsiveness of the contractile myofilaments underlies this inotropic depression. Specifically, we evaluated the relationship between Ca 2+ and unloaded cell shortening and isometric tension development of skinned guinea pig ventricular myocytes. Myocytes were isolated 4 h after intraperitoneal injection of 4 mg/kg Escherichia coli lipopolysaccharide (LPS) or saline (control; Ctl). Myofilament Ca 2+ responsiveness assessed by image analysis of shortening of skinned myocytes at pH 7.0 was not different between Ctl [pCa value that resulted in half-maximal shortening (pCa 50 ): 5.78 ± 0.04] and LPS (pCa 50 : 5.72 ± 0.02). Similarly, myofilament Ca 2+ responsiveness measured by isometric tension of skinned myocytes was not different between Ctl (pCa 50 : 5.73 ± 0.02) and LPS (pCa 50 : 5.76 ± 0.02). Maximal tension generated by LPS myocytes (2.89 ± 0.23 g/mm 2 ) was significantly less ( P