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

Myocardial contractile function is depressed after onset of endotoxemia and is intrinsic to the ventricular myocyte, We tested the hypothesis that: decreased Ca2+ responsiveness of the contractile myofilaments underlies this inotropic depression. Specifically, we evaluated the relationship between Ca2+ 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 Ca2+ 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 Ca2+ 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 < 0.05) than Ctl (3.75 +/- 0.34 g/mm(2)). However, when myocytes were isolated and skinned in the presence of protease inhibitors, maximal tension generated by LPS myocytes(3.53 +/- 0.98 g/mm(2)) was similar to Ctl (3.01 +/- 0.80 g/mm(2)). We conclude that in vivo administration of LPS resulting in Endotoxemia without shock does not alter myofilament Ca2+ responsiveness of ventricular myocytes. Rather, reduced contractility is more likely a result of decreased Ca2+ availability because systolic Ca2+ transients of fura 2-loaded LPS myocytes were significantly decreased (P ( 0.05) compared with Ctl myocytes.