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 (pCa50): 5.78 +/- 0.04] and LPS (pCa50: 5.72 +/- 0.02). Similarly, myofilament Ca2+ responsiveness measured by isometric tension of skinned myocytes was not different between Ctl (pCa50: 5.73 +/- 0.02) and LPS (pCa50: 5.76 +/- 0.02). Maximal tension generated by LPS myocytes (2.89 +/- 0.23 g/mm2) was significantly less (P < 0.05) than Ctl (3.75 +/- 0.34 g/mm2). However, when myocytes were isolated and skinned in the presence of protease inhibitors, maximal tension generated by LPS myocytes (3.53 +/- 0.98 g/mm2) was similar to Ctl (3.01 +/- 0.80 g/mm2). 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.
Rigby
S L
SL
Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia 65211, USA.
Hofmann
P A
PA
Zhong
J
J
Adams
H R
HR
Rubin
L J
LJ
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004558:Electric Stimulation; D019446:Endotoxemia / Q000473:pathology / Q000503:physiopathology*; D004926:Escherichia coli; D005456:Fluorescent Dyes; D016257:Fura-2; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology; D012518:Sarcomeres / Q000473:pathology
D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D011480:Protease Inhibitors; D002118:Calcium; D016257:Fura-2