Cytosolic Ca2+ concentration and contraction-relaxation properties of ventricular myocytes from Escherichia coli endotoxemic guinea pigs: effect of fluid resuscitation.
Hearts isolated from a guinea pig model of Escherichia coli endotoxemia exhibit decreased systolic contractile function and reduced diastolic compliance of the left ventricle within 4 h after injection of endotoxin. Fluid resuscitation prevented the endotoxin-induced decrease in diastolic compliance without affecting systolic contractile depression. Because intrinsic myocardial dysfunction after endotoxemia may result from alterations in intracellular Ca2+ handling, we tested the hypothesis that in vivo fluid resuscitation improved diastolic function by altering Ca2+ handling of the myocardium. We tested this hypothesis by measuring cell shortening and intracellular Ca2+ of ventricular myocytes isolated from endotoxemic guinea pigs. E. coli endotoxin (LPS, 1 mg/kg)-injected guinea pigs were divided into resuscitated and nonresuscitated groups. Fluid resuscitated animals received a Ringer's infusion (8 mL.kg-1.h-1) intravenously (i.v.) beginning immediately after endotoxin injection. Four hours later, ventricular myocytes were isolated enzymatically and loaded with fura-2/AM. When myocytes were field stimulated at .8 Hz, peak systolic Ca2+ transients of LPS-resuscitated (619 +/- 75 nM) and LPS-nonresuscitated (599 +/- 60 nM) myocytes were not significantly different from each other, but both were significantly less than values from control myocytes (1187 +/- 118 nM, p < .05). The percentage of cell shortening of LPS-resuscitated (6.2 +/- .9%) and LPS-nonresuscitated (6.2 +/- .3%) myocytes were also less than control (11.8 +/- .5%, p < .05). In contrast to improved diastolic compliance of fluid-resuscitated hearts, diastolic [Ca2+]i of myocytes (at .8 Hz) from LPS-resuscitated animals (138 +/- 47 nM) was not statistically different from LPS-nonresuscitated animals (129 +/- 19 nM). Diastolic values of both LPS groups were consistently lower than control value (251 +/- 38 nM, p < .05). These data suggest that improved diastolic compliance of LPS hearts following fluid resuscitation is not associated with improved myocyte contractility or myoplasmic Ca2+ handling.
Zhong
J
J
Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia 65211, USA.
Adams
H R
HR
Rubin
L J
LJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D003600:Cytosol / Q000378:metabolism; D019446:Endotoxemia / Q000378:metabolism / Q000628:therapy*; D004926:Escherichia coli; D005440:Fluid Therapy; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology*; D016276:Ventricular Function
D008070:Lipopolysaccharides; D002118:Calcium