Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Although the efficacy of colloid resuscitation fluids in restoring cardiovascular status in hemorrhagic shock is accepted, the effect they have on the activity of the reticuloendothelial system (RES) is less clear. As interaction with the RES may be important in determining susceptibility to infections after resuscitation the effects of three such fluids, hydroxyethyl starch, Haemaccel, and fresh autologous blood on RES function after a 40% hemorrhage have been investigated in BALB/C mice. The mice, anesthetized with isoflurane, were bled over a 10 min period, left hypovolemic for 30 min, and then resuscitated with their shed blood or the same volume of asanguineous fluid. ⋯ Lung uptake was not affected at any time with any fluid. The same volume of Haemaccel had no significant effect either on K or on organ uptake when given to normovolemic animals. The changes in organ uptake after hemorrhage and resuscitation with Haemaccel were partially prevented if animals were resuscitated with Haemaccel plus autologous red cells.
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Platelet-activating factor (PAF) is a potent vasoactive and inflammatory lipid mediator which has been implicated in the hemodynamic alterations of endotoxemia and sepsis. Different PAF receptor antagonists have been shown to attenuate the systemic and pulmonary disturbances of sepsis, but they were generally administered before the injection of endotoxin and their effects have not been consistent. To examine the effects of BB-882, a novel potent PAF receptor antagonist, on general hemodynamics and regional flow distribution in a canine endotoxic shock model, 14 anesthetized and ventilated dogs received 2 mg/kg of Escherichia coli endotoxin intravenously (i.v.) followed by generous fluid resuscitation. ⋯ This study demonstrates that the administration of a PAF receptor antagonist following endotoxic shock in fluid resuscitated dogs does not offer significant hemodynamic benefit. Pretreatment with BB-882 at the dose used only enhanced mesenteric perfusion. These findings do not support beneficial effects of PAF receptor antagonists in septic shock.
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Tumor necrosis factor-alpha (TNF) is a critical early mediator in the genesis of a systemic inflammatory response during a septic insult. Many of the harmful effects evident during sepsis are ascribed to excessive endogenous TNF production. Because the liver is an important source of circulating TNF during endotoxicosis, and because glucocorticoids are believed to have a regulatory role in suppressing endogenous TNF production, we evaluated the effect of adrenalectomy on the hepatic production of TNF in an isolated perfused liver model after cecal ligation and puncture (CLP) sepsis. ⋯ A separate mortality study was performed (N = 35) that demonstrated a CLP induced mortality of 45%, and a CLP/ADREX mortality of 100%. Thus, adrenalectomy increased circulating TNF and hepatic TNF production as well as mortality in CLP sepsis. These findings suggest an important role for endogenous glucocorticoids in modulating hepatic TNF production during CLP-induced sepsis.
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Sepsis is associated with altered blood rheology. Fluid infusion is an essential component of therapy for septic shock. The purpose of this study was to compare the rheologic changes associated with saline, albumin, and hydroxyethyl starch in sepsis. ⋯ These data indicate that hydroxyethyl starch increases blood viscosity, decreases erythrocyte deformability, and increases erythrocyte aggregation when compared with saline. These changes are less significant with albumin. In patients with sepsis, these effects may further compromise the already altered erythrocyte rheology.
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The interactions of polymorphonuclear leukocytes (PMN) and endothelial cells are modulated by adhesion molecules, inflammatory cytokines, and shear stress. We investigated the changes in PMN-endothelial cell interactions induced by interleukin (IL)-1 beta under low flow conditions. PMN were isolated from the venous blood of healthy adults, and endothelial cells were obtained from human umbilical veins. ⋯ In contrast, anti-ICAM-1 and anti-E-selectin mAb each reduced the number of PMN that migrated by reducing the number of PMN that adhered to the luminal surface without significantly influencing the percent of the adherent PMN that had migrated. Although anti-L-selectin mAb reduced the adherence and migration of PMN, these effects were not statistically significant. These results indicated that under low flow conditions, as well as in the nonflow state, PMN-endothelial cell interactions were elicited via CD11/CD18 and ICAM-1 without the involvement of selectins.