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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Editorial Review
Tumor necrosis factor in sepsis: mediator of multiple organ failure or essential part of host defense?
Tumor necrosis factor-alpha (TNF) exerts numerous influences which, in association with severe infection, subserve both detrimental as well as beneficial host responses. The current review addresses recent insights into the structure and function of this pleiotropic cytokine, with a particular emphasis upon cellular and organ system consequences of sepsis-induced TNF activity. A comparison of responses elicited by endotoxin or TNF administration are discussed as are mechanisms of endogenous TNF regulation, such as soluble receptors, anti-inflammatory cytokines, and counter-regulatory responses. A review of past and future clinical strategies for altering TNF activity during sepsis is also provided.
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The proper fluid resuscitation of hemorrhagic shock is still controversial. Hypertonic saline has been suggested for prehospital resuscitation of hemorrhagic shock, because of its superior ability to expand blood volume and elevate systemic blood pressure and cardiac output in a small volume and during a short time period. We have defined two types of hemorrhagic shock: controlled hemorrhagic shock (CHS), where the bleeding source is immediately occluded following hemorrhage, and uncontrolled hemorrhagic shock (UCHS), where bleeding is induced by injury to blood vessels that are left unoccluded. ⋯ A more favorable effect but still not statistically significant effect has been demonstrated in patients with a Glasgow Coma Scale of 8 or less. The efficacy of HS has not clearly been established in clinical trials, in all of which HS was used in combination with conventional crystalloid therapy. Further human trials are required to better define the patient population that would benefit most from the prehospital administration of HS.
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Tumor necrosis factor (TNF) plays a well known role during the development of multiple organ failure, in part due to its role for the expression of adhesion molecules on endothelial cells, thereby contributing to inflammatory reactions. The purpose of this study was to investigate the effects of TNF on leukocyte-endothelial interactions in the liver as a key organ during the systemic inflammatory response syndrome. In Sprague-Dawley rats (n = 6/group) hemorrhagic shock was induced by reduction of the mean arterial blood pressure (MAP) to 40 mmHg for 45 min; resuscitation was initiated by retransfusion of shed blood (60%) and Ringer's lactate. ⋯ Significant differences were observed particularly in respect to permanent adherent leukocytes with 31.8 +/- 4.7% in the shock/NaCl group and 20.7 +/- 2.6% (mean +/- S. E., p < .05) in the shock/TN3 group 5 h after resuscitation following hemorrhagic shock. Consistently higher adhesion rates were observed in the portal regions compared to pericentral regions of the liver lobules.(ABSTRACT TRUNCATED AT 250 WORDS)
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7.5% NaCl/6% dextran-70 (HSD) has been shown to be an effective, small volume resuscitation fluid following hemorrhage (HEM) in euhydrated (E) sheep. However, there is controversy whether hypertonic solutions would be effective in dehydrated (D) animals. Therefore, we used two groups (E and 4 days D) of chronically instrumented ewes to evaluate the responses to HSD following HEM. ⋯ HR increased further following HSD (E, 143 +/- 11; D, 158 +/- 5). PNa was raised 10 and 16 mEq/L in the E and D sheep, respectively, following HSD infusion, but no adverse effects associated with elevated PNa were observed in either group. Thus, HSD was effective in restoring MAP, CO, and TPR to baseline values in D sheep but it was at the expense of a lower SV and a higher HR than in E sheep.