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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The decrease in the antithrombin III activity is thought to result from consumption by ongoing coagulation, degradation by neutrophil elastase, capillary leak syndrome, and impaired synthesis. A retrospective data analysis of patients with sepsis was conducted to investigate the response of antithrombin III activity after supplementation in patients with sepsis, and to determine what factors affect the response of antithrombin III activity. The study included 42 patients with sepsis, 75 patients with severe sepsis, and 65 patients with septic shock, who were administered antithrombin III. ⋯ The patients with liver dysfunction had significantly lower response to antithrombin III activity than that of the patients without liver dysfunction (P < 0.0001). A stepwise multiple linear regression analysis revealed that the severity of sepsis and liver function were independent predictors for the response to antithrombin III activity. These results suggest that the response to antithrombin III supplementation may be affected by both a systemic inflammation and impaired synthesis in patients with sepsis.
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To investigate the fluid tolerance of hemorrhagic shock with pulmonary edema (HSPE) at high altitude in unacclimated rats and the beneficial effect of 7.5% hypertonic saline/6% dextran (HSD). One hundred seventy-six Sprague-Dawley rats, transported to LaSa, Tibet, 3,760 m above the sea level, were anesthetized with sodium pentobarbital (30 mg/kg, i.p.) within 1 week. Hemorrhagic shock with pulmonary edema was induced by bloodletting (50 mmHg for 1 h) plus intravenous injection of oleic acid (50 microL/kg). ⋯ The tolerance of fluid infusion for hemorrhagic shock with pulmonary edema at high altitude is significantly decreased. More than one volume of LR infusion would aggravate the pulmonary edema and exacerbate the resuscitation effect, but only one volume of LR cannot reach the effective volume resuscitation. Small volume of HSD could better resuscitate hemorrhagic shock with pulmonary edema at high altitude.
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To examine the use of mechanical cardiac assist devices in prolonged hemorrhagic shock lasting up to 120 min. We induced hemorrhagic shock in anesthetized calves that were then treated 30 or 120 min later with either conventional fluid and blood resuscitation methods or the implantation of a mechanical assist device in addition to conventional fluid resuscitation. We measured hemodynamic and hematologic variables, inflammatory mediators, end-organ function via biochemical parameters, and survival time. ⋯ Furthermore, the biochemical profile, indicating liver and kidney function, and survival time were better after hemorrhage in device-treated calves than in conventionally treated calves. Levels of inflammatory mediators, which contribute to cell and organ dysfunction, were increased after hemorrhage, but calves with mechanical devices had less of an increase than did calves treated only with fluids. Our results indicate that the use of a mechanical cardiac assist device in combination with conventional fluid and blood resuscitation methods improves survival and end-organ recovery and decreases the myocardial inflammatory response after prolonged hemorrhagic shock when compared with the sole use of conventional fluid resuscitation techniques.
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Trauma/hemorrhagic shock (TH/S) has been associated with inflammation and immunodisorders, leading to immunosuppression, multiorgan dysfunction, and death. However, little is known about the effect of resuscitation with different solutions on the immunological function. To address this issue, groups of male Sprague-Dawley rats were induced with TH/S by fracture in the left femur and continual bleeding to keep the MAP of 30 +/- 5 mmHg for 30 min, followed by resuscitation with 6% hydroxyethyl starch solution (HES), Ringer's lactate solution (RS), or 5% albumin (ALB), and the impact of resuscitation on the activation, differentiation, and survival of CD4 T cells was longitudinally examined after TH/S and resuscitation. ⋯ Treatment with HES or ALB, but not RS, prevented CD4 T-cell apoptosis (sham, 7.23% +/- 3.4%; HES, 10.2% +/- 4.1%; RS, 15.2% +/- 5.4%; ALB, 10.6% +/- 4.3%; 48 h) and nuclear factor-kappaB p65 activation (sham, 0.17 +/- 0.04; HES, 0.34 +/- 0.05; RS, 0.41 +/- 0.09; ALB, 0.25 +/- 0.09; 48 h) induced by TH/S early after resuscitation. These data demonstrated that HES resuscitation modulated the balance of TH1 and TH2 responses and inhibited TH/S-related nuclear factor-kappaB activation and CD4 T-cell apoptosis in TH/S rats. Our findings provide new insights into understanding the TH/S-related immunodisorders and may aid in the design of new therapy for intervention of TH/S.
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Signaling through toll-like receptor 4 (TLR4) plays an obligate role in burn-related myocardial dysfunction. We hypothesized that signaling through CD14, a cellular receptor for endotoxin that lacks a transmembrane domain but is coupled to TLR4, also plays a role in postburn myocardial inflammation and dysfunction. Burn covering 40% total body surface area (or sham burn for controls) was produced in wild-type (WT) and CD14 knockout (KO) as well as vehicle-treated and geldanamycin-treated WT mice (1 microg/g body weight) to inhibit CD14 signaling. ⋯ Relative to sham WT controls, burn trauma in increased cardiac myocyte secretion of inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6 rose from 59 +/- 10 to 171 +/- 8; 6 +/- 0.2 to 78 +/- 1; and 88 +/- 3 to 170 +/- 12 pg/mL, respectively; P < 0.05) and produced robust cardiac contractile dysfunction (left ventricular pressure and +dP/dt fell from 105 +/- 4 to 73 +/- 5 mmHg and 2,400 +/- 73 to 1,803 +/- 90 mmHg/s; P < 0.05). Inability to signal through the CD14/TLR4 pathway (induced by CD14/KO or inhibition of CD14 expression by administration of geldanamycin) attenuated TNF-alpha, IL-1 beta, and IL-6 production in response to burn injury and improved postburn myocardial contractile function. Our data suggest that signaling through the CD14 pathway plays an obligate role in cardiac inflammation/dysfunction which occurs after major burn injury.