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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Both fluid management and renal replacement therapies play a fundamental role in the treatment of critically ill patients. In a recent in vitro study, we have shown specific interactions of different colloids and the hemocompatibility of hemofilters. The present study was performed to compare the five most common fluids for volume resuscitation, i.e., normal saline (SAL), hydroxyethyl starch 130 kd/0.4 (HES130), hydroxyethyl starch 200 kd/0.5 (HES200), albumin (ALB), and gelatin (GEL) with respect to their interaction with continuous venovenous hemofiltration (CVVH) in anesthetized domestic pigs. ⋯ Direct in vivo effects of colloids in anaesthetized and ventilated pigs are not predictable for their effects during CVVH. Interaction between CVVH and every volume substitute occur in a highly specific manner. This observation could be helpful to explain contradictory study results and should be considered for future study designs.
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Ninety percent of patients with minor head injury (MHI) who have cranial computed tomography (CCT) under the present clinical decision rules have normal scans. Serum concentrations of the astroglial protein S-100B were recently found to provide useful information, but these studies were too small to provide a statistically safe basis for changing the present rule. We have investigated whether S-100B concentrations in patients with MHI can provide additional information to improve indication of the need for an initial CCT scan. ⋯ With a cutoff limit of 0.10-microg/L S-100B (95th percentile of values in healthy volunteers), CCT+ patients were identified with a sensitivity level of 99% (95% confidence interval, 96% - 100%) and a specificity level of 30% (95% confidence interval, 29% - 31%). Adding the measurement of S-100B concentration to the clinical decision rules for a CCT scan in patients with MHI could allow a 30% reduction in scans. A prospective study of the clinical value of S-100B measurement in such patients is now under way.
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Glycogen synthase kinase 3beta (GSK-3beta) is a serine/threonine protein kinase that has recently emerged as a key regulatory switch in the modulation of the inflammatory response. Dysregulation of GSK-3beta has been implicated in the pathogenesis of several diseases including sepsis. Here we investigate the effects of 2 chemically distinct inhibitors of GSK-3beta, TDZD-8 and SB216763, on the circulatory failure and the organ injury and dysfunction associated with hemorrhagic shock. ⋯ In addition, TDZD-8, but not SB216763, attenuated the increase caused by hemorrhage and resuscitation in plasma levels of the proinflammatory cytokine interleukin 6 and also of the anti-inflammatory cytokine interleukin 10. Neither of the GSK-3beta inhibitors however affected the delayed fall in blood pressure caused by hemorrhagic shock. Thus, we propose that inhibition of GSK-3beta may represent a novel therapeutic approach in the therapy of hemorrhagic shock.
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Excessive NO has been shown to play a major role in the pathogenesis of multiple organ dysfunctions in septic condition. Burn injury, especially if it is associated with smoke inhalation, is often complicated by subsequent development of pneumonia or sepsis that determine the outcome. In the present study, we developed an ovine sepsis model, created by exposing sheep to smoke inhalation followed by instillation of bacteria into the airway, that closely mimics human sepsis and pneumonia. ⋯ The hypotension seen in nontreated animals was not ameliorated either. The increase in plasma concentration of nitrate and nitrite was inhibited by BBS-2. The results of present study show that iNOS may be partially involved in the pathogenesis of acute lung injury induced by smoke inhalation followed by bacterial instillation in the airway.
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Administration of a single bolus of endotoxin is a model of sepsis response in experimental animal studies. Large animal species, such as pigs and sheep, are more sensitive to endotoxin administration due to an initial excessive pulmonary hypertensive response frequently resulting in acute right heart dysfunction. We investigated whether infusion of high-dose endotoxin in pigs but administered in an increasing dose results in inflammatory response without excessive pulmonary hypertension and right heart dysfunction. ⋯ In contrast, plasma levels of nitrite/nitrate, IL-1ra (as marker of cytokine response), remained markedly increased at 5 h after endotoxin infusion as compared with baseline values. Plasma markers of organ damage were significantly increased. Our data show that the dosing of endotoxin in an increasing manner in pigs produces a reliable model of an experimental sepsis response and organ dysfunction without immediate overwhelming pulmonary hypertension resulting in cardiovascular failure.