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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We examined the effects of hydroxyethyl starch (HES) on the microcirculation, hemodynamics, and colloidal osmotic pressure in a rabbit model of hemorrhagic shock. A total of 40 rabbits was anesthetized with pentobarbital and isoflurane, and they were mechanically ventilated. An ear chamber was prepared to examine blood vessels by intravital microscopy. ⋯ Recovery of arterial blood flow velocity and blood flow rate was also significantly better in the HES group than in the LR group (P < 0.005). Mean arteriolar pressure, central venous pressure, and plasma colloid osmotic pressure after the completion of infusion were significantly greater in the HES group than in the LR group (P < 0.005). We conclude that intravenous infusion of HES effectively maintains the microcirculation, hemodynamics, and colloidal osmotic pressure in a rabbit model of acute severe hemorrhage.
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We tested whether nitric oxide (NO) could synergize with hypoxia to induce damage to the aorta isolated from rat. We found that 4 h of mild hypoxia (5% O2) caused substantial necrosis of isolated rat aortae (measured as lactate dehydrogenase release) if inducible NO synthase (iNOS) had previously been induced by endotoxin plus interferon-gamma. Mild hypoxia caused no significant necrosis in the absence of this inflammatory activation, and inflammatory activation caused little damage at a higher oxygen levels (21% oxygen). ⋯ A specific inhibitor of mitochondrial respiration, myxothiazol, caused necrosis of aortae over a similar time course to NO. DETA/NO plus mild hypoxia-induced cell death was substantially reduced by a glycolytic intermediate 3-phosphoglycerate, suggesting that necrosis resulted from energy depletion secondary to respiratory inhibition. This NO-induced sensitization of aorta to mild hypoxia may be important in sepsis and other pathologies where iNOS is expressed.
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We investigated in rats the influence of the lymphatic system and of tumor necrosis factor (TNF) on the lung inflammation resulting from intestinal ischemia/reperfusion (I/R) performed by 45-min occlusion of the superior mesenteric artery followed by 2 h of reperfusion. A group of rats had the thoracic lymph duct ligated before I/R. In lungs, intestinal I/R evoked a significant neutrophil recruitment, and enhanced microvascular permeability, in addition to generation of TNF in serum. ⋯ Similarly, intestinal LDH activity and serum TNF levels were unaffected. Overall, our data show that the pulmonary and gut injuries induced by intestinal I/R are partially dependent on TNF, which is conceivably generated in the injured gut tissue due to intestinal I/R and carried by the lymphatic system. Thus, the mesenteric lymphatic drainage seems to play a role as a path modulator of the pulmonary and intestinal dysfunctions that follow a gut trauma.
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Na(+)/H(+) exchange (NHE) is involved in the myocardial injury that occurs during ischemia and reperfusion. The goal of the present study was to investigate the role of NHE in hypovolemic circulatory shock by using a potent NHE-1 selective inhibitor BIIB513. Acute rapid hemorrhage was induced in 14 pigs by bleeding (30 mL/kg over 30 min). ⋯ NHE blockade also attenuated the metabolic acidosis, improved tissue oxygen delivery, and improved cardiac function from resuscitation. The circulating levels of creatine phosphokinase (CPK) and cardiac troponin-I were significantly lower in the BIIB513 treatment group. These results suggest that NHE activation plays an important pathophysiological role in hypovolemic circulatory shock, and NHE-1 blockade is a powerful intervention to improve cardiovascular outcomes of resuscitation from prolonged hypovolemic circulatory shock.
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These studies evaluated the effects treatment with glucan phosphate, a soluble polysaccharide immunomodulator, on the inflammatory response induced by burn injury and on resistance to Pseudomonas aeruginosa burn wound infection. Mice were exposed to 35% total body surface area burns and were resuscitated with lactated Ringer's (LR) solution alone or LR supplemented with glucan phosphate (40 mg/kg). Glucan phosphate treatment attenuated burn-induced expression of interleukin (IL)-1beta, IL-6, and IL-10 mRNAs in spleen, lung, and heart. ⋯ Glucan phosphate treatment significantly improved survival in mice exposed to P. aeruginosa burn wound infection. The improved survival correlated with lower bacterial burden in the burn wound, attenuated production of proinflammatory cytokines, and enhanced production of Th1 cytokines. These studies show that glucan phosphate treatment attenuates burn-induced inflammation and increases resistance to P. aeruginosa burn wound infection in an experimental model of burn injury.