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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Systemic and microvascular hemodynamic responses to volume restoration from hemorrhagic shock were studied in the hamster window chamber model to determine the significance of blood rheological and oxygen transport properties. Moderated hemorrhage was induced by means of arterial controlled bleeding of 50% of the blood volume. The hypovolemic shock state was maintained for 1 h before resuscitation. ⋯ Oxygen delivery and extraction levels were significantly lower for resuscitation with plasma and MetHb-loaded RBCs compared with oxygen-carrying RBCs. The curtailed recovery of systemic and microvascular conditions after volume restitution with plasma seems to be due to the decrease in blood viscosity. Conversely, the restoration of blood rheological properties improves resuscitation independently of the restitution of oxygen-carrying capacity.
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We have demonstrated that volatile anesthetics reduce inflammation after renal ischemia/reperfusion injury in vivo. As hyperactive uncontrolled inflammation can lead to mortality and morbidity during early sepsis, we questioned whether the volatile anesthetic isoflurane could reduce mortality and protect against sepsis induced renal and hepatic dysfunction. Mice were anesthetized with isoflurane or with pentobarbital and subjected to cecal ligation and puncture (CLP) to induce septic peritonitis. ⋯ Isoflurane-treated mice had lower plasma levels of TNF-alpha, KC, and IL-6. Isoflurane-anesthetized mice also had significantly prolonged and increased survival compared with pentobarbital-anesthetized mice. Therefore, isoflurane anesthesia conferred significant protection against renal and hepatic dysfunction and death after septic peritonitis and attenuated renal inflammation and apoptosis compared with pentobarbital anesthesia.
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Nitric oxide (NO) prevents the myocardial apoptosis and dysfunction resulting from cardioplegia-induced cardiac arrest (CCA) under cardiopulmonary bypass (CPB). Inasmuch as CCA-induced myocardial dysfunction is associated with acute ischemia/reperfusion (I/R) and inflammatory response, which activates nuclear factor kappaB (NF-kappaB) translocation, we assessed the hypothesis that the detrimental effects of CCA under CPB result from NO imbalance inducing NF-kappaB activation. New Zealand white rabbits (10 in each group, each 2.5-3.5 kg) received total CPB. ⋯ The inflammatory and apoptotic responses of cardiomyocytes could be lessened by restoring NO concentration via modulation of the (1) nuclear translocation of NF-kappaB, (2) inducible NO synthase mRNA expression, (3) cytochrome c production, and (4) occurrence of apoptosis. Cardioplegia-induced cardiac arrest under CPB can decrease endogenous NO production, which can be restored with exogenous NO supplementation. Exogenous NO can ameliorate the myocardial inflammatory response by inhibition of NF-kappaB translocation, inflammatory gene expression, inducible NO synthase expression, and cytochrome c production.
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In recent investigations, high-mobility group box 1 (HMGB1) has been recognized to be an important factor in the development of sepsis. On the other hand, a serine protease inhibitor, nafamostat mesilate (NM) inhibits the enzyme activities of various protease and coagulation factors. We examined whether NM could inhibit HMGB1 in a rat sepsis model and thus could potentially be useful for treating sepsis. ⋯ Regarding the cell signal in each cell, we observed the inhibition of the phosphorylation of IkappaB. We thus concluded that it is possible to prevent the occurrence of pulmonary disorders in an endotoxic shock model by administering NM, however, this also inhibits the cell signal in a cell, mainly by the phosphorylation of IkappaB, thereby inhibiting the HMGB1 levels. Our findings thus suggest that the administration of NM may therefore potentially improve the condition of patients who have septic shock.
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Sepsis is one of the most important risk factors in acute respiratory distress syndrome (ARDS). beta-Glucan is a potent reticuloendothelial modulating agent, the immunobiological activity of which is mediated in part by an increase in the number and function of macrophages. In this study, we investigated the putative protective role of beta-glucan against sepsis-induced lung injury. Sepsis was induced by cecal ligation and puncture (CLP) in Wistar rats. ⋯ In contrast, beta-1,3-D-glucanase caused a significantly increased MPO and ICAM-1 levels in the lung. These data reveal that beta-glucan treatment improved the course of CLP-induced peritonitis and attenuated the lung injury. Administration of beta-glucanase inhibited the beta-glucan activity and resulted in enhanced lung injury.