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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In rodents, inhaled H2S and injection of H2S donors protected against kidney ischemia/reperfusion (I/R) injury. During porcine aortic occlusion, the H2S donor Na2S (sulfide) reduced energy expenditure and decreased the noradrenaline requirements needed to maintain hemodynamic targets during early reperfusion. Therefore, we tested the hypothesis whether sulfide pretreatment may also ameliorate organ function in porcine aortic occlusion-induced kidney I/R injury. ⋯ While expression of heme oxygenase 1 and cleaved caspase 3 did not differ, sulfide reduced the expression Bcl-xL and increased the activation of nuclear transcription factor κB. During porcine aortic occlusion-induced kidney I/R injury, sulfide pretreatment attenuated tissue injury and organ dysfunction as a result of reduced inflammation and oxidative and nitrosative stress. The higher nuclear transcription factor κB activation was probably due to the drop in temperature.
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The intrathoracic pressure regulator (ITPR) (CirQLator; Advanced Circulatory Systems Inc, Roseville, Minn) is a novel, noninvasive device intended to increase cardiac output and blood pressure in hypovolemic or cardiogenic shock by generating a continuous low-level intrathoracic vacuum in between positive pressure ventilations. Although there are robust data supporting the benefit of the ITPR in multiple animal models of shock, the device has not been used in humans. The goals of this study were to evaluate both the safety and efficacy of the ITPR in humans. ⋯ There were no significant differences in systemic blood pressures, left ventricular volumes, stroke volume, or ejection fraction as measured by TEE. Using two different measurement techniques, application of the ITPR increased cardiac output in normovolemic anesthetized patients who underwent coronary artery bypass graft before sternotomy. These data suggest that the ITPR has the potential to safely and effectively increase cardiac output in humans.
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Systemic inflammatory response syndrome is associated with excessive production of nitric oxide (NO·) and superoxide (O2), forming peroxynitrite, which in turn, acts as a terminal mediator of cellular injury by producing cell necrosis and apoptosis. We examined the effect of the peroxynitrite decomposition catalyst, WW-85, in a sheep model of acute lung injury and septic shock. Eighteen sheep were operatively prepared and randomly allocated to the sham, control, or WW-85 group (n = 6 each). ⋯ Compared with injured but untreated controls, WW-85-treated animals had significantly improved gas exchange, reductions in airway obstruction, shunt formation, lung myeloperoxidase concentrations, lung malondialdehyde concentrations, lung 3-nitrotyrosine concentrations, and plasma nitrate-to-nitrite levels. Animals treated with WW-85 exhibited less microvascular leakage and improvements in pulmonary function. These results provide evidence that blockade of the nitric oxide-peroxynitrite pathway improves disturbances from septic shock, as demonstrated in a clinically relevant ovine experimental model.
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Liver injury/dysfunction developing in patients with sepsis may lead to an increased risk of death. Small-volume resuscitation with hyperoncotic albumin (HA) has been proposed to restore physiologic hemodynamics in hemorrhagic and septic shock. We evaluated whether HA resuscitation could alleviate the development of liver injury/dysfunction in rats with polymicrobial sepsis induced by cecal ligation and puncture (CLP). ⋯ The septic rats treated with HA had a higher survival when compared with those with 0.9% saline treatment. Moreover, the increased plasma IL-1β, plasma IL-6, plasma nitrite/nitrate concentrations, liver iNOS expression, and liver superoxide levels in CLP rats were attenuated after administration of HA. Thus, HA may be regarded as a potential therapeutic agent in the early treatment of septic shock to prevent or reduce subsequent liver failure.