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 tested if vagus nerve stimulation (VNS) would prevent gut injury, mesenteric lymph toxicity, and systemic multiple organ dysfunction syndrome following trauma-hemorrhagic shock (T/HS). Four groups of experiments were performed. The first tested whether VNS (5 V for 10 min) would protect against T/HS-induced increases in gut and lung permeability as well as neutrophil priming. ⋯ Similar to VNS, the administration of nicotine also protected the gut from injury after T/HS. Vagus nerve stimulation prevents T/HS-induced gut injury, lung injury, neutrophil priming, and the production of biologically active mesenteric lymph. This protective effect of VNS was not dependent on the spleen but appeared to involve a cholinergic nicotinic receptor, because its beneficial effects could be replicated with nicotine.
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Severe crush injury is associated with high mortality because of resulting hyperkalemia in early phase and multiorgan dysfunction in later phase. In this study, we investigated the effects of sivelestat administration 1 h before reperfusion on the outcome of crush injury. Crush injury was induced by 6 h of direct compression to both hindlimbs of anesthetized rats with blocks weighing 3.5 kg each side, followed by 3 h of reperfusion. ⋯ Treatment with sivelestat significantly improved survival rate with P = 0.032. This was accompanied by lower serum high-mobility group box 1 (HMGB1) levels after 3-h reperfusion, attenuated lung injury (assessed using hematoxylin-eosin stain), and suppression of HMGB1 expression in the lung and the liver. These results suggest that treatment with sivelestat improves the outcome of crush injury, likely by inhibiting HMGB1 in rats.
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In this study, experiments were designed to determine whether microRNAs (miRNAs) play a role in the regulation or modulation of cardiomyocytic reactions under cardioplegia-induced cardiac arrest during cardiopulmonary bypass. MicroRNAs play powerful and unexpected roles in numerous cardiovascular diseases. MicroRNA-based therapeutics may provide a unique opportunity to translate this knowledge into the clinical setting. ⋯ Transfection of H9c2 cardiomyocytes with pre-miRNA-27a, which significantly decreased the mRNA and protein levels of interleukin 10 and increased expression of nuclear factor κB and its downstream cytokines during hypoxia/reperfusion injury, could activate caspase 3 and apoptosis. Our study demonstrated the altered expression of miRNAs in cardiomyocytes during cardioplegia-induced cardiac arrest. The involvement of miRNAs in cardiomyocytic apoptosis adds another level of complexity to gene regulation, which could open up novel avenues for cardiac protection strategies during cardiac surgery.