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 both animal models of hemorrhagic shock and clinical settings, shock-induced gut ischemia has been implicated in the development of the systemic inflammatory response syndrome and distant organ injury, yet the factors transducing these events remain to be fully determined. Because hypoxia-inducible factor (HIF-1), a transcription factor composed of oxygen-labile HIF-1alpha and constitutive HIF-1beta subunits, regulates the physiologic/pathophysiologic response to hypoxia and ischemia, we examined the HIF-1 response in two rat models of gut ischemia-reperfusion. We found that ileal nuclear HIF-1alpha protein levels were induced in rats subjected to trauma (laparotomy) plus hemorrhagic shock for 90 min relative to their trauma sham-shock and naïve counterparts and that this trauma hemorrhagic shock-induced mucosal HIF-1alpha protein response persisted after 1 h and 3 h of reperfusion. ⋯ Furthermore, the addition of P. aeruginosa during either the hypoxic or reoxygenation phase prevented the degradation of HIF-1alpha protein levels. Moreover, the observation that lipopolysaccharide induced HIF-1alpha expression in a time-dependent manner in IEC-6 cells indicated that the induction of HIF-1 by exposure to P. aeruginosa is not dependent on bacterial viability. In conclusion, these results suggest that HIF-1alpha activation is an early reperfusion-independent event in models of gut ischemia-reperfusion and that this HIF-1alpha response is potentiated by the presence of P. aeruginosa or lipopolysaccharide.
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Local and systemic inflammation can lead to progression of burn wounds, converting second- to third-degree wounds or extending the burn to adjacent areas. Previous studies have suggested that the skin is an important site of production of nitric oxide (NO), synthesized by inducible nitric oxide synthase (iNOS) activation after injury. NO increases in burned wounds, but its formation in noninjured skin has not been investigated. ⋯ BBS-2 prevented the increase of NOx but not the increase of nitrotyrosine expression in skin. Plasma levels of NO increased in burned animals when compared with sham, but this increase was not significant. The increase of NO and its metabolites after burn in noninjured skin is followed by a significant increase in peroxynitrite, a potent cytotoxic mediator.