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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Hypotensive resuscitation has been advocated as a better means to perform field resuscitation of penetrating trauma. Our hypothesis is that hypotensive resuscitation using either crystalloid or colloid provides equivalent or improved metabolic function while reducing the overall fluid requirement for resuscitation of hemorrhage. We compared hypotensive and normotensive resuscitation of hemorrhage using lactated Ringer's (LR) with hypotensive resuscitation using Hextend (Hex), 6% hetastarch in isotonic buffered saline. ⋯ Mean minimum base excess (BE) values were +1.9 +/- 1.4, -5.8 +/- 4.3, and -5.9 +/- 4.0 mEq/L in the LR-90, LR-65, and Hex-65 treatments, respectively. Hypotensive resuscitation with LR greatly reduced volume requirements as compared with normotensive resuscitation, and Hex achieved additional volume sparing. However, trends toward lower BE values and the occurrence of deaths only in the hypotensive treatment protocols suggest that resuscitation to a target MAP of 65 mmHg may be too low for optimal outcomes.