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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HBOC-201, a bovine polymerized hemoglobin, has been proposed as a novel oxygen-carrying resuscitative fluid for patients with hemorrhagic shock (HS). Herein, we evaluated the hemostatic effects of HBOC-201 in an animal model of HS. A 40% blood loss-controlled hemorrhage and soft tissue injury were performed in 24 invasively monitored Yucatan mini-pigs. ⋯ Mild delayed effects on platelet and clot formation during the hospital phase are transient and likely related to fewer blood transfusions. In swine with HS, HBOC resuscitation induced less thrombopathy than HEX during the prehospital phase but more thrombopathy in the hospital phase. The delayed effects on platelet and clot formation during the hospital phase are transient and may be related to the need for fewer blood transfusions.
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Fluid resuscitation to maintain adequate tissue perfusion while reducing edema in the severely burned patient remains a challenge. Recent studies suggest that reactive oxygen species generated by thermal injury are involved in edema formation associated with burn. The present study tested the hypothesis that adding a free radical scavenger to the resuscitation fluid would reduce total fluid requirements in the treatment of severe thermal injury. ⋯ VC infusion also prevented the 4-fold increase in plasma thiobarbituric acid reactive substances seen in the LR group early after burn (P < 0.05). Tissue antioxidant status was similar between groups. In this sheep burn model, continuous high-dose VC infusion reduced net fluid balance, reduced indices of plasma lipid peroxidation, and maintained overall antioxidant status in comparison with standard-of-care LR treatment.
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Multisystem organ failure represents a major cause of mortality in intestinal ischemia and reperfusion (I/R), and oxidative stress plays a key role in its pathogenesis. Hypothermia is beneficial in I/R injury, but its effects on systemic oxidative stress have not been elucidated. The aim of this study was to evaluate the effects of moderate hypothermia on systemic oxidative stress after intestinal I/R injury. ⋯ Nitric oxide production was increased only in normothermic I/R animals. Moderate hypothermia attenuates systemic oxidative stress associated with experimental intestinal I/R in an animal model by decreasing lipid peroxidation in plasma, ileum, lungs, and kidneys, by preventing the depletion of gut glutathione, and by reducing systemic nitric oxide production. However, whether these effects persist after rewarming is unknown.
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This study was designed to determine the effects of different resuscitation fluids on the production of proinflammatory and anti-inflammatory cytokines in an animal model of hemorrhagic shock. Wistar male rats (n = 24; 8/group) were subjected to a volume-controlled hemorrhagic shock for 30 minutes and resuscitated as follows: (1) sham group without resuscitation, (2) lactated Ringer solution (LR), 3:1; (3) 4% hydroxyethyl starch (HES) solution, 1:1; and (4) 4% modified fluid gelatin (GEL), 1:1. Hemodynamic parameters were recorded, and blood samples were collected at 0 min and 30, 90, 150, 210, 270, and 330 min after hemorrhage for plasma levels of IL-6, IL-10, and TNFalpha. ⋯ LR, HES, and GEL are comparable in volume efficacy for resuscitation of hemorrhagic shock but are associated with different postresuscitation immune responses. Resuscitation with GEL may be associated with cytokine production favoring a proinflammatory response. The marked elevation of IL-6 observed in the GEL-treated animals may play a role in the relatively high frequency of anaphylactoid reaction in clinical use of GEL.
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A poorly controlled acute inflammatory response can lead to organ dysfunction and death. Severe systemic inflammation can be induced and perpetuated by diverse insults such as the administration of toxic bacterial products (e.g., endotoxin), traumatic injury, and hemorrhage. Here, we probe whether these varied shock states can be explained by a universal inflammatory system that is initiated through different means and, once initiated, follows a course specified by the cellular and molecular mechanisms of the immune and endocrine systems. ⋯ We found that a single model with different initiators including the autonomic system could describe the response to various insults. This model was able to predict a dose range of endotoxin at which mice would die despite having been calibrated only in nonlethal inflammatory paradigms. These results show that the complex biology of inflammation can be modeled and supports the hypothesis that shock states induced by a range of physiologic challenges could arise from a universal response that is differently initiated and modulated.