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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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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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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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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Acute injury produces an immediate activation of neuroendocrine mechanisms aimed at restoring hemodynamic and metabolic counter-regulatory responses. These counter-regulatory responses are mediated by the systemic and tissue-localized release of neuroendocrine-signaling molecules known to affect immune function. This has led to the recognition of the importance of neuroendocrine-immune modulation during acute injury as well as throughout the recovery period. ⋯ In turn, cells of the immune system and their products have been shown to influence peripheral and central neurotransmission, leading to the conceptualization of a bidirectional neuroimmune communication system. The reflex activation of this bidirectional neuroimmune pathway in response to injury, integrated with the parasympathetic nervous system, and opioid and glucocorticoid pathways responsible for orchestrating the counterregulatory stress response, results in dynamic regulation of host defense mechanisms vital for immune competence and tissue repair. This review provides the biological framework for the integration of our understanding of the neuroendocrine mechanisms involved in mediating the stress response and their role in modulating immune function during and after traumatic injury.