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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The return of heparinized shed blood (SB) in trauma/hemorrhagic shock (T/HS) models remains controversial because of potential anti-inflammatory properties. Although ubiquitous as an anticoagulant, heparin is ineffective on cellular coagulation as an antithrombotic agent. Therefore, we hypothesized that returning heparinized SB would paradoxically enhance acute lung injury (ALI) after T/HS because of the infusion of activated platelets. ⋯ Animals with return of SB had increased pulmonary polymorphonuclear leukocyte sequestration (P < 0.0001). Pulmonary immunofluorescence demonstrated microthrombi only in the T/HS group receiving heparinized SB (P < 0.0001). The return of heparinized SB functions as a "second hit" to enhance ALI, with activated platelets propagating microthrombi and pulmonary polymorphonuclear leukocyte recruitment.
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Hemorrhage is responsible for up to 40% of trauma mortality, and of these deaths, 33% to 56% occur during the prehospital period. In an effort to translate the cardioprotective effects of Adenocaine (adenosine, lidocaine) and Mg (ALM) from cardiac surgery to resuscitation science, we examined the early resuscitative effects of 7.5% NaCl with ALM in the rat model of 60% blood loss. Male Sprague-Dawley rats (250-350 g, n = 40) were anesthetized and randomly assigned to one of five groups: (a) untreated, (b) 7.5% NaCl, (c) 7.5% NaCl/6% dextran 70, (d) 7.5% NaCl/Mg, and (e) 7.5% NaCl/ALM. ⋯ At the end of phase 1, MAP of 7.5% NaCl/ALM-treated animals increased from 29 to 40 mmHg (P < 0.05). At the end of phase 2, MAP, PP, HR, and rate-pressure product in the ALM group were 75%, 193%, 96%, and 83% of their preshock values. Small-volume (∼1 mL/kg) i.v. bolus of 7.5% NaCl/ALM led to 100% survival following 60% blood loss with higher MAP than any group, an 89% to 96% reduction in the total number of arrhythmias, and a stable HR.
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High-mobility group box 1 (HMGB1) is a nuclear factor and a secreted protein. During inflammation, HMGB1 is secreted into the extracellular space where it can interact with the receptor for advanced glycation end products and trigger proinflammatory signals. Extracellular HMGB1 plays a critical role in several inflammatory diseases such as sepsis and rheumatoid arthritis. ⋯ The MEK1/2 inhibitor PD98059 also suppressed HMGB1 release and activation of nuclear factor κB induced by VPA. Valproic acid induced expression of γ-aminobutyric acid receptors in macrophages, and picrotoxin, a γ-aminobutyric acid A receptor antagonist, inhibited the VPA-activated phosphorylation of ERK and VPA-induced HMGB1 release. These results suggest that VPA may exacerbate innate immune responses to endotoxin through enhanced release of HMGB1.