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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During septic shock, muscle produces lactate by way of an exaggerated NaK-adenosine triphosphatase (ATPase)-stimulated aerobic glycolysis associated with epinephrine stimulation possibly through beta2 adrenoreceptor involvement. It therefore seems logical that a proportion of hyperlactatemia in low cardiac output states would be also related to this mechanism. Thus, in low-flow and normal-to-high-flow models of shock, we investigate (1) whether muscle produces lactate and (2) whether muscle lactate production is linked to beta2 adrenergic stimulation and Na+K+-ATPase. ⋯ Despite a decrease in blood flow, lactate formation was decreased by all the pharmacological agents studied irrespective of shock mechanism. This demonstrates that lactate production during shock states is related, at least in part, to increased NaK-ATPase activity under beta2 stimulation. In shock state associated with a reduced or maintained blood flow, an important proportion of muscle lactate release is regulated by a beta2 receptor stimulation and not secondary to a reduced oxygen availability.
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Thermal injuries greater than 20% body surface area (BSA) result in systemic shock with generalized edema in addition to local tissue destruction. Burn shock is induced by a variety of mediators, mainly immunomodulative cytokines. This experimental study evaluates if burn shock can be induced in healthy rats by transfer of burn plasma (BP) with mediators. ⋯ The burned tissue is no longer required for burn shock induction, and the pathophysiologic process seems to be self-perpetuating as early as 4 h posttrauma. Leukocytes are activated by thermal injury and BP infusion. The role of leukocyte-endothelium interactions for edema formation remains uncertain and requires further investigation.
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Prostacyclin prevents pulmonary vascular injury and shock by inhibiting increases in lung tissue levels of TNF in rats administered endotoxin. We previously reported that NO derived from eNOS increases endothelial production of prostacyclin. Because neutrophil elastase has been shown to decrease endothelial production of prostacyclin by inhibiting NOS activity, we examined whether neutrophil elastase inhibitors reduce pulmonary vascular injury and hypotension by inhibiting the decrease in pulmonary endothelial production of prostacyclin in rats administered endotoxin. ⋯ These inhibitors also reduced hypotension and inhibited increases in lung tissue levels of mRNA of the inducible form of NOS in animals administered endotoxin. The effects of neutrophil elastase inhibitors were completely reversed by pretreatment with nitro-L-arginine methyl ester, an inhibitor of NOS, or indomethacin, a nonspecific cyclooxygenase inhibitor. These observations suggested that neutrophil elastase might decrease the pulmonary endothelial production of prostacyclin by inhibiting endothelial NO production, thereby contributing to the development of pulmonary vascular injury and shock through increases in lung tissue levels of TNF in rats administered endotoxin.