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 pyruvate dehydrogenase (PDH) complex undergoes reversible phosphorylation catalyzed by a PDH kinase (inactivating) and a PDH phosphatase (activating). In skeletal muscle, a decreased proportion of PDH complex in the active, nonphosphorylated form (PDHa) limits glucose oxidation and promotes the conversion of pyruvate to lactate. Increased lactate formation with the accompanying hyperlactatemia is a frequent metabolic complication of sepsis. ⋯ Furthermore, the PDH kinase activity was decreased to values observed in control values. The results are consistent with the hypothesis that a reduced PDHa in skeletal muscle during sepsis is responsible, in part, for the hyperlactatemia characteristic of septic hypermetabolism. Furthermore, the results provide evidence that the decrease in PDHa results from a stable stimulation of PDH kinase activity.
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Randomized Controlled Trial Clinical Trial
Effects of supplemental dietary arginine, canola oil, and trace elements on cellular immune function in critically injured patients.
Dietary nutrients may have pharmacological value in modulating the immune system. We studied the effects of two enteral diets, which differed in their content of arginine, fat source, and select trace elements, on immune function in critically injured patients. Leukocytes were isolated from healthy volunteers and severely injured (ISS > 13) patients on the first, sixth, and tenth day of receiving either a standard diet or experimental diet. ⋯ Leukocyte function was uniformly depressed compared to normal patients on day 1. The response of leukocytes from patients receiving experimental diet improved or "normalized" by day 6, while remaining depressed in patients receiving standard diet. Dietary nutrient modification can effect cellular immune responses to inflammatory stimuli in severely injured patients.
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The time course of gastric intramucosal pH (pHi) during the early phase of resuscitation of hemorrhagic shock has not been adequately characterized. We examined pHi using gastric tonometry catheters in an anesthetized dog model of hemorrhagic shock. Shock was induced in 10 animals to maintain mean arterial blood pressure (MAP) at 40-45 mmHg for 30 min, followed by transfusion of shed blood plus additional saline as needed to maintain MAP at pre-shock values. ⋯ MAP, heart rate, and pHi did not change significantly during the experiment in the control group. These results indicate that prompt and adequate MAP response to resuscitation failed to prevent significant decreases of pHi in the first few hours post-resuscitation. This finding may be related to persistent splanchnic hypoperfusion or reperfusion injury.
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Intravenous administration of LPS to rats results in the accumulation of both neutrophils and platelets in the liver and the development of midzonal hepatocellular necrosis. The development of liver injury entails contributions from both cellular and soluble mediators, including neutrophils, platelets, Kupffer cells, tumor necrosis factor-alpha (TNF-alpha), and components of the coagulation system. Much remains unknown about the interactions among these mediators in the pathogenesis of liver injury in vivo. ⋯ Pretreatment with GdCl3 attenuated LPS-induced thrombocytopenia and hepatic platelet accumulation, as measured by radiolabeled platelets. Treatment with GdCl3 did not, however, alter the elevation in plasma TNF-alpha activity or the activation of the coagulation system, as evidenced by a decreased in plasma fibrinogen concentration. These results suggest that Kupffer cells contribute to LPS-induced hepatic platelet accumulation and raise the possibility that protection against LPS-induced hepatic injury by Kupffer cell inactivation may be due at least partly to decreased deposition of platelets within the liver.
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Isolated third-order pulmonary arteries and veins from sheep were examined for the effects of septicemia on norepinephrine-induced contractions, nitric oxide (NO)-mediated dilation, and basal cyclic GMP levels. The groups studied were as follows: control sheep (n = 7); sheep given live Pseudomonas aeruginosa (Ps, n = 6) for 48 h; and sheep given NG-mono-methyl-L-arginine during the last 24 h of Ps infusion (Ps-L-NMMA, n = 4). The norepinephrine-induced contractions were significantly greater (p < .05) in arteries from septic (Ps and Ps-L-NMMA) sheep. ⋯ Removal of endothelium enhanced contractions and decreased cyclic GMP in arteries and veins only from control sheep. The results show that septicemia differently affects the pulmonary artery and vein. The enhanced vasoconstriction of the artery is due to decreased endothelium-dependent NO release; the attenuated vasoconstriction of the vein is associated with NO-mediated increased cyclic GMP levels.