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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Comparative Study
Prevention of systemic hyperlactatemia during splanchnic ischemia.
Arterial blood lactate increases as a result of poor tissue perfusion. In splanchnic hypoperfusion, increased hepatic lactate uptake may delay increases in arterial blood lactate. We hypothesized that during isolated reduction of mesenteric blood flow, maintaining systemic blood volume and flow by fluid resuscitation may prevent systemic hyperlactatemia and therefore mask splanchnic ischemia. ⋯ We conclude that the hepatic lactate uptake increases in response to hepatic lactate influx. Systemic hyperlactatemia and increased hepatic venous lactate concentrations are late consequences of mesenteric hypoperfusion if hypovolemia is prevented. The net exchange of lactate across the splanchnic region does not reflect hepato-portal lactate kinetics in this animal model of intestinal hypoperfusion.
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This study was undertaken to examine the role of lactate on cardiac function and metabolism after severe acute hemorrhagic shock. Anesthetized, nonheparinized rats were bled to a mean arterial pressure of 25-30 mm Hg for 1 h; controls were not bled. Their hearts were removed, and cardiac work and efficiency (work/oxygen consumption) were measured in the isolated working heart mode for 60 min. ⋯ Compared to control hearts, shocked hearts exhibited a 20-30% decrease in PDH activity. Shocked hearts perfused with lactate demonstrated no increase in acetyl CoA content but did have a significant increase in tissue succinyl CoA compared to control hearts perfused with lactate or shocked hearts perfused without lactate. In the heart recovering from severe hemorrhagic shock, lactate improves cardiac efficiency in the presence of free fatty acids, possibly by a anaplerosis of the tricarboxylic acid cycle.
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We have demonstrated previously that dichloroacetate (DCA) treatment in rodents ameliorates, via activation of the pyruvate dehydrogenase complex, the cardiovascular depression observed after hemorrhagic shock. To explore the mechanism of this effect, we administered DCA in a large animal model of hemorrhagic shock. Mongrel hounds were anesthetized with 1.5% isoflurane and were measured for hemodynamics, myocardial contractility, and myocardial substrate utilization. ⋯ However, DCA treatment was associated with a decreased stroke volume index (0.56 +/- 0.06 vs. 0.82 +/- 0.08 mL/kg/beat) and a decreased myocardial efficiency (19 vs. 41 L x mm Hg/mL/100 g tissue). During resuscitation by DCA, myocardial lactate consumption was reduced (21.4 +/- 3.7 vs. 70.7 +/- 16.3 micromole/min/100 g tissue) despite a three-fold increase in myocardial pyruvate dehydrogenase activity, while free fatty acid levels actually began to rise. Although increased lactate oxidation should be beneficial during resuscitation, we propose that DCA treatment led to a deprivation of myocardial lactate supply, which reduced net myocardial lactate oxidation, thus compromising myocardial function during resuscitation from hemorrhagic shock.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Prospectively validated prediction of organ failure and hypotension in patients with septic shock: the Systemic Mediator Associated Response Test (SMART).
Conventional outcomes research provides only percentage risk categories that are not applicable to individual patients, and it predicts only mortality, utilization of resources and/or broad groupings of multiple organ system dysfunction. The purpose of the present study was to determine whether or not the Systemic Mediator Associated Response Test (SMART) methodology could identify interactions among demographics, physiologic parameters, standard hospital laboratory tests, and circulating cytokine concentrations to predict continuous and dichotomous dependent clinical variables, in advance, in individual patients with septic shock and to integrate these into prospectively validated models. Two hundred forty (240) patients with septic shock who were entered into the placebo arm of a multi-institutional clinical trial were randomly separated into a model building training cohort (n = 154) and a predictive cohort (n = 86), which was used to prospectively validate the prognostic models built upon the training cohort database. ⋯ For hematologic/coagulation models, 37/56 (66%) up to seven days had r > 0.900. Among dichotomous models, ROC AUC > 0.700 was achieved in 30/49 (61%) during the first week. SMART integration of demographics, bedside physiology, hospital laboratory tests, and circulating cytokines predicts organ failure and physiologic function indicators in individual patients with septic shock.
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Apoptosis is a mode of programmed cell death (PCD). Transduction of apoptotic signals results in cellular suicide. Organ specific apoptosis has been proposed as a factor in multiple organ dysfunction syndrome (MODS). ⋯ TNF-alpha and IL-6, although they appear to be mediators of both apoptosis and MODS, had no association with sfas. These results are suggestive of the need for further investigation on the role of apoptotic signaling in the development of MODS. They also suggest a potential prognostic value of sfas for SIRS/MODS clinical outcomes.