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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Transcutaneous pressure of oxygen: a noninvasive and early detector of peripheral shock and outcome.
A noninvasive tool to recognize early shock would improve outcome by providing prompt recognition of tissue ischemia and precise resuscitation endpoint. The skin is the first tissue bed to vasoconstrict in shock states. Studies have demonstrated that transcutaneous partial pressure of oxygen (PtCO2) increases with higher FiO2 in nonshock states as arterial pressure of oxygen (PaO2) increases, but in shock situations, PtCO2 mirrors changes in cardiac output and oxygen delivery with minimum response to increasing FiO2 and PaO2. ⋯ Measurements included hemodynamic variables, PtCO2, and outcome (mortality and organ failure). In this study, the ability of PtCO2 value to increase by 21 mmHg on a FiO2 of 1.0, at 24 h of resuscitation, divided survivors from nonsurvivors, P <.001. The PtCO2 response to FiO2 may provide an additional noninvasive method of detecting early shock as well as a specific endpoint of resuscitation.
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Awake hamsters equipped with the dorsal window chamber preparation were subjected to hemorrhage of 50% of the estimated blood volume. Initial resuscitation (25% of estimated blood volume) with polymerized bovine hemoglobin (PBH) or 10% hydroxyethyl starch (HES) occurred in concert with an equivolumetric bleeding to simulate the early, prehospital setting (exchange transfusion). Resuscitation (25% of estimated blood volume) without bleeding was performed with PBH, HES, or autologous red blood cells (HES-RBCs). ⋯ In conclusion, the PBH led to a correction of base deficit comparable to blood transfusion. However, oxygenation of the peripheral tissue was inferior with PBH. This was attributed to its negative impact on the peripheral microcirculation caused by arteriolar vasoconstriction.
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In severe sepsis and septic shock, hemodynamic support is often complicated by a tachyphylaxis against exogenous catecholamines. Because activation of adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels plays a pivotal role in the pathogenesis of hyperdynamic vasodilatory shock, we hypothesized that it may be beneficial to administer a specific K(ATP) channel inhibitor to prevent, or at least attenuate, hemodynamic dysfunction in sepsis. The present study was designed as a prospective and controlled laboratory experiment to elucidate the short-term effects of glipizide, a specific K(ATP) channel inhibitor, on cardiopulmonary hemodynamics and global oxygen transport in healthy sheep and sheep with endotoxemia. ⋯ Cardiac index, oxygen delivery index, arterial lactate concentrations, and arterial pH were not significantly affected by glipizide. Therefore, administration of glipizide may represent a beneficial therapeutic option to treat arterial hypotension resulting from sepsis and systemic inflammatory response syndrome. Additional studies are required to determine the effects of continuous infusion of glipizide in the presence of systemic inflammation.
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Insulin resistance after burn is associated with alterations in postreceptor insulin signaling and abnormal glucose homeostasis. The renin-angiotensin system (RAS) exerts a largely inhibitory role on insulin action and is activated after burn injury. We hypothesized that upregulation of RAS is involved in the development of insulin resistance in burned rats. ⋯ There was an increase in the area under the curve for insulin and the glucose insulin index in burn placebo group as compared with sham-burned group, indicating insulin resistance. Losartan treatment abolished the insulin resistance in burn as evidenced by an area under the curve for insulin and glucose insulin index lower than that in the burn placebo group and similar to that in the sham-burned group. This suggests that insulin resistance and glucose intolerance associated with burn injury is, in part, caused by RAS.
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The peroxisome proliferator-activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid, and thyroid hormone receptors. The aim of the present study is to evaluate the role of PPAR-alpha receptor on the development of multiple-organ dysfunction syndrome (MODS) induced by zymosan. MODS was induced by peritoneal injection of zymosan (dose, 500 mg/kg i.p. as a suspension in saline) in PPAR-alpha wild-type (PPAR-alphaWT) and PPAR-alpha knockout (PPAR-alphaKO) mice, was assessed 18 h after the administration of zymosan, and was monitored for 12 days (for loss of body weight and mortality). ⋯ In contrast, the degree of (1) peritoneal inflammation and tissue injury, (2) nitrotyrosine formation and Fas ligand expression, and (3) neutrophil infiltration were markedly enhanced in intestinal tissue obtained from zymosan-treated PPAR-alphaKO mice. Zymosan-treated PPAR-alphaKO mice also showed a significantly increased mortality. Taken together, the present study clearly demonstrates that PPAR-alpha pathway modulates the degree of MODS associated with zymosan-induced nonseptic shock.