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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One of the common lethal complications of septic shock, a major cause of morbidity and mortality in patients with severe trauma and so on, is acute lung injury. alpha-Lipoic acid (ALA), with antioxidant properties, is a popular agent. Thus, we investigated the potential protective effects of ALA (200 mg/kg) on sepsis-induced acute lung injury. Rats were exposed to cecal ligation and puncture (CLP) to induce sepsis. ⋯ Sixteen hours after CLP induction, serum samples and lung tissues were obtained for biochemical and histopathological examination. alpha-Lipoic acid decreased the serum levels of inflammatory cytokines such as TNF-alpha and IL-6, which increased after CLP. Increased activity of nuclear factor kappaB in septic lung tissues was decreased by ALA. alpha-Lipoic acid improved the decreased antioxidant activity and alleviated the increased oxidant activity, which occurred after CLP application. We can suggest that ALA showed beneficial effects by decreasing nuclear factor kappaB activation in lung tissues, resulting in decreased serum levels of TNF-alpha and IL-6, and also increasing the antioxidant capacity of the lungs.
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Although patients with obstructive jaundice are susceptible to bacterial infections and cancers, the mechanisms remain to be elucidated. In the present study, liver mononuclear cells (MNCs) of bile duct-ligated (BDL) mice were immunologically assessed. Liver natural killer T cells were greatly decreased within 24 h after BDL. ⋯ IFN-gamma production by liver MNC from normal mice stimulated with LPS in vitro was inhibited by the addition of bile acids, whereas, conversely, the production of IL-12 and IL-18 increased. In conclusion, liver natural killer T cells were diminished in BDL mice, and the function of liver MNC (IFN-gamma production) was also impaired presumably due to increased bile acids. This may partly explain the increased susceptibility of BDL mice to bacterial infections and tumor metastasis.
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Calcium plays an important role in determining vascular smooth muscle tone. Norepinephrine (NE)-induced vascular contraction contains two components: 1) Ca2+ release from the sarcoplasmic reticulum as the fast phase and 2) Ca2+ influx via a voltage-dependent calcium channel as the slow phase. This study used functional isometric tension recording to evaluate mediators contributing to abnormal NE-induced Ca2+ handling and reactivity in isolated thoracic aortas from septic rats. ⋯ Inhibition by 2-aminoethoxy-diphenyl borane, ryanodine, and cyclopiazonic acid of the NE-induced contraction in Ca2+-free solution was greater in the aorta from sepsis rats and inhibitions of cyclopiazonic acid and ryanodine, but not of 2-aminoethoxy-diphenyl borane, were attenuated by NOS inhibitor N[omega]-nitro-l-arginine methyl ester. In addition, the attenuation of NE-induced contraction by nifedipine in the aorta was also greater in the CLP group. Our results suggest that abnormal NE-induced Ca2+ handling associated with vascular hyporeactivity in the CLP-induced sepsis is caused by a major decrease in sarcoplasmic reticulum function and a minor impairment of voltage-dependent Ca2+ channels on membrane to Ca2+ handling, at least, in the aorta, and this could be attributed to an overproduction of NO in sepsis.
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The authors investigated whether the pulse pressure power spectrum (PPPS) could predict the effect of volume expansion (VE) in shock patients under mechanical ventilation without sedation. The PPPS within a frequency band of 0.15 to 0.75 Hz was developed with an animal model using nine domesticated piglets simulating acute hemorrhagic shock and then validated in 17 nonsedated mechanically ventilated shock patients. Hemodynamic parameters were recorded before and after VE. ⋯ The correlations were weaker with PPV120 (r(2)= 0.27 and r(2) = 0.42) and PPV30 (r(2) = 0.27 and r(2)= 0.40). The AROC were 0.78 for SQRT-PPPS (P = 0.047), 0.71 for PPV120 (P = 0.131), and 0.69 for PPV30 (P = 0.185). In mechanically ventilated shock patients, SQRT-PPPS predicts volume responsiveness without the need for sedation to prevent spontaneous breathing movements.
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Sivelestat sodium hydrate is a selective inhibitor of neutrophil elastase, which is effective in acute lung injury associated with systemic inflammatory response syndrome. However, the effectiveness of sivelestat in sepsis has not been fully examined. In the present study, the effect of sivelestat on severe sepsis in a rat cecal ligation and puncture (CLP) model was investigated. ⋯ The lungs from sivelestat-treated rats exhibited less severe pathological changes and decreased the numbers of HMGB1, IL-8, and CD68-positive cells (P < 0.001). Sivelestat significantly improved survival rate of rats with clinically relevant sepsis, possibly by attenuating sepsis-induced systemic inflammatory response and lung injury. This may explain the implicated health benefits of sivelestat in reducing morbidity and mortality from sepsis.