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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Hypertonic sodium pyruvate (HSP), as well as ethyl pyruvate solutions, has been proposed as resuscitative fluids in the treatment of hemorrhagic shock (HS) because of their anti-inflammatory and antioxidant properties. The effectiveness of one pyruvate preparation over the other in the treatment of HS has not been evaluated. The authors aimed to compare two pyruvate solutions for resuscitation and their mechanisms of action in rats during HS. ⋯ In comparison with Ringer's ethyl pyruvate, HSP administration after hemorrhage reduced liver injury, which was associated with increased levels of serum and tissue inflammatory cytokines, inflammatory mediators such as NOS and cyclooxygenase 2, lipid peroxidation, and higher hepatocellular adenosine triphosphate. Cellular apoptotic events related to the activation of caspase-3 and poly(ADP-ribose)polymerase cleavage were also decreased by sodium pyruvate. Resuscitation with small-volume HSP offers significant protection against inflammatory and oxidative stress and in preventing liver injury compared with large-volume Ringer's ethyl pyruvate.
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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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Pharmacological protection from myocardial reperfusion injury, despite plenty of approaches, has still not been realized in humans. We studied the putative infarct size (IS)-sparing capacity of poly(ADP-ribose)polymerase inhibitor, INO-1001, and focused on cardiac functional recovery during reperfusion. Male farm-bred Landrace pigs were subjected to 1-h left anterior descending coronary artery occlusion followed by 3 h of reperfusion (control). ⋯ Ischemic preconditioning reduced myocardial damage reflected by a smaller IS and lower plasma markers of myocardial injury. INO-1001 did not reduce IS but significantly improved functional recovery (increased stroke volume, cardiac index, and mixed venous oxygen saturation) during reperfusion compared with vehicle-treated control and ischemic preconditioning. Although we could not confirm the IS-sparing capacities of poly(ADP-ribose)polymerase inhibitor, INO-1001, the drug holds the potential of hemodynamic improvement during reperfusion.