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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We investigated the acute microcirculatory effects, including mesenteric lymphatic pumping, of volume replacement with different iso- or hypertonic/oncotic solutions after severe hemorrhage (mean arterial pressure [MAP] approximately 35 mmHg during 30 min) in halothane-anesthetized Wistar rats. Resuscitation was achieved 30 min after induction of shock with one of the following solutions: autologous blood (BL); 0.9% NaCl (IS), 7.5% NaCl (HS); 5% bovine serum albumin (BSA); 0.9% NaCl-6% hydroxyethyl starch (HES), or 7.5% NaCl-HES (HES 7.5). MAP was partially and transiently restored by infusion of IS or HS, whereas in the groups treated with BL, HES, HES 7.5, or BSA, there was a complete restoration of blood pressure in the 30-min period after infusion. ⋯ On the other hand, resuscitation with all other solutions, except BSA, did not restore lymphatic activity to preshock levels. We also observed a significant reduction of the diameter of mesenteric terminal arterioles (15-30 microm) after bleeding, which was reversed temporarily in IS, BL, and HES groups, whereas resuscitation with HES 7.5 solution was able to maintain arterioles dilated until the end of the experimental period. Therefore, it is concluded that the association of hyperoncotic and hyperosmotic solutions, represented here by HES 7.5, induces positive effects with respect to the macro- and microhemodynamics accompanied by restoration and maintenance of the interstitial drainage system, being indicated for maintenance of postresuscitation cardiovascular and microvascular function.
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Neutrophil migration to an infectious focus is essential for control and resolution of infection. Early studies demonstrated that the failure of such migration is observed in lethal sepsis induced by cecal ligation and puncture (L-CLP), whereas intense neutrophil migration is seen in sublethal CLP (SL-CLP). In this study, we found that inhibition of synthesis of prostaglandins or leukotriene B4 (LTB4) did not modify the failure of neutrophil migration or the survival rate of L-CLP mice. ⋯ Both SL-CLP and L-CLP animals presented significant levels of LTB4 in the peritoneal exudate (3- and 8-fold higher than sham group, respectively) and these were reduced by the pretreatment of mice with LTB4 inhibitors. In conclusion, our results suggest that LTB4, but not prostaglandins or PAF, is an important chemoattractant involved in neutrophil recruitment to infection sites in SL-CLP, a crucial event in confining the invading pathogens to a restricted area. However, in circumstances in which the infection turns to a lethal sepsis, LTB4 is not involved in the observed failure of neutrophil migration to the infectious focus.
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This study was aimed to determine whether administration of an inhibitor of caspase-3 protects hepatocellular function in rats with hemorrhagic shock and whether caspases are important pharmacological targets in attenuating liver injury induced by hemorrhagic shock and resuscitation. Male adult rats were subjected to hemorrhagic shock by bleeding to a mean arterial blood pressure of 35-40 mmHg for 1 h and were then resuscitation with 60% shed blood and lactated Ringers solution. A subgroup of animals was injected i.v. with 2 mg/kg caspase inhibitor, Z-DEVD-FMK, prior to blood withdrawal. ⋯ The cytosolic concentration of thiobarbituric acid-reactive substances (TBARS) and the oxidized:reduced glutathione ratio increased in the animals with hemorrhagic shock (+94% and +170%, respectively). These parameters were not significantly modified by pretreatment with Z-DEVD-FMK. It appears that caspase inhibition does not attenuate hepatocellular depression and liver injury induced by hemorrhagic shock and resuscitation.