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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The Wnt/β-catenin signaling pathway is well characterized in stem cell biology and plays a critical role in liver development, regeneration, and homeostasis. We hypothesized that pharmacologic activation of Wnt signaling protects against hepatic ischemia/reperfusion (I/R) injury through its known proliferative and antiapoptotic properties. Sprague-Dawley rats underwent 70% hepatic ischemia by microvascular clamping of the hilum of the left and median lobes of the liver for 90 min, followed by reperfusion. ⋯ Wnt agonist also significantly decreased the amount of apoptosis, as evidenced by decreases in both TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining as well as caspase 3 activity levels. Finally, the 10-day survival rate was increased from 27% in the vehicle group to 73% in the pretreated Wnt agonist group and 55% in the Wnt agonist postischemia treatment group. Thus, we propose that direct Wnt/β-catenin stimulation may represent a novel therapeutic approach in the treatment of hepatic I/R.
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Severe crush injury is associated with high mortality because of resulting hyperkalemia in early phase and multiorgan dysfunction in later phase. In this study, we investigated the effects of sivelestat administration 1 h before reperfusion on the outcome of crush injury. Crush injury was induced by 6 h of direct compression to both hindlimbs of anesthetized rats with blocks weighing 3.5 kg each side, followed by 3 h of reperfusion. ⋯ Treatment with sivelestat significantly improved survival rate with P = 0.032. This was accompanied by lower serum high-mobility group box 1 (HMGB1) levels after 3-h reperfusion, attenuated lung injury (assessed using hematoxylin-eosin stain), and suppression of HMGB1 expression in the lung and the liver. These results suggest that treatment with sivelestat improves the outcome of crush injury, likely by inhibiting HMGB1 in rats.
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Multicenter Study Comparative Study Clinical Trial
Central venous oxygen saturation under non-protocolized resuscitation is not related to survival in severe sepsis or septic shock.
Protocolized hemodynamic resuscitation in severe sepsis or septic shock is not universally applied in all emergency departments and general hospital wards around the world. It is unknown whether ScvO2 levels are associated with the clinical outcome of severe sepsis or septic shock under nonprotocolized resuscitation. In this prospective study, we enrolled 124 noncirrhotic patients who were admitted to intensive care units for severe sepsis or septic shock. ⋯ In conclusion, our results showed that mean arterial pressure and central venous pressure were still the most important hemodynamic variables in initial hemodynamic resuscitation. Low postresuscitation ScvO2 was not associated with a worse outcome. It is possible that ScvO2 less than 70% might not necessarily be associated with tissue hypoxia, and critical ScvO2 levels require to be determined by further studies.