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- W2034369110 abstract "This study evaluated the effects of sodium-hydrogen exchanger (NHE1) inhibition on enhancing fluid resuscitation outcomes in traumatic hemorrhagic shock, and examined the mechanisms related to NHE1 inhibitor-induced protection and recovery from hemorrhagic shock. Traumatic hemorrhage was modeled in anesthetized pigs by producing tibia fractures followed by hemorrhage of 25 ml/kg for 20 min, and then a 4mm hepatic arterial tear with surgical repair after 20 min. Animals then underwent low volume fluid resuscitation with either hextend (n=6) or 3mg/kg BIIB513 (NHE1 inhibitor)+hextend (n=6). The experiment was terminated 6h after the beginning of resuscitation. In association with traumatic hemorrhagic shock, there was a decrease in cardiac index, stimulation of the inflammatory response, myocardial, liver and kidney injury. The administration of the NHE1 inhibitor at the time of resuscitation attenuated shock-resuscitation-induced myocardial hypercontracture and resulted in a significant increase in stroke volume index, compared to vehicle-treated controls. NHE1 inhibition also reduced the inflammatory response, and lessened myocardial, liver and kidney injury. In addition, NHE1 inhibition reduced NF-κB activation and iNOS expression, and attenuated of ERK1/2 phosphorylation. Results from the present study indicate that NHE1 inhibition prevents multiple organ injury by attenuating shock-resuscitation-induced myocardial hypercontracture and by inhibiting NF-κB activation and neutrophil infiltration, reducing iNOS expression and ERK1/2 phosphorylation, thereby, reducing systemic inflammation and thus multi-organ injury." @default.
- W2034369110 created "2016-06-24" @default.
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- W2034369110 date "2012-06-01" @default.
- W2034369110 modified "2023-10-16" @default.
- W2034369110 title "Mechanisms of the beneficial effect of NHE1 inhibitor in traumatic hemorrhage: Inhibition of inflammatory pathways" @default.
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- W2034369110 doi "https://doi.org/10.1016/j.resuscitation.2011.11.025" @default.
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