Mechanisms of the beneficial effect of NHE1 inhibitor in traumatic hemorrhage: Inhibition of inflammatory pathways

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• 作者：Dongmei Wu^a ; ^b ; ^{dongmeiwu@bellsouth.net} ; ^{dongmei@jbnu.ac.kr} ; Jiansong Qi^a
• 关键词：Myocardial dysfunction ; Traumatic hemorrhagic shock ; Organ injury ; Inflammatory response
• 刊名：Resuscitation
• 出版年：2012
• 期刊代码：236_03009572
• 类别：med
• 出版时间：June, 2012
• 卷：83
• 期：6
• 页码：774-781
• 文件大小：808 K

摘要

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 4 mm hepatic arterial tear with surgical repair after 20 min. Animals then underwent low volume fluid resuscitation with either hextend (n = 6) or 3 mg/kg BIIB513 (NHE1 inhibitor) + hextend (n = 6). The experiment was terminated 6 h 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-魏B 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-魏B activation and neutrophil infiltration, reducing iNOS expression and ERK1/2 phosphorylation, thereby, reducing systemic inflammation and thus multi-organ injury.