Low-volume resuscitation from traumatic hemorrhagic shock with Na+/H+ exchanger inhibitor*
Low-volume resuscitation from traumatic hemorrhagic shock with Na+/H+ exchanger inhibitor*
复制标题
DOI：
10.1097/ccm.0b013e3181a0052e
复制
发表时间：
2009-06
影响因子：
8.8
通讯作者：
Dongmei Wu;Hui Dai;J. Arias;L. Latta;W. Abraham
中科院分区：
文献类型：
--
作者：
Dongmei Wu;Hui Dai;J. Arias;L. Latta;W. Abraham
目的：在两种不同的创伤失血性休克大鼠模型中评价钠离子/氢离子交换剂（NHE-1）抑制剂作为低容量复苏心脏保护辅助治疗的应用。设计：实验性、前瞻性研究。单位：医学中心研究实验室。受试者：Sprague道利雄性大鼠。干预措施：系列1：在麻醉的大鼠中诱导股骨骨折，随后进行压力控制出血（40 mm Hg，20分钟）和复苏。群组：1）无治疗; 3）3 mg/kg苯甲酰胺，N-（氨基亚氨基甲基）-4-[4-（2-呋喃基羰基）-1-哌嗪基]-3-（甲磺酰基），甲磺酸盐（BIIB 513）（NHE-1抑制剂）+15mL/kg羟乙基淀粉，输注40分钟。复苏后6小时终止实验。系列2：大鼠在麻醉下接受剖腹术和闭合术，随后在研究的其余时间保持清醒。如系列1所述，对大鼠进行容量控制出血（2.5 mL/100 g），然后进行复苏。复苏后24小时终止实验。测量和主要结果：系列1：无治疗组的所有动物均在2小时内死亡。与羟乙基淀粉单独输注相比，添加NHE-1抑制剂改善了对液体复苏的血流动力学反应，增加了血氧含量，预防了代谢性酸中毒，并改善了6小时生存率（羟乙基淀粉组为42%，BIIB 513+羟乙基淀粉组为80%）。NHE-1抑制还导致肿瘤坏死因子、细胞间粘附分子-1和C反应蛋白的血浆水平降低，并减弱肝脏中的中性粒细胞浸润。系列2：无治疗组的所有动物均在出血后4小时内死亡。与羟乙基淀粉单独输注相比，添加BIIB 513可改善24小时存活率（羟乙基淀粉组为44%，BIIB 513+羟乙基淀粉组为78%）。NHE-1抑制还降低了复苏后24小时的血浆丙氨酸氨基转移酶水平。结论：NHE-1抑制促进了对液体复苏的血流动力学反应，减轻了组织炎症损伤和器官功能障碍，但最重要的是改善了存活率。
Objective:To evaluate the use of a Na+/H+ exchanger (NHE-1) inhibitor as a cardioprotective adjunct therapy to low-volume resuscitation in two different rat models of traumatic hemorrhagic shock. Design:Experimental, prospective study. Setting:Medical center research laboratory. Subjects:Sprague Dawley male rats. Interventions:Series 1: femur fracture was induced in anesthetized rats, followed by pressure-controlled hemorrhage (40 mm Hg for 20 minutes) and resuscitation. Groups: 1) no therapy; 2) 15 mL/kg hetastarch; and 3) 3 mg/kg benzamide, N-(aminoiminomethyl)-4-[4-(2-furanylcarbonyl)-1-piperazinyl]-3-(methylsulfonyl), methanesulfonate (BIIB513) (NHE-1 inhibitor) + 15 mL/kg hetastarch infusion over 40 minutes. The experiment was terminated at 6 hours after resuscitation. Series 2: the rats received laparotomy and closure under anesthesia and subsequently remained conscious for the rest of the study. The rats were subjected to volume-controlled hemorrhage (2.5 mL/100 g) followed by resuscitation as described in series 1. The experiment was terminated at 24 hours after resuscitation. Measurements and Main Results:Series 1: all animals in the no-therapy group died within 2 hours. Compared with hetastarch infusion alone, the addition of NHE-1 inhibitor improved the hemodynamic response to fluid resuscitation, increased blood oxygen content, prevented metabolic acidosis, and improved 6-hour survival (42% in hetastarch group vs. 80% in BIIB513 + hetastarch group). NHE-1 inhibition also resulted in reduced plasma levels of tumor necrosis factor-, intercellular adhesion molecule-1, and C-reactive protein, and attenuated neutrophil infiltration in the liver. Series 2: all animals in the no-therapy group died within 4 hours after hemorrhage. Compared with hetastarch infusion alone, the addition of BIIB513 improved 24-hour survival (44% in hetastarch group vs. 78% in BIIB513 + hetastarch group). NHE-1 inhibition also reduced plasma levels alanine aminotransferase at 24 hours after resuscitation. Conclusions:NHE-1 inhibition facilitated the hemodynamic response to fluid resuscitation, attenuated tissue inflammatory injury, and organ dysfunction, but most importantly improved survival.