CARDIOVASCULAR EFFECTS OF NA+/H+ EXCHANGER INHIBITION WITH BIIB513 FOLLOWING HYPOVOLEMIC CIRCULATORY SHOCK
CARDIOVASCULAR EFFECTS OF NA+/H+ EXCHANGER INHIBITION WITH BIIB513 FOLLOWING HYPOVOLEMIC CIRCULATORY SHOCK
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DOI：
10.1097/01.shk.0000150774.93741.26
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发表时间：
2005-03
期刊：
影响因子：
3.1
通讯作者：
Dongmei Wu;Jorge A. Bassuk;J. Arias;H. Doods;J. Adams
中科院分区：
文献类型：
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作者：
Dongmei Wu;Jorge A. Bassuk;J. Arias;H. Doods;J. Adams
Na+/H+交换（NHE）参与心肌缺血再灌注损伤。本研究的目的是通过使用有效的NHE-1选择性抑制剂BIIB 513来研究NHE在低血容量循环休克中的作用。14只猪通过放血（30 mL/kg，30 min）诱导急性快速出血。7头猪用作盐水对照。其他7只猪在出血后30分钟接受3 mg/kg BIIB 513。每个实验包括2小时的低血容量，随后2小时的液体复苏。一只对照动物在实验完成前死亡。另外六只对照动物在整个实验中存活。相比之下，所有BIIB 513给药动物均在整个方案中存活。急性快速失血导致心肌功能受损以及严重的血流动力学和代谢改变。阻断NHE可减轻低血容量性低血压，改善心肌功能。NHE阻断还减轻了代谢性酸中毒，改善了组织氧输送，并改善了复苏后的心脏功能。BIIB 513治疗组中肌酸磷酸激酶（CPK）和心肌肌钙蛋白-I的循环水平显著较低。这些结果表明，NHE激活在低血容量循环休克中起着重要的病理生理作用，NHE-1阻断是改善长期低血容量循环休克复苏的心血管结局的有力干预措施。
Na+/H+ exchange (NHE) is involved in the myocardial injury that occurs during ischemia and reperfusion. The goal of the present study was to investigate the role of NHE in hypovolemic circulatory shock by using a potent NHE-1 selective inhibitor BIIB513. Acute rapid hemorrhage was induced in 14 pigs by bleeding (30 mL/kg over 30 min). Seven pigs were used as saline control. Seven other pigs received 3 mg/kg BIIB513 at 30 min after hemorrhage. Each experiment consisted of 2 h of hypovolemia followed by 2 h of fluid resuscitation. One control animal died before the experiment was completed. Six other control animals survived the entire experiment. In contrast, all the BIIB513 treated animals survived the entire protocol. Acute rapid blood loss resulted in impaired myocardial performance as well as severe hemodynamic and metabolic alterations. NHE blockade attenuated the hypovolemic hypotension and improved myocardial performance. NHE blockade also attenuated the metabolic acidosis, improved tissue oxygen delivery, and improved cardiac function from resuscitation. The circulating levels of creatine phosphokinase (CPK) and cardiac troponin-I were significantly lower in the BIIB513 treatment group. These results suggest that NHE activation plays an important pathophysiological role in hypovolemic circulatory shock, and NHE-1 blockade is a powerful intervention to improve cardiovascular outcomes of resuscitation from prolonged hypovolemic circulatory shock.