Department of Research, Mount Sinai Medical Center, Miami Beach, FL, USA.
Resuscitation. 2013 Apr;84(4):520-5. doi: 10.1016/j.resuscitation.2012.08.334. Epub 2012 Sep 16.
The present study investigated the protective effects of a novel NHE1 selective inhibitor, sabiporide, in a porcine model of asphyxia-induced cardiac arrest. Asphyxial cardiac arrest was induced by endotracheal tube clamping (ETC). The animals remained untreated for 3 min after loss of aortic pulsations (LOAP), and followed by chest compression and defibrillation. Sixteen of eighteen pigs had return of spontaneous circulation (ROSC), and were randomly assigned to two study groups. Group 1: vehicle control. Group 2: 3mg/kg sabiporide was given at 15 min after ROSC. Post-arrest myocardial dysfunction was present in both groups, and progressed over hours. Animals treated with sabiporide had less wall motion abnormality and higher left ventricular ejection fraction than control animals (33% in control group vs. 47% in sabiporide group). Sabopiride treatment also significantly improved post-arrest arterial blood pressure by 25% and cardiac stroke volume by 44%, and improved mixed-venous blood oxygen saturation by 38% and oxygen delivery by 118%. Furthermore, compared to the control group, the sabiporide group also had higher blood flows in the brain, heart, kidney, liver and spleen at 30 min after ROSC. There was no significant blood flow difference in distal ileum mucosa between control and sabiporide groups. In addition, sabiporide treatment significantly reduced cardiac myeloperoxidase (MPO) activity by 53% and cardiac troponin I by 51%, and reduced the plasma level of TNF-α by 52% and IL-6 by 41%. This study shows that post-arrest pharmacological conditioning with sabiporide affords protection from whole body ischemia-reperfusion injury in this model of asphyxia-induced cardiac arrest and resuscitation.
本研究探讨了新型 NHE1 选择性抑制剂沙比波里德（sabiporide）在猪窒息性心跳骤停模型中的保护作用。窒息性心跳骤停通过气管内插管夹闭（ETC）诱导。动物在主动脉搏动消失（LOAP）后 3 分钟内未进行治疗，随后进行胸部按压和除颤。18 只猪中有 16 只恢复了自主循环（ROSC），并随机分为两组。第 1 组：载体对照。第 2 组：ROSC 后 15 分钟给予 3mg/kg 沙比波里德。两组均存在心跳骤停后心肌功能障碍，并在数小时内进展。用沙比波里德治疗的动物比对照组的室壁运动异常更少，左心室射血分数更高（对照组为 33%，沙比波里德组为 47%）。沙比波里德治疗还显著提高了 25%的心跳骤停后动脉血压和 44%的心脏每搏量，并将混合静脉血氧饱和度提高了 38%，氧输送提高了 118%。此外，与对照组相比，沙比波里德组在 ROSC 后 30 分钟时大脑、心脏、肾脏、肝脏和脾脏的血流量也更高。对照组和沙比波里德组的回肠远端黏膜血流量无显著差异。此外，沙比波里德治疗还显著降低了心脏髓过氧化物酶（MPO）活性 53%和心肌肌钙蛋白 I 51%，降低了 TNF-α 血浆水平 52%和 IL-6 41%。这项研究表明，心跳骤停后用沙比波里德进行药物预处理可在这种窒息性心跳骤停和复苏模型中提供对全身缺血再灌注损伤的保护。
