Protective effects of nitric oxide synthase 3 and soluble guanylate cyclase on the outcome of cardiac arrest and cardiopulmonary resuscitation in mice.
Protective effects of nitric oxide synthase 3 and soluble guanylate cyclase on the outcome of cardiac arrest and cardiopulmonary resuscitation in mice.
复制标题
DOI：
10.1097/ccm.0b013e318192face
复制
发表时间：
2009-01
影响因子：
8.8
通讯作者：
Ichinose F
中科院分区：
文献类型：
--
作者：
Nishida T;Yu JD;Minamishima S;Sips PY;Searles RJ;Buys ES;Janssens S;Brouckaert P;Bloch KD;Ichinose F
尽管复苏方法有所进步，院外心脏骤停后的存活率仍然很低，至少部分原因是心脏骤停后循环和神经功能衰竭。为了阐明一氧化氮（NO）在心脏骤停和心肺复苏中的作用，我们研究了NOS3/cGMP信号对心脏骤停和心肺复苏（CPR）后心脏和神经系统预后的影响。雌性野生型小鼠（WT）、NOS3缺失小鼠（NOS3−/−）、心肌细胞特异性NOS3过表达的NOS3−/−小鼠（NOS3−/−CSTg）和可溶性鸟苷酸环化酶α1缺失小鼠（sGCα1−/−）接受钾诱导的心脏骤停（9分钟），随后进行心肺复苏。心肺复苏术后24小时评估心脏和神经功能及生存率。心脏骤停和心肺复苏术明显抑制NOS3−/−和sGCα1−/−的心肌功能，但对WT和NOS3−/−CSTg无明显影响。与WT和NOS3−/−CSTg相比，NOS3−/−和sGCα1−/−组的神经功能评分和24小时存活率较低。NOS3或sgc - α1缺乏的有害影响与心脏和肝脏炎症加剧以及心脏、肝脏和大脑细胞死亡增加有关，而心肌细胞限制NOS3的过表达在很大程度上阻止了这一过程。这些结果表明NOS3/sGC信号对心脏骤停的结果有重要的有益影响。心肌NOS3预防心脏骤停后心肌功能障碍，减轻终末器官损伤，改善神经预后和生存。我们的观察表明，增强心脏NOS3和/或sGC活性可能改善心脏骤停和心肺复苏后的预后。
Despite advances in resuscitation methods, survival after out-of-hospital cardiac arrest remains very low, at least in part due to post cardiac arrest circulatory and neurological failure. To elucidate the role of nitric oxide (NO) in the recovery from cardiac arrest and CPR, we studied the impact of NOS3/cGMP signaling on cardiac and neurological outcomes after cardiac arrest and cardiopulmonary resuscitation (CPR). Prospective, randomized, controlled study Animal research laboratory Mice Female wild-type mice (WT), NOS3-deficient mice (NOS3−/−), NOS3−/− mice with cardiomyocyte-specific overexpression of NOS3 (NOS3−/−CSTg), and mice deficient for soluble guanylate cyclase α1 (sGCα1−/−) were subjected to potassium-induced cardiac arrest (9 min) followed by CPR. Cardiac and neurological function and survival were assessed up to 24h post-CPR. Cardiac arrest and CPR markedly depressed myocardial function in NOS3−/− and sGCα1−/− but not in WT and NOS3−/−CSTg. Neurological function score as well as 24h survival rate was lower in NOS3−/− and sGCα1−/− compared to WT and NOS3−/−CSTg. Detrimental effects of deficiency of NOS3 or sGCα1 were associated with enhanced inflammation of heart and liver and increased cell death in heart, liver, and brain that were largely prevented by cardiomyocyte-restricted NOS3 overexpression. These results demonstrate an important salutary impact of NOS3/sGC signaling on the outcome of cardiac arrest. Myocardial NOS3 prevented post-cardiac arrest myocardial dysfunction, attenuated end-organ damage, and improved neurological outcome and survival. Our observations suggest that enhancement of cardiac NOS3 and/or sGC activity may improve outcome after cardiac arrest and CPR.