Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Ghent University, Ghent, Belgium.
Circulation. 2011 Oct 11;124(15):1645-53. doi: 10.1161/CIRCULATIONAHA.111.025395. Epub 2011 Sep 19.
Sudden cardiac arrest (CA) is a leading cause of death worldwide. Breathing nitric oxide (NO) reduces ischemia/reperfusion injury in animal models and in patients. The objective of this study was to learn whether inhaled NO improves outcomes after CA and cardiopulmonary resuscitation (CPR).
Adult male mice were subjected to potassium-induced CA for 7.5 minutes whereupon CPR was performed with chest compression and mechanical ventilation. One hour after CPR, mice were extubated and breathed air alone or air supplemented with 40 ppm NO for 23 hours. Mice that were subjected to CA/CPR and breathed air exhibited a poor 10-day survival rate (4 of 13), depressed neurological and left ventricular function, and increased caspase-3 activation and inflammatory cytokine induction in the brain. Magnetic resonance imaging revealed brain regions with marked water diffusion abnormality 24 hours after CA/CPR in mice that breathed air. Breathing air supplemented with NO for 23 hours starting 1 hour after CPR attenuated neurological and left ventricular dysfunction 4 days after CA/CPR and markedly improved 10-day survival rate (11 of 13; P=0.003 versus mice breathing air). The protective effects of inhaled NO on the outcome after CA/CPR were associated with reduced water diffusion abnormality, caspase-3 activation, and cytokine induction in the brain and increased serum nitrate/nitrite levels. Deficiency of the α1 subunit of soluble guanylate cyclase, a primary target of NO, abrogated the ability of inhaled NO to improve outcomes after CA/CPR.
These results suggest that NO inhalation after CA and successful CPR improves outcome via soluble guanylate cyclase-dependent mechanisms.
心脏骤停（CA）是全球范围内主要的死亡原因。呼吸一氧化氮（NO）可减少动物模型和患者中的缺血/再灌注损伤。本研究的目的是了解吸入 NO 是否能改善 CA 和心肺复苏（CPR）后的结果。
成年雄性小鼠接受钾诱导的 CA 7.5 分钟，随后进行胸外按压和机械通气的 CPR。CPR 后 1 小时，将小鼠拔出气管插管，单独呼吸空气或空气补充 40ppmNO 23 小时。接受 CA/CPR 并呼吸空气的小鼠 10 天存活率差（13 只中有 4 只），神经和左心室功能下降，大脑中 caspase-3 激活和炎性细胞因子诱导增加。磁共振成像显示，在接受 CA/CPR 并呼吸空气的小鼠中，CA/CPR 后 24 小时大脑出现明显的水扩散异常区域。CPR 后 1 小时开始吸入 23 小时补充 40ppmNO 可减轻 CA/CPR 后 4 天的神经和左心室功能障碍，并显著提高 10 天存活率（13 只中有 11 只；P=0.003，与呼吸空气的小鼠相比）。吸入 NO 对 CA/CPR 后结果的保护作用与大脑中水扩散异常、caspase-3 激活和细胞因子诱导减少以及血清硝酸盐/亚硝酸盐水平升高有关。一氧化氮的主要靶标可溶性鸟苷酸环化酶的α1 亚基缺失，削弱了吸入 NO 改善 CA/CPR 后结果的能力。
这些结果表明，CA 后成功 CPR 并吸入 NO 通过可溶性鸟苷酸环化酶依赖性机制改善结果。
