Inhaled nitric oxide improves outcomes after successful cardiopulmonary resuscitation in mice.
Inhaled nitric oxide improves outcomes after successful cardiopulmonary resuscitation in mice.
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DOI：
10.1161/circulationaha.111.025395
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发表时间：
2011-10-11
期刊：
影响因子：
37.8
通讯作者：
Ichinose F
中科院分区：
文献类型：
--
作者：
Minamishima S;Kida K;Tokuda K;Wang H;Sips PY;Kosugi S;Mandeville JB;Buys ES;Brouckaert P;Liu PK;Liu CH;Bloch KD;Ichinose F
Sudden cardiac arrest (CA) is a leading cause of death worldwide. Breathing nitric oxide (NO) reduces ischemia-reperfusion (IR) 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 min 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 parts per million (ppm) NO for 23h. Mice that were subjected to CA/CPR and breathed air exhibited a poor 10-day survival rate (4/13), depressed neurological and left ventricular (LV) function, and increased caspase-3 activation and inflammatory cytokine induction in the brain. Magnetic resonance imaging revealed brain regions with marked water diffusion abnormality 24h after CA/CPR in mice that breathed air. Breathing air supplemented with NO for 23h starting 1h after CPR attenuated neurological and LV dysfunction 4 days after CA/CPR and markedly improved 10-day survival rate (11/13, P=0.003 vs 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 NOx levels. Deficiency of the α1 subunit of soluble guanylate cyclase (sGC), 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 sGC-dependent mechanisms.
