Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3-dependent mechanism in mice.
Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3-dependent mechanism in mice.
复制标题
硫化氢通过一氧化氮合酶 3 依赖性机制提高小鼠心脏骤停和心肺复苏后的存活率。
DOI：
10.1161/circulationaha.108.833491
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发表时间：
2009-09-08
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;Bougaki M;Sips PY;Yu JD;Minamishima YA;Elrod JW;Lefer DJ;Bloch KD;Ichinose F
心脏骤停（CA）是全球主要的死亡原因之一。我们试图评估硫化氢（H2S）对小鼠CA和心肺复苏（CPR）后结局的影响。使小鼠经受8分钟的常温CA，并通过胸部按压和机械通气复苏。CA发作后7分钟，小鼠接受硫化钠（Na 2S，0.55mg/kg i. v.）CPR前1分钟或溶剂。两组的自主循环恢复率（ROSC）、CPR至ROSC的时间和ROSC时的左心室（LV）功能无差异。CPR前1 min给予Na 2S显著改善了CPR后24 h的存活率（15/15），与溶媒组相比（10/26，P=0.0001 vs Na 2S）。给予Na 2S可预防CA/CPR诱导的氧化应激，并改善CPR后24 h的LV和神经功能障碍。CPR后10分钟延迟给予Na 2S并不能改善CA/CPR后的结局。在离体灌流的小鼠全脑缺血和再灌注心脏中证实了Na 2S的心脏保护作用。心肌细胞特异性过表达胱硫醚γ-裂解酶（CGL，一种产生H2S的酶）可显著改善CA/CPR的结局。Na 2S增加了LV和脑皮质中NOS 3的磷酸化，增加了血清亚硝酸盐/硝酸盐水平，并减弱了CA诱导的线粒体损伤和细胞死亡。NOS 3缺乏可使Na 2S对CA/CPR预后的保护作用消失。这些结果表明，在CPR时给予Na 2S可能通过NOS 3依赖性信号通路改善心脏骤停后的结果。
Sudden cardiac arrest (CA) is one of the leading causes of death worldwide. We sought to evaluate the impact of hydrogen sulfide (H2S) on the outcome after CA and cardiopulmonary resuscitation (CPR) in mouse. Mice were subjected to 8 min of normothermic CA and resuscitated with chest compression and mechanical ventilation. Seven minutes after the onset of CA, mice received sodium sulfide (Na2S, 0.55 mg/kg i.v.) or vehicle 1 min before CPR. There was no difference in the rate of return of spontaneous circulation (ROSC), CPR time to ROSC, and left ventricular (LV) function at ROSC between groups. Administration of Na2S 1 min before CPR markedly improved survival rate at 24h after CPR (15/15) compared to vehicle (10/26, P=0.0001 vs Na2S). Administration of Na2S prevented CA/CPR-induced oxidative stress and ameliorated LV and neurological dysfunction 24h after CPR. Delayed administration of Na2S at 10 min after CPR did not improve outcomes after CA/CPR. Cardioprotective effects of Na2S were confirmed in isolated-perfused mouse hearts subjected to global ischemia and reperfusion. Cardiomyocyte-specific overexpression of cystathionine γ-lyase (CGL, an enzyme that produces H2S) markedly improved outcomes of CA/CPR. Na2S increased phosphorylation of NOS3 in LV and brain cortex, increased serum nitrite/nitrate levels, and attenuated CA-induced mitochondrial injury and cell death. NOS3 deficiency abrogated the protective effects of Na2S on the outcome of CA/CPR. These results suggest that administration of Na2S at the time of CPR improves outcome after cardiac arrest possibly via an NOS3-dependent signaling pathway.