Cardioprotective effects of hydrogen sulfide.
Cardioprotective effects of hydrogen sulfide.
复制标题
硫化氢的心脏保护作用。
DOI：
10.1016/j.niox.2010.11.001
复制
发表时间：
2011-08-01
期刊：
影响因子：
--
通讯作者：
Szabó C
中科院分区：
文献类型：
--
作者：
Szabó G;Veres G;Radovits T;Gero D;Módis K;Miesel-Gröschel C;Horkay F;Karck M;Szabó C
气态介质硫化氢（H2S）主要由心脏中的胱硫醚γ-裂解酶合成，并在心血管稳态调节中起作用。在这里，我们首先概述了文献中关于H2S在各种心脏损伤模型中的心脏保护作用的最新技术水平。随后，我们提出了原始数据显示的有益影响，肠外给药的供体H2S的心肌和内皮功能在犬实验模型的心肺转流再灌注。文献综述表明，H2S的各种制剂在培养的细胞、离体心脏以及各种啮齿动物和大型动物局部或整体心肌缺血和心力衰竭模型中发挥心脏保护作用。此外，H2S的产生在心肌预处理和后处理反应中起作用。H2S的心脏保护作用涉及多种途径，包括KATP通道、线粒体呼吸调节和细胞保护基因（如Nrf-2）调节。在本文的实验部分，我们证明了H2S在犬心肺转流手术模型中的心脏保护作用。麻醉犬接受低温心肺转流，在盐水（对照，n=8）或H2S输注（1 mg/kg/h，持续2 h）存在下低温心脏停搏60分钟。在基线和再灌注60分钟后测量左心室血流动力学变量（通过联合压力-容积-电导导管）以及冠状动脉血流量、乙酰胆碱内皮依赖性血管舒张和硝普钠内皮非依赖性血管舒张。离体血管功能和高能磷酸盐含量也进行了测量。再灌注60分钟后，H2S导致前负荷可恢复的每搏功恢复显著更好（p<0.05）。H2S组的冠状动脉血流量也显著较高（p<0.05）。虽然两组对硝普钠的血管舒张反应相似，但乙酰胆碱导致H2S治疗组体内和离体冠状动脉血流量显著增加（p<0.05）。此外，高能磷酸盐含量更好地保存在H2S组。此外，H2S的细胞保护作用也证实了在体外细胞培养实验中H9 c2心肌细胞暴露于缺氧和复氧或细胞毒性氧化剂过氧化氢。因此，H2S的治疗性给药在多种实验模型中发挥心脏保护作用，包括在低温心脏骤停的心肺转流犬模型中显著改善心肌和内皮功能的恢复。
The gaseous mediator hydrogen sulfide (H2S) is synthesized mainly by cystathionine gamma-lyase in the heart and plays a role in the regulation of cardiovascular homeostasis. Here we first overview the state of the art in the literature on the cardioprotective effects of H2S in various models of cardiac injury. Subsequently, we present original data showing the beneficial effects of parenteral administration of a donor of H2S on myocardial and endothelial function during reperfusion in a canine experimental model of cardiopulmonary bypass. Overview of the literature demonstrates that various formulations of H2S exert cardioprotective effects in cultured cells, isolated hearts and various rodent and large animal models of regional or global myocardial ischemia and heart failure. In addition, the production of H2S plays a role in myocardial pre- and post-conditioning responses. The pathways implicated in the cardioprotective action of H2S are multiple and involve KATP channels, regulation of mitochondrial respiration, and regulation of cytoprotective genes such as Nrf-2. In the experimental part of the current article, we demonstrate the cardioprotective effects of H2S in a canine model of cardiopulmonary bypass surgery. Anesthetized dogs were subjected hypothermic cardiopulmonary bypass with 60 minutes of hypothermic cardiac arrest in the presence of either saline (control, n=8), or H2S infusion (1 mg/kg/h for 2 h). Left ventricular hemodynamic variables (via combined pressure-volume-conductance catheter) as well as coronary blood flow, endothelium-dependent vasodilatation to acetylcholine and endothelium-independent vasodilatation to sodium nitroprusside were measured at baseline and after 60 minutes of reperfusion. Ex vivo vascular function and high-energy phosphate contents were also measured. H2S led to a significantly better recovery of preload recruitable stroke work (p<0.05) after 60 minutes of reperfusion. Coronary blood flow was also significantly higher in the H2S group (p<0.05). While the vasodilatory response to sodium nitroprusside was similar in both groups, acetylcholine resulted in a significantly higher increase in coronary blood flow in the H2S-treated group (p<0.05) both in vivo and ex vivo. Furthermore, high-energy phosphate contents were better preserved in the H2S group. Additionally, the cytoprotective effects of H2S were confirmed also using in vitro cell culture experiments in H9c2 cardiac myocytes exposed to hypoxia and reoxygenation or to the cytotoxic oxidant hydrogen peroxide. Thus, therapeutic administration of H2S exerts cardioprotective effects in a variety of experimental models, including a significant improvement of the recovery of myocardial and endothelial function in a canine model of cardiopulmonary bypass with hypothermic cardiac arrest.
登录
查看更多内容
影响因子：
20.1
作者：
Calvert JW;Jha S;Gundewar S;Elrod JW;Ramachandran A;Pattillo CB;Kevil CG;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
37.8
作者：
Calvert JW;Elston M;Nicholson CK;Gundewar S;Jha S;Elrod JW;Ramachandran A;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
5
作者：
Pan, TT;Feng, ZN;Bian, JS
通讯作者：
Bian, JS
DOI：
10.1124/jpet.105.092023
发表时间：
2006-02-01
影响因子：
3.5
作者：
Bian, JS;Yong, QC;Moore, PK
通讯作者：
Moore, PK
影响因子：
4.7
作者：
Hu, Li-Fang;Wong, Peter T. -H.;Bian, Jin-Song
通讯作者：
Bian, Jin-Song