Simon Florian, Giudici Riccardo, Duy Cuong Nguyen, Schelzig Hubert, Oter Sükrü, Gröger Michael, Wachter Ulrich, Vogt Josef, Speit Günter, Szabó Csaba, Radermacher Peter, Calzia Enrico
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Abteilung für Thorax- und Gefäbetachirurgie, Universitätsklinikum, Ulm, Germany.
Shock. 2008 Oct;30(4):359-64. doi: 10.1097/SHK.0b013e3181674185.
In awake spontaneously breathing mice, inhaling gaseous hydrogen sulfide (H2S) produced a "suspended animation-like" metabolic status with hypothermia and reduced O2 demand, thus protecting from lethal hypoxia. Murine models may be questioned, however, because due to their large surface area/mass ratio, rodents can rapidly drop their core temperature. Therefore, we investigated whether intravenous H2S (Na2S, sodium sulfide) would induce a comparable metabolic response in anesthetized and mechanically ventilated pigs. Because H2S was reported to improve heart function after myocardial ischemia, we also investigated whether sulfide would influence the noradrenaline responsiveness during reperfusion after aortic occlusion. After 2 h of i.v. sulfide (0.2 mg.kg followed by 2 mg.kg.per h; n=8) or vehicle (n=8), animals underwent 30 minutes of aortic occlusion with nitroglycerine, esmolol, and adenosine-5'-triphosphate adjusted to maintain MAP at 80% to 120% of baseline. During reperfusion, noradrenaline was titrated to keep MAP greater than or equal to 80% of this level. Sulfide reduced heart rate and cardiac output without affecting stroke volume, markedly decreased the time and dose of noradrenaline required to maintain hemodynamic targets, and caused a drop in core temperature concomitant with lower O2 uptake and CO2 production. Although arterial PCO2 and acid-base status were comparable, arterial PO2 was lower in the sulfide group at the end of the experiment. Sulfide attenuated the reperfusion-related hyperlactatemia, although glycemia was higher at the end of the experiment. The parameters of inflammation and oxidative stress did not differ. Intravenous sulfide allowed reducing energy expenditure in an anesthetized large-animal model and improved the noradrenaline responsiveness during reperfusion after aortic occlusion. Investigations are warranted, hence, whether it may also protect other organs after I/R injury.
在清醒自主呼吸的小鼠中，吸入气态硫化氢（H₂S）会产生一种“类假死”的代谢状态，伴有体温过低和氧气需求降低，从而保护机体免受致命性缺氧的影响。然而，小鼠模型可能受到质疑，因为由于其较大的表面积/质量比，啮齿动物的核心体温会迅速下降。因此，我们研究了静脉注射H₂S（硫化钠，Na₂S）是否会在麻醉和机械通气的猪中诱导出类似的代谢反应。由于据报道H₂S可改善心肌缺血后的心脏功能，我们还研究了硫化物是否会影响主动脉阻断后再灌注期间去甲肾上腺素的反应性。静脉注射硫化物（0.2 mg·kg，随后以2 mg·kg·h的剂量；n = 8）或赋形剂（n = 8）2小时后，动物接受30分钟的主动脉阻断，同时使用硝酸甘油、艾司洛尔和三磷酸腺苷-5'-磷酸来维持平均动脉压（MAP）在基线的80%至120%。在再灌注期间，滴定去甲肾上腺素以保持MAP大于或等于该水平的80%。硫化物降低了心率和心输出量，但不影响每搏输出量，显著减少了维持血流动力学目标所需的去甲肾上腺素的时间和剂量，并导致核心体温下降，同时氧气摄取和二氧化碳产生减少。尽管动脉血二氧化碳分压（PCO₂）和酸碱状态相当，但在实验结束时，硫化物组的动脉血氧分压（PO₂）较低。硫化物减轻了再灌注相关的高乳酸血症，尽管在实验结束时血糖较高。炎症和氧化应激参数没有差异。静脉注射硫化物可在麻醉的大型动物模型中减少能量消耗，并改善主动脉阻断后再灌注期间去甲肾上腺素的反应性。因此，有必要研究它是否也能在缺血/再灌注损伤后保护其他器官。
