High-dose hydroxocobalamin administered after H2S exposure counteracts sulfide-poisoning-induced cardiac depression in sheep.
High-dose hydroxocobalamin administered after H2S exposure counteracts sulfide-poisoning-induced cardiac depression in sheep.
复制标题
DOI：
10.3109/15563650.2014.990976
复制
发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Sonobe T
中科院分区：
文献类型：
--
作者：
Haouzi P;Chenuel B;Sonobe T
严重的硫化氢中毒导致呼吸和心脏骤停死亡，后者可在几秒钟或几分钟内以严重中毒的形式发生。确定硫化氢诱导的心脏骤停的时程和性质，以及硫化物暴露结束后大剂量羟钴胺的影响。在16只镇静的机械通风绵羊中，在停止接触硫化氢后的几分钟内，注入NaHS以达到我们之前发现的导致心脏骤停的血液中的硫化氢浓度。停止注射NaHS后1min，静脉注射大剂量羟钴胺(5g)或生理盐水。停止接触硫化氢时，所有动物都还活着。三只动物(18%)在90秒内出现心脏骤停，无法接受任何解毒剂或药物。在存活足够长时间以接受羟钴胺或生理盐水的动物中，对照组中71%(5/7)的动物在10分钟内死于心脏骤停。在所有情况下，心脏骤停都是无脉搏电活动(PEA)的结果。在接受解毒剂的组中，静脉注射5g羟钴胺引起血压和血流量突然增加；PEA在所有情况下都得到了预防。然而，在接受羟钴胺组中，我们没有发现任何氧化代谢恢复的证据，因为尽管血液动力学恢复，但血乳酸仍然保持升高，甚至在一小时后继续上升。这与硫化氢动力学的不变恢复一起表明，羟钴胺并不是通过捕捉硫化氢的机制起作用的。在这个绵羊模型中，根据PEA，心脏骤停的风险很高，在接触硫化氢后持续10分钟。在停止硫化氢暴露后很早就注射非常大剂量的羟钴胺(5g)，可改善心肌收缩能力，防止PEA。
Severe H2S poisoning leads to death by rapid respiratory and cardiac arrest, the latter can occur within seconds or minutes in severe forms of intoxication. Determine the time course and the nature of H2S induced cardiac arrest and the effects of high dose Hydroxocobalamin administered after the end of sulfide exposure. In 16 sedated mechanically ventilated sheep, NaHS was infused to reach concentrations of H2S in the blood we previously found to lead to cardiac arrest within minutes following the cessation of H2S exposure. High dose Hydroxocobalamin (5 g) or saline solution was administered intravenously, one minute after the cessation of NaHS infusion. All animals were still alive at the cessation of H2S exposure. Three animals (18%) presented a cardiac arrest within 90 seconds and were unable to receive any antidote or vehicle. In the animals that survived long enough to receive either Hydroxocobalamin or saline, 71% (5/7) died in the control group by cardiac arrest within 10 minutes. In all instances, cardiac arrest was the result of a pulseless electrical activity (PEA). In the group that received the antidote, intravenous injection of 5 g Hydroxocobalamin provoked an abrupt increase in blood pressure and blood flow; PEA was prevented in all instances. However, we could not find any evidence for a recovery in oxidative metabolism in the group receiving Hydroxocobalamin, as blood lactate remained elevated and even continued to rise after one hour, despite restored hemodynamics. This, along with an unaltered recovery of H2S kinetics, suggests that Hydroxocobalamin did not act through a mechanism of H2S trapping. In this sheep model, there was a high risk for cardiac arrest, by PEA, persisting up to 10 minutes after H2S exposure. Very high dose of Hydroxocobalamin (5 g), injected very early after the cessation of H2S exposure, improved cardiac contractility and prevented PEA.