Differential sensitivity of lung and brain to sulfide exposure: A peripheral mechanism for apnea
Differential sensitivity of lung and brain to sulfide exposure: A peripheral mechanism for apnea
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DOI：
10.1093/toxsci/50.2.287
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发表时间：
1999-08-01
影响因子：
3.8
通讯作者：
Guidotti, TL
中科院分区：
文献类型：
--
作者：
Almeida, AF;Guidotti, TL
急性暴露于硫化氢 (H2S) 会导致 4 种剂量依赖性反应：呼吸过度、意识不清或昏迷、呼吸暂停和死亡。目前，这些作用的科学机制尚不清楚，但有人提出硫化物可以抑制中枢神经系统（CNS）中的细胞色素氧化酶。在这项研究中，通过比较外周和直接向大脑输送硫化物来检验以大脑为目标的前提。通过股静脉内或颈动脉内注射将NaHS给予麻醉的Sprague-Dawley雄性大鼠。以呼吸暂停为测试，外周和直接输送至大脑的ED100值分别为0.6和3.0 mg kg(-1)。外周递送的效率是直接递送至大脑的 5 倍，如果考虑相对稀释因素，则效率更高。应用于迷走神经的利多卡因可以防止呼吸暂停，因此肺脑传输至关重要。因此得出结论，肺是外周作用部位。呼吸过度的持续时间随着剂量的增加而增加。位于动脉导管远端的颈动脉体感知到高剂量的 NaHS，但并未引发呼吸暂停。静脉输注或腹腔注射 NaHCO3 可预防呼吸过度、呼吸暂停和死亡。得出以下结论：颈动脉体与 NaHS 诱导的呼吸暂停无关，肺部而不是大脑是 H2S 的主要作用部位，并且来自肺部的传入神经信号通过迷走神经诱导呼吸暂停。最后，NaHCO3 似乎可以通过某种无法解释的机制来防止硫化物的毒性，从而防止 H2S 的毒性。在现场对急性毒性进行实用的紧急治疗是可能的。
Acute exposure to hydrogen sulfide (H2S) causes 4 dose-dependent responses: hyperpnea, unconsciousness or knockdown, apnea, and death. At present, scientific mechanisms for these effects are unknown, but inhibition of cytochrome oxidase in the central nervous system (CNS) by sulfide has been suggested. In this study, the premise of brain as target is examined by comparing peripheral with direct delivery of sulfide to brain. NaHS was administered to anesthetized Sprague-Dawley male rats, by femoral intravenous, or carotid intra-arterial injection. With apnea as the test, ED100 values of 0.6 and 3.0 mg kg(-1) were found for peripheral and direct delivery to brain, respectively. Peripheral delivery is 5 times as effective as direct delivery to the brain, and greater if the relative dilution factors are considered. Lidocaine, applied to the vagus, prevented apnea, so lung-brain transmission was essential. It was therefore concluded that the lung is the peripheral site of action. Hyperpnea increased in duration with dose. The carotid body, located distal to the arterial catheter, sensed the high doses of NaHS but did not trigger apnea. Intravenous infusion or intraperitoneal injection with NaHCO3 prevented hyperpnea, apnea, and death. The following conclusions are drawn: the carotid body is not implicated in NaHS-induced apnea, the lung and not brain harbors the primary site of action of H2S, and an afferent neural signal from the lung via the vagus induces the apnea. Finally, NaHCO3 appears to prevent toxicity from sulfide, and therefore H2S, by some unexplained mechanism. Practical emergency treatment for acute toxicity in the field may be possible.