Pharmacokinetics of a single inhalation of hydrogen gas in pigs
Pharmacokinetics of a single inhalation of hydrogen gas in pigs
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DOI：
10.1371/journal.pone.0234626
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发表时间：
2020-06-19
期刊：
影响因子：
3.7
通讯作者：
Kobayashi, Eiji
中科院分区：
文献类型：
--
作者：
Sano, Motoaki;Ichihara, Genki;Kobayashi, Eiji
吸入氢气(H-2)的益处已被广泛报道，但其药代动力学尚未得到充分分析。我们在猪身上开发了一种新的实验系统，以密切评估H(2)在肺中被吸收，进入血液，并被分布、代谢和排泄的过程。我们将导管插入并固定到颈动脉(CA)、门静脉(PV)和肝上下腔静脉(IVC)，以允许重复采血，并进行双侧开胸以塌陷肺。然后，使用吸氢合金罐，我们用100%H-2填充肺部至最大吸气水平。这只猪被维持了30秒，没有恢复呼吸，就像他们屏住呼吸一样。分别于0、3、10、30、60分钟采血，用气相色谱法测定氢气浓度。H(2)浓度在屏气后即刻达到峰值，3min后降至峰值的1/40。肺静脉和下腔静脉的H(2)峰浓度分别是CA的40%和14%。但在PV和IVC(半衰期分别为310 S和350 S)中，H(2)浓度的衰减要慢于CA(半衰期：92 S)。10min时，静脉血中H(2)浓度显著高于动脉血中的浓度。60min时，门静脉血中H(2)浓度比稳态高6.9~53nL/m L，SVC比稳态高14~29nL/m L。相反，CA中的H(2)浓度下降到稳态水平。这是首次报道吸入的H(2)通过平流扩散输送到全身并动态代谢。
The benefits of inhaling hydrogen gas (H-2) have been widely reported but its pharmacokinetics have not yet been sufficiently analyzed. We developed a new experimental system in pigs to closely evaluate the process by which H(2)is absorbed in the lungs, enters the bloodstream, and is distributed, metabolized, and excreted. We inserted and secured catheters into the carotid artery (CA), portal vein (PV), and supra-hepatic inferior vena cava (IVC) to allow repeated blood sampling and performed bilateral thoracotomy to collapse the lungs. Then, using a hydrogen-absorbing alloy canister, we filled the lungs to the maximum inspiratory level with 100% H-2. The pig was maintained for 30 seconds without resuming breathing, as if they were holding their breath. We collected blood from the three intravascular catheters after 0, 3, 10, 30, and 60 minutes and measured H(2)concentration by gas chromatography. H(2)concentration in the CA peaked immediately after breath holding; 3 min later, it dropped to 1/40 of the peak value. Peak H(2)concentrations in the PV and IVC were 40% and 14% of that in the CA, respectively. However, H(2)concentration decay in the PV and IVC (half-life: 310 s and 350 s, respectively) was slower than in the CA (half-life: 92 s). At 10 min, H(2)concentration was significantly higher in venous blood than in arterial blood. At 60 min, H(2)was detected in the portal blood at a concentration of 6.9-53 nL/mL higher than at steady state, and in the SVC 14-29 nL/mL higher than at steady state. In contrast, H(2)concentration in the CA decreased to steady state levels. This is the first report showing that inhaled H(2)is transported to the whole body by advection diffusion and metabolized dynamically.