Institute of Research, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima bunkyo-ku, Tokyo 113-8510, Japan; Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Department of Thoracic Surgery, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Med. 2021 Jun 11;2(6):773-783.e5. doi: 10.1016/j.medj.2021.04.004. Epub 2021 May 14.
Several aquatic organisms such as loaches have evolved unique intestinal breathing mechanisms to survive under extensive hypoxia. To date, it is highly controversial whether such capability can be adapted in mammalian species as another site for gas exchange. Here, we report the advent of the intestinal breathing phenomenon in mammalians by exploiting EVA (enteral ventilation via anus).
Two different modes of EVA were investigated in an experimental model of respiratory failure: intra-rectal oxygen O gas ventilation (g-EVA) or liquid ventilation (l-EVA) with oxygenated perfluorocarbon. After induction of type 1 respiratory failure, we analyzed the effectiveness of g-EVA and I-EVA in mouse and pig, followed by preclinical safety analysis in rat.
Both intra-rectal O gas and oxygenated liquid delivery were shown to provide vital rescue of experimental models of respiratory failure, improving survival, behavior, and systemic O level. A rodent and porcine model study confirmed the tolerable and repeatable features of an enema-like l-EVA procedure with no major signs of complications.
EVA has proven effective in mammalians such that it oxygenated systemic circulation and ameliorated respiratory failure. Due to the proven safety of perfluorochemicals in clinics, EVA potentially provides an adjunctive means of oxygenation for patients under respiratory distress conditions.
This work is funded by the Research Program on Emerging and Re-emerging Infectious Diseases, Research Projects on COVID-19 (JP20fk0108278, 20fk0108506h0001), from the Japan Agency for Medical Research and Development (AMED), to T.T.; Strategic Promotion for Practical Application of Innovative Medical Technology, Seeds A (A145), to T.T.; and KAKENHI 19K22657, to T.C.-Y. This research is partially supported by the AMED Translational Research Program; Strategic Promotion for Practical Application of Innovative Medical Technology (TR-SPRINT), to T.C.-Y.; and AMED JP18bm0704025h0001 (Program for Technological Innovation of Regenerative Medicine), to T.T.
一些水生生物，如泥鳅，已经进化出独特的肠道呼吸机制，以在广泛缺氧的环境中生存。迄今为止，哺乳动物是否能适应这种能力，将其作为另一个气体交换部位，仍存在很大争议。在这里，我们通过肠内通气（通过肛门进行肠内通气）报告了哺乳动物中肠道呼吸现象的出现。
在呼吸衰竭的实验模型中，研究了两种不同模式的肠内通气：直肠内氧气通气（g-EVA）或含氧全氟碳液体通气（l-EVA）。在诱导 1 型呼吸衰竭后，我们分析了 g-EVA 和 I-EVA 在小鼠和猪中的有效性，然后在大鼠中进行了临床前安全性分析。
直肠内氧气和含氧液体输送都能为呼吸衰竭的实验模型提供重要的抢救，提高存活率、行为和全身氧水平。鼠类和猪类模型研究证实了类似灌肠的 l-EVA 程序具有可耐受和可重复的特点，没有出现重大并发症迹象。
EVA 已被证明在哺乳动物中是有效的，它使全身循环充氧并改善了呼吸衰竭。由于全氟化学品在临床中的安全性已得到证实，EVA 可能为呼吸窘迫患者提供一种辅助供氧手段。
这项工作得到了新发和再发传染病研究计划、COVID-19 研究项目（JP20fk0108278、20fk0108506h0001）、日本医疗研究与发展机构（AMED）的资助，用于 T.T.；战略推广创新医疗技术的实际应用，种子 A（A145），用于 T.T.；和 KAKENHI 19K22657，用于 T.C.-Y. 这项研究部分得到了 AMED 转化研究计划的支持；战略推广创新医疗技术的实际应用（TR-SPRINT），用于 T.C.-Y.；和 AMED JP18bm0704025h0001（再生医学技术创新计划），用于 T.T.
