"Every time we performed experiments, we were quite surprised," Takebe told Live Science.
没有肠道通气，miceplaced in a low-oxygen environment survived for only about 11 minutes; with ventilation into their anuses, 75% survived for 50 minutes, thanks to an infusion of oxygen that reached their hearts. The team then tried using oxygenated liquid, rather than gas, in mice, rats andpigs，他们发现了同样有前途的结果。根据他们的研究结果14在期刊上发布的研究结果，仍然需要做更多的工作，以了解这些方法是否在人类中是安全有效的。Med。
"The pandemic has highlighted the need to expand options for ventilation and oxygenation in critical illness, and this niche will persist even as the pandemic subsides," as there will be times when mechanical ventilation is unavailable or inadequate on its own, Dr. Caleb Kelly, a clinical fellow and physician-scientist at Yale School of Medicine,在研究的评论中写道。If, after further evaluation, intestinal ventilation eventually becomes common practice in intensive care units, this new study "will be marked by historians as a key scientific contribution," he wrote.
Before starting their experiments in rodents, the team got very familiar with loach guts. The fish take in oxygen mostly through their gills, but occasionally, when exposed to low-oxygen conditions, loaches instead use a portion of their intestines for gas exchange, Takebe said. In fact, in response to the lack of oxygen, the structure of gut tissues near the anus changes such that the density of nearby blood vessels increases and secretion of fluids related to digestion decreases.
These subtle changes allow loaches to "suck up the oxygen more efficiently," Takebe said. In addition, the outermost lining of the loach gut — the epithelium — is very thin, meaning oxygen can easily permeate the tissue to reach the blood vessels beneath, he added. To simulate this structure in their mouse models, the team thinned out the gut epithelium of the rodents using chemicals and various mechanical procedures.
Although this initial experiment suggested that oxygen could pass through the intestine and into循环据说，稀疏肠道上皮可能在人类患者中可能是不可行的。
Particularly in critically ill patients, "I think additional damage to the gut would be really dangerous, for the treatment perspective," Takebe said. But "over the course of the experiments, we realized that even the intact gut has some, not really efficient, but some capacity to exchange the gas," he noted, meaning there may be a way to introduce oxygen through the gut without first thinning out the tissues.
So in another experiment, rather than using oxygen gas, the team tried perfluorodecalin (PFD), a liquid fluorocarbon that can be infused with a large amount of oxygen. The liquid is already used in people, such as for use in the lungs of infants with severe respiratory distress, the authors noted in their report.
液体还可作为表面活性剂 - 降低表面张力的物质;由于表面活性剂介绍肺的气囊并有助于提高器官中的气体交换，因此PFD可以满足肠道中的类似目的。
Much like in the oxygen-gas experiments, the oxygenated PFD rescued mice from the effects of being placed in a low-oxygen chamber, enabling the rodents to meander about their cage more than mice not given the treatment. After just one injection of 0.03 ounces (1 milliliter) of the liquid, the rodents' improvements persisted for about 60 minutes.
"We are not quite sure why this improvement is persisting much longer than the original expectations," Takebe noted, as the authors expected the effects to wear off in just a couple minutes. "But the observation is really reproducible and very robust."
The team also tested the safety of repeat dosing in rats and found that, while their oxygen levels rose, the animals showed no notable side effects, markers of organ damage or stray PFD lingering in their cells.
例如，治疗可能潜在刺激迷走神经 - 一种连接肠道和脑的长神经 - 所以审判组织者可能会在副作用时享受，如血压下降或晕倒。而且，与身体中的其他器官相比，下肠含有相对较少的氧气。他说，肠道内肠道的细菌和病毒的群落适应了这些低氧条件，突然输注氧气可能会破坏这些微生物。
此外，该研究中的动物模型并不完全反映呼吸衰竭期间患者经历的危重患者的经历，这种病症通常与感染，炎症和低血流，凯利指出。因此，在啮齿动物和猪不相关的患者中可能存在额外的因素需要考虑。此外，根据给定的患者的病情，他们可能需要更高或更低剂量的PFD - 所有这些细节都需要在未来的试验中仔细评估。
Originally published on Live Science.