Some aquatic organisms have evolved unique intestinal breathing mechanisms to endure deathly low-oxygen conditions, utilizing organs other than lungs or gills. For example, freshwater fish called loaches, certain freshwater catfish, and ocean cucumbers use their intestines for respiration. But it’s been unknown whether mammals have similar capabilities until now.
Researchers recently discovered that rodents and pigs share this survival capacity with aquatic organisms. The animals can use their intestines for respiration. The researchers demonstrated that the delivery of oxygenated liquid or oxygen gas through the rectum supplied vital rescue to two mammalian respiratory failure models.
Senior study author Takanori Takebe of the Cincinnati Children’s Hospital Medical Center and the Tokyo Medical and Dental University said in a press release:
Artificial respiratory support plays a vital role in the clinical management of respiratory failure due to severe illnesses such as pneumonia or acute respiratory distress syndrome. Although the side effects and safety need to be thoroughly evaluated in humans, our approach may offer a new paradigm to support critically ill patients with respiratory failure.
In the new research, Takebe and his collaborators offer evidence of abdominal breathing in mice, rats, and pigs. They did so in two separate experiments – one with oxygen gas and the other with oxygenated liquid.
First, they designed an intestinal gas system to administer pure oxygen through the rectum of mice and used it to test the animals’ ability to inhale through their anuses. This investigation revealed mice couldn’t survive beyond 11 minutes of lethally low-oxygen conditions without the system. However, with the anal ventilator, 75% of the mice survived 50 minutes in the same life-threatening conditions.
The downside of this approach is that it’s unlikely to be clinically feasible (especially in severely ill patients) because the intestinal gas ventilation system requires abrasion of the intestinal mucosa. So, the team created a liquid-based alternative made of oxygenated perfluorochemicals for the second experiment. Such chemicals have already been shown clinically to be biocompatible and safe in humans.
The intestinal liquid ventilation system provided beneficial therapeutic results to pigs and rodents exposed to non-lethal low-oxygen conditions. Mice that received the liquid-based oxygen could walk farther in a 10% oxygen chamber, with more oxygen reaching their heart, than mice that didn’t receive the ventilation. Pigs faired similar results. Furthermore, intestinal liquid ventilation reversed skin coldness and pallor and increased the animals’ oxygen levels without apparent side effects.
In conclusion, both experiments’ results reveal that this oxygen-providing strategy is effective. The oxygen in gas and liquid form reaches circulation and alleviates respiratory failure in both mammalian model systems.
With that discovered, the scientists hope their new system could be applied to humans, principally now during the pandemic, but also for people inflicted by air pollution-induced illness.
Takebe said:
The recent SARS-CoV-2 pandemic is overwhelming the clinical need for ventilators and artificial lungs, resulting in a critical shortage of available devices and endangering patients’ lives worldwide. The level of arterial oxygenation provided by our ventilation system, if scaled for human application, is likely sufficient to treat patients with severe respiratory failure, potentially providing life-saving oxygenation.
The researchers plan to elaborate on their preclinical studies and pursue regulatory actions to hasten the path to clinical translation with support from the Japan Agency for Medical Research and Development. They want to use their work to combat the coronavirus disease 2019 (COVID-19) pandemic. Of course, our respiratory is much more complex than that of a rodent or a pig, but maybe the team will find a way to make it work and save many lives!
