Pigs and Rodents Can Breathe By way of Their Butts

Rodents and pigs share the ability of certain aquatic organisms to use their intestines to breathe, according to a study published May 14 in the journal Med. The researchers showed that the delivery of oxygen gas or oxygen-containing liquid through the rectum provided an important salvation to two mammalian models of respiratory failure.

“Artificial respiratory assistance plays an important role in the clinical management of respiratory failure due to serious illnesses such as pneumonia or acute respiratory distress syndrome,” says lead study author Takanori Takebe (@TakebeLab) of Tokyo Medical and Dental University and Cincinnati Children’s Hospital Medical Center. “While the side effects and safety in humans require careful study, our approach may offer a new paradigm for supporting critically ill patients who have stopped breathing.”

Several aquatic organisms have developed unique intestinal respiratory mechanisms to survive in low-oxygen conditions with organs other than the lungs or gills. For example, sea cucumbers, freshwater fish called loaches, and certain freshwater catfish use their intestines to breathe. However, it has been hotly debated whether mammals have similar abilities.

In the new study, Takebe and his colleagues provide information on intestinal respiration in rats, mice and pigs. First, they developed an intestinal gas ventilation system to deliver pure oxygen through the rectum of mice. They showed that without the system, no mice survived 11 minutes of extremely low-oxygen conditions. When the intestinal gas was ventilated, more oxygen reached the heart and 75% of the mice survived 50 minutes in normally lethal, low-oxygen conditions.

Since the intestinal gas ventilation system requires abrasion of the intestinal muscles, it is clinically unlikely that this will be possible, especially in seriously ill patients. Therefore, the researchers also developed a liquid-based alternative using oxygen-containing perfluorochemicals. It has been shown clinically that these chemicals are biocompatible and safe in humans.

The intestinal fluid ventilation system offered therapeutic benefits to rodents and pigs exposed to non-fatal deoxygenated conditions. Mice that received intestinal ventilation were able to continue walking in a 10% oxygen chamber, and more oxygen reached their heart compared to mice that were not given intestinal ventilation. Similar results were found in pigs. Ventilation of the intestinal fluid reversed the pallor and coldness of the skin and increased its oxygen levels without causing any apparent side effects. Taken together, the results show that this strategy is effective in delivering oxygen that reaches the circulatory system and alleviates symptoms of respiratory failure in two mammalian model systems.

With the support of Japan’s Medical Research and Development Agency to Fight Coronavirus Disease 2019 (COVID-19) Pandemic, researchers plan to expand their preclinical studies and pursue regulatory steps to accelerate the path to clinical translation.

“The last one SARS-CoV-2 A pandemic is overwhelming the clinical need for ventilators and artificial lungs, creating a critical shortage of equipment available and putting the lives of patients worldwide at risk, “Takebe says. “The level of arterial oxygen delivery from our ventilation system, when scaled for human use, is likely to be sufficient to treat patients with severe respiratory failure and potentially provide a life-saving oxygen supply.”

Reference: “Enteral Ventilation in Mammals Improves Respiratory Failure” by Ryo Okabe, Toyofumi F. Chen-Yoshikawa, Yosuke Yoneyama, Yuhei Yokoyama, Satona Tanaka, Akihiko Yoshizawa, Wendy L. Thompson, Gokul Kannan, Eiji Kobayashi, Hiroshi Date, and Takanori Takebe May 14, 2021, Med.
DOI: 10.1016 / j.medj.2021.04.004

This work was supported by the Research Program for Emerging and Recurring Infectious Diseases, Research Projects on COVID-19 by the Japanese Agency for Medical Research and Development, and the AMED Program for Translational Research and the AMED Program for Technological Innovations in Regenerative Medicine.