Rodents and pigs share with some aquatic organisms the ability to use their intestines for respiration, according to a study published May 14 in the journal With. The researchers demonstrated that the administration of gaseous oxygen or oxygenated liquid through the rectum offered a vital rescue to two mammalian models of respiratory failure.
“Artificial respiratory support plays an essential 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 Tokyo Medical and Dental University and Cincinnati Children’s Hospital Medical Center. “Although side effects and safety need to be carefully evaluated in humans, our approach may offer a new paradigm for supporting critically ill patients with respiratory failure.
Several aquatic organisms have developed unique gut respiration mechanisms to survive in low oxygen conditions using organs other than the lungs or gills. For example, sea cucumbers, freshwater fish called loaches, and some freshwater catfish use their intestines to breathe. But it has been debated at length whether mammals have similar abilities.
In the new study, Takebe and colleagues provide evidence for gut respiration in rats, mice, and pigs. First, they designed an intestinal gas ventilation system to deliver pure oxygen through the rectum of mice. They showed that without the system, no mouse survived 11 minutes under extremely low oxygen conditions. With gut gas ventilation, more oxygen reached the heart and 75% of the mice survived 50 minutes of normally fatal low oxygen conditions.
Since the intestinal gas ventilation system requires abrasion of the intestinal muscles, this is unlikely to be clinically feasible, especially in critically ill patients – so researchers have also developed a liquid-based alternative using oxygenated perfluorochemicals. These chemicals have already been clinically shown to be biocompatible and safe in humans.
The intestinal fluid ventilation system has provided therapeutic benefits to rodents and pigs exposed to non-lethal low oxygen conditions. Mice receiving intestinal ventilation could walk further in a 10% oxygen chamber and more oxygen reached their hearts, compared to mice that did not receive intestinal ventilation. Similar results were evident in pigs. Liquid intestinal ventilation reversed the paleness and coldness of the skin and increased their oxygen levels, without producing obvious side effects. Taken together, the results show that this strategy is effective in delivering oxygen that reaches the circulation and alleviates symptoms of respiratory failure in two model mammalian systems.
With the support of the Japan Agency for Medical Research and Development to combat the 2019 Coronavirus Disease (COVID-19) pandemic, the researchers plan to expand their preclinical studies and continue regulatory steps to accelerate the path of clinical translation.
“The recent SARS-CoV-2 pandemic is crushing the clinical need for ventilators and artificial lungs, causing a critical shortage of available devices and endangering the lives of patients around the world,” Takebe says. “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 vital oxygen.”
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