Rodents and pigs share with certain aquatic organisms the ability to use their intestines to breathe, according to a study published in the journal ‘Med’. Researchers have shown that delivery of oxygen gas or oxygenated liquid through the rectum provided vital rescue to two mammalian models with respiratory failure.
“Artificial ventilation plays a critical 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 of the University of Medical and Dental. Tokyo and Cincinnati Children’s Hospital Medical Center.
“Although 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,” he adds.
Several aquatic organisms have evolved unique intestinal respiratory mechanisms to survive in low oxygen conditions using organs other than the lungs or gills. For example, sea cucumbers, freshwater fish called loaches, and certain freshwater catfish use their intestines to breathe. But it has been much debated whether mammals have similar capabilities.
In the new study, Takebe and his colleagues provide evidence of intestinal 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 mice survived 11 minutes of extremely low oxygen conditions. With intestinal gas ventilation, more oxygen was delivered to the heart and 75% of the mice survived 50 minutes of normally lethal low-oxygen conditions.
Since the intestinal gas ventilation system requires abrasion of the intestinal mucosa, it is unlikely to be clinically viable, especially in severely ill patients, so the researchers also developed a liquid-based alternative using oxygenated perfluorochemicals. These chemicals have already been clinically proven to be biocompatible and safe in humans.
The liquid intestinal ventilation system provided therapeutic benefits to rodents and pigs exposed to non-lethal low oxygen conditions. Mice that received intestinal ventilation were able to walk further in a chamber with 10% oxygen, and more oxygen reached the heart, compared to mice that did not receive intestinal ventilation.
Similar results were obtained in pigs. The liquid intestinal ventilation reversed the paleness and coldness of the skin and increased its oxygen levels, without producing obvious side effects. Taken together, the results demonstrate that this strategy is effective in providing oxygen that reaches the circulation and alleviates the symptoms of respiratory failure in two mammalian model systems.
With the support of the Japan Medical Research and Development Agency to combat the coronavirus disease 2019 (COVID-19) pandemic, the researchers plan to expand their preclinical studies and follow regulatory steps to accelerate the path to clinical translation.
“The recent SARS-CoV-2 pandemic is overwhelming the clinical need for ventilators and artificial lungs, causing a critical shortage of available devices and putting the lives of patients around the world at risk,” says Takebe.
“The level of arterial oxygenation provided by our ventilation system, if scaled for human application, is probably sufficient to treat patients with severe respiratory failure, potentially providing life-saving oxygenation,” he adds.
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