Highlights
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Enteral ventilation (EVA) enabled systemic oxygenation in mammalians
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EVA improved survival and behaviors in pre-clinical models of respiratory failure
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EVA yielded no major signs of complications in pre-clinical models
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EVA may serve as a transformative approach in respiratory failure patients
Context and significance
The SARS-CoV-2 pandemic has overwhelmed the clinical need for ventilators and artificial lungs, resulting in a critical shortage of available devices and endangering patients’ lives worldwide. Inspired by organisms such as loaches that use intestinal air breathing, we show the effectiveness of an enteral ventilation approach in attaining systemic oxygenation in both rodent and porcine models. Intra-rectal delivery of a liquid form of O2 known as conjugated perfluorocarbon, a compound historically used in clinics for liquid ventilation through airway administration, is highly tolerable and efficacious in ameliorating severe respiratory failure. Thus, by repurposing the distal gut as an accessary breathing organ, enteral ventilation therapy offers an alternative paradigm as an adjunctive means to patients who are in critical need of respiratory support.
Summary
Background
Several aquatic organisms such as loaches have evolved unique intestinal breathing mechanisms to survive under extensive hypoxia. To date, it is highly controversial whether such capability can be adapted in mammalian species as another site for gas exchange. Here, we report the advent of the intestinal breathing phenomenon in mammalians by exploiting EVA (enteral ventilation via anus).
Methods
Two different modes of EVA were investigated in an experimental model of respiratory failure: intra-rectal oxygen O2 gas ventilation (g-EVA) or liquid ventilation (l-EVA) with oxygenated perfluorocarbon. After induction of type 1 respiratory failure, we analyzed the effectiveness of g-EVA and I-EVA in mouse and pig, followed by preclinical safety analysis in rat.
Findings
Both intra-rectal O2 gas and oxygenated liquid delivery were shown to provide vital rescue of experimental models of respiratory failure, improving survival, behavior, and systemic O2 level. A rodent and porcine model study confirmed the tolerable and repeatable features of an enema-like l-EVA procedure with no major signs of complications.
Conclusions
EVA has proven effective in mammalians such that it oxygenated systemic circulation and ameliorated respiratory failure. Due to the proven safety of perfluorochemicals in clinics, EVA potentially provides an adjunctive means of oxygenation for patients under respiratory distress conditions.
Funding
This work is funded by the Research Program on Emerging and Re-emerging Infectious Diseases, Research Projects on COVID-19 (JP20fk0108278, 20fk0108506h0001), from the Japan Agency for Medical Research and Development (AMED), to T.T.; Strategic Promotion for Practical Application of Innovative Medical Technology, Seeds A (A145), to T.T.; and KAKENHI 19K22657, to T.C.-Y. This research is partially supported by the AMED Translational Research Program; Strategic Promotion for Practical Application of Innovative Medical Technology (TR-SPRINT), to T.C.-Y.; and AMED JP18bm0704025h0001 (Program for Technological Innovation of Regenerative Medicine), to T.T.
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