Oxygenation through oral Ox66 in a two-hit rodent model of respiratory distress.
Bjorn K SongDanuel A CarrBjorn K SongWilliam H NugentPublished in: Artificial cells, nanomedicine, and biotechnology (2024)
Acute respiratory distress syndrome (ARDS) is a complication of pulmonary disease that produces life-threatening hypoxaemia. Despite ventilation and hyperoxic therapies, undetected hypoxia can manifest in capillary beds leading to multi-organ failure. Ox66™ is an ingestible, solid-state form of oxygen designed to supplement oxygen deficits. Twenty-four anaesthetized rats underwent a two-hit model of respiratory distress (ARDS), where a single dose (5 mg/kg) of lipopolysaccharide (LPS) was given intratracheally, and then the respiratory tidal volume was reduced by 40%. After 60 min, animals were randomized to receive Ox66™, or normal saline (NS; vehicle control) via gavage or supplemental inspired oxygen (40% FiO 2 ). A second gavage was administered at 120 min. Cardiovascular function and blood oximetry/chemistry were measured alongside the peripheral spinotrapezius muscle's interstitial oxygenation (P ISF O 2 ). ARDS reduced mean arterial pressure (MAP) and P ISF O 2 compared to baseline (BL) for all treatment groups. Treatment with Ox66 or NS did not improve MAP, but 40% FiO 2 caused a rapid return to BL. P ISF O 2 improved after treatment with Ox66 ™ and 40% FiO 2 and remained elevated for both groups against NS until study conclusion. Both oxygen treatments also suppressed the inflammatory response to LPS, suggesting that Ox66 ™ can deliver therapeutically-impactful levels of oxygen in situations of pulmonary dysfunction.
Keyphrases
- acute respiratory distress syndrome
- mechanical ventilation
- extracorporeal membrane oxygenation
- inflammatory response
- low density lipoprotein
- pulmonary hypertension
- solid state
- dengue virus
- respiratory failure
- oxidative stress
- skeletal muscle
- randomized controlled trial
- traumatic brain injury
- clinical trial
- open label
- anti inflammatory
- intensive care unit
- double blind
- toll like receptor
- placebo controlled
- zika virus
- phase iii
- smoking cessation
- quantum dots
- lps induced