Applied Physiology of CNS Oxygen Toxicity: Mechanisms in Humans
Abstract
Central nervous system (CNS) oxygen toxicity causes seizures. Although oxygen induced seizures are usually self-limited and requireno pharmacologic interventions during hyperbaric oxygen therapy, this same phenomena in divers underwater would likely prove fatal due to loss of regulator and drowning. As such, factors influencing CNS oxygen toxicity must be understood and optimized for diver safety and mission success. Factors that are known to increase the risk of CNS oxygen toxicity include the following: immersion in water, exercise, cold and high levels of carbon dioxide in the blood (hypercapnia),which can also affect cognition.While the influence of hypercapnia on CNS oxygen toxicity susceptibility is understood to be due to dilation of blood vessels in the brain and increased oxygen delivery, the mechanisms of the other factors are not understood. The risk of CNS oxygen toxicity is therefore dependent on the interaction among several factors: PaO2, exercise, immersion, blood pressure and PaCO2. This proposal aims to investigate these mechanisms as well as other factors that may alter susceptibility, including sleep deprivation and commonly used medications (caffeine and methylphenidate). The main end-points for all studies proposed in this application will include arterial PCO2 during submersed exercise at 98 fsw and drive to breathe: the measured increase in breathing during a progressive rise in carbon dioxide (hypercapnic ventilatory response, HCVR) and assessment of brain oxygenation using a device that measures the blood oxygenation within the skull using lasers (functional near-infrared spectroscopy, fNIRS). Studies will assess mechanisms of the effect of respiratory muscletraining (RMT) to increase ventilatory drive, including changes in hormones leptin and adiponectin and epigenetic effects. Studies will also assess the effect of sleep deprivation and possible mitigating medications that include caffeine and methylphenidate, and the effect of prolonged atmospheric CO2 exposure that could occur during transport of a diver in a submarine by administration of sodium bicarbonate. The mechanisms by which immersion and cold affect CNS oxygen toxicity is unknown. In this study the influence of blood pressure on brain oxygenation will be tested in cold and warm water.This study will provide insights into the mechanisms that influence susceptibility to CNS oxygen toxicity, including ventilatory control and its effect on arterial PCO2 during exertion in divers. The studies will further investigate mechanisms by which ventilatory control is affected by RMT (currently being studied in ourlab) and sleep deprivation (likely to occur during missions). Further, systematic study of mitigation measures will include pre-dive administration of caffeine and methylphenidate. The aim of the proposed experiments is to decrease the risks for divers of oxygen toxicity and impaired cognition induced by elevated arterial PCO2.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Sep 11, 2023
- Source ID
- N000142312830
Entities
People
- Derek Covington
Organizations
- Duke University
- Office of Naval Research
- United States Navy