Exposure to Non-Steady-State Oxygen Is Reflected in Changes to Arterial Blood Gas Values, Prefrontal Cortical Activity, and Systemic Cytokine Levels.

Onboard oxygen-generating systems (OBOGSs) provide increased inspired oxygen (FiO2) to mitigate the risk of neurologic injury in high altitude aviators. OBOGSs can deliver highly variable oxygen concentrations oscillating around a predetermined FiO2 set point, even when the aircraft cabin altitude is relatively stable. Steady-state exposure to 100% FiO2 evokes neurovascular vasoconstriction, diminished cerebral perfusion, and altered electroencephalographic activity. Whether non-steady-state FiO2 exposure leads to similar outcomes is unknown. This study characterized the physiologic responses to steady-state and non-steady-state FiO2 during normobaric and hypobaric environmental pressures emulating cockpit pressures within tactical aircraft. The participants received an indwelling radial arterial catheter while exposed to steady-state or non-steady-state FiO2 levels oscillating ± 15% of prescribed set points in a hypobaric chamber. Steady-state exposure to 21% FiO2 during normobaria produced arterial blood gas values within the anticipated ranges. Exposure to non-steady-state FiO2 led to PaO2 levels higher upon cessation of non-steady-state FiO2 than when measured during steady-state exposure. This pattern was consistent across all FiO2 ranges, at each barometric condition. Prefrontal cortical activation during cognitive testing was lower following exposure to non-steady-state FiO2 >50% and <100% during both normobaria and hypobaria of 494 mmHg. The serum analyte levels (IL-6, IP-10, MCP-1, MDC, IL-15, and VEGF-D) increased 48 h following the exposures. We found non-steady-state FiO2 levels >50% reduced prefrontal cortical brain activation during the cognitive challenge, consistent with an evoked pattern of neurovascular constriction and dilation.

Brainstem Damage Underlies Changes in Hypoxic Ventilatory Response Following Cardiac Arrest and Resuscitation in Rats.

People resuscitated after sudden cardiac arrest remain at high risk for mortality, with treatment for survivors varying from monitoring to life support. With respect to assessing survivability post cardiac arrest and resuscitation (CAR), we previously demonstrated the potential of the hypoxic ventilatory response (HVR) as a reliable indicator for discerning between survivors and non-survivors in the early stages of recovery following CAR in rats. Since HVR describes the increase in ventilation in response to hypoxia, we hypothesize that damage to cardiorespiratory regulatory centers in the brainstem underlie the loss of HVR observed post resuscitation in nonsurvivors. Wistar rats underwent cardiac arrest (12-min) and resuscitation. At 1 day post-resuscitation, rats were perfused transcardially and the brains were harvested and processed for immunohistostaining of caspase-3, a marker of apoptosis. Positive caspase-3 staining was observed in brainstem regions such as the rostral ventral lateral medulla (RVLM); Co-localization of caspase-3 and NeuN was observed in the RVLM as well, suggesting that apoptosis most likely occurs in neurons. Our results showed positive markers for neuronal apoptosis present in pathways of the brainstem involved in respiratory and cerebrovascular regulation, suggesting brain stem damage underlies changes in HVR following CAR.

Increased Serum Levels of Proinflammatory Cytokines Are Accompanied by Fatigue in Military T-6A Texan II Instructor Pilots.

Tactical aviation imposes unprecedented physical challenges including repetitive exposure to hypergravity, hyperoxia, increased work of breathing, and profound cognitive workloads. Each stressor evokes outcomes ranging from musculoskeletal duress and atelectasis to physical and cognitive fatigue, the latter among the foremost threats to aviators. Whereas sleep loss is traditionally considered the primary cause of fatigue in aviators, converging experimental, observational, and medical studies have identified biochemical mechanisms promoting onset of fatigue. Those mechanisms, which fundamentally differ from sleep loss, revolve around increased proinflammatory cytokines, produced and released in response to tissue injury, chronic inflammatory disorders, allergens, or physical duress. This study's objective was to inform our understanding of potential relationships between serum levels of proinflammatory cytokines and onset of fatigue within a cohort of aviators who experience multiple high-performance sorties on a daily basis. Methods: Active duty and reservist T-6A Texan II instructor pilots were studied on three separate days across their week-long flying schedule. Data collected included a physical assessment, subjective fatigue levels, venous blood samples for measures of chemistry and serum analytes, and urine samples for specific gravity. Results: Twenty-three persons were studied, of which 22 fulfilled minimum study requirements of completing two sorties. The study cohort was comprised of primarily males, age 37.95 ± 4.73 years with a BMI of 26.63 ± 3.15 kg/m2. Of 37 measurable serum analytes, 20 differed significantly (p < 0.05) between baseline values with those measured at the study endpoint. Thirteen of the aviators reported increased fatigue scores across their flying schedule whereas nine did not. Eleven blood serum analytes were associated with increasing levels of fatigue. Discussion: Fatigue in aviators has been attributed almost solely to sleep loss, nocturnal sorties, or disrupted circadian rhythmicity. In contrast, our study findings suggest an alternative mechanism that can promote onset of fatigue: increased blood levels of proinflammatory cytokines. Specific mechanisms triggering synthesis and release of those cytokines and other analytes are yet to be determined. However, their expression patterns suggest responses to both chronic and acute inflammation, hyperoxia, or bronchopulmonary responses to inspiration of dry gas, positive airway pressure, or perhaps atelectasis.

Neurovascular and cortical responses to hyperoxia: enhanced cognition and electroencephalographic activity despite reduced perfusion.

KEY POINTS: Extreme aviation is accompanied by ever-present risks of hypobaric hypoxia and decompression sickness. Neuroprotection against those hazards is conferred through fractional inspired oxygen ( FI,O2 ) concentrations of 60-100% (hyperoxia). Hyperoxia reduces global cerebral perfusion (gCBF), increases reactive oxygen species within the brain and leads to cell death within the hippocampus. However, an understanding of hyperoxia's effect on cortical activity and concomitant levels of cognitive performance is lacking. This limits our understanding of whether hyperoxia could lower the brain's threshold of tolerance to physiological stressors inherent to extreme aviation, such as high gravitational forces. This study aimed to quantify the impact of hyperoxia upon global cerebral perfusion (gCBF), cognitive performance and cortical electroencephalography (EEG). Hyperoxia evoked a rapid reduction in gCBF, yet cognitive performance and vigilance were enhanced. EEG measurements revealed enhanced alpha power, suggesting less desynchrony, within the cortical temporal regions. Collectively, this work suggests hyperoxia-induced brain hypoperfusion is accompanied by enhanced cognitive processing and cortical arousal. ABSTRACT: Extreme aviators continually inspire hyperoxic gas to mitigate risk of hypoxia and decompression injury. This neuroprotection carries a physiological cost: reduced cerebral perfusion (CBF). As reduced CBF may increase vulnerability to ever-present physiological challenges during extreme aviation, we defined the magnitude and duration of hyperoxia-induced changes in CBF, cortical electrical activity and cognition in 30 healthy males and females. Magnetic resonance imaging with pulsed arterial spin labelling provided serial measurements of global CBF (gCBF), first during exposure to 21% inspired oxygen ( FI,O2 ) followed by a 30-min exposure to 100% FI,O2 . High-density EEG facilitated characterization of cortical activity during assessment of cognitive performance, also measured during exposure to 21% and 100% FI,O2 . Acid-base physiology was measured with arterial blood gases. We found that exposure to 100% FI,O2 reduced gCBF to 63% of baseline values across all participants. Cognitive performance testing at 21% FI,O2 was accompanied by increased theta and beta power with decreased alpha power across multiple cortical areas. During cognitive testing at 100% FI,O2 , alpha activity was less desynchronized within the temporal regions than at 21% FI,O2 . The collective hyperoxia-induced changes in gCBF, cognitive performance and EEG were similar across observed partial pressures of arterial oxygen ( PaO2 ), which ranged between 276-548 mmHg, and partial pressures of arterial carbon dioxide ( PaCO2 ), which ranged between 34-50 mmHg. Sex did not influence gCBF response to 100% FI,O2 . Our findings suggest hyperoxia-induced reductions in gCBF evoke enhanced levels of cortical arousal and cognitive processing, similar to those occurring during a perceived threat.