Oxidative Stress Reaction to Hypobaric-Hyperoxic Civilian Flight Conditions

Abstract

Background: In military flight operations, during flights, fighter pilots constantly work under hyperoxic breathing conditions with supplemental oxygen in varying hypobaric environments. These conditions are suspected to cause oxidative stress to neuronal organ tissues. For civilian flight operations, the Federal Aviation Administration (FAA) also recommends supplemental oxygen for flying under hypobaric conditions equivalent to higher than 3048 m altitude, and has made it mandatory for conditions equivalent to more than 3657 m altitude.

Aim: We hypothesized that hypobaric-hyperoxic civilian commercial and private flight conditions with supplemental oxygen in a flight simulation in a hypobaric chamber at 2500 m and 4500 m equivalent altitude would cause significant oxidative stress in healthy individuals.

Methods: Twelve healthy, COVID-19-vaccinated (third portion of vaccination 15 months before study onset) subjects (six male, six female, mean age 35.7 years) from a larger cohort were selected to perform a 3 h flight simulation in a hypobaric chamber with increasing supplemental oxygen levels (35%, 50%, 60%, and 100% fraction of inspired oxygen, FiO₂, via venturi valve-equipped face mask), switching back and forth between simulated altitudes of 2500 m and 4500 m. Arterial blood pressure and oxygen saturation were constantly measured via radial catheter and blood samples for blood gases taken from the catheter at each altitude and oxygen level. Additional blood samples from the arterial catheter at baseline and 60% oxygen at both altitudes were centrifuged inside the chamber and the serum was frozen instantly at -21 °C for later analysis of the oxidative stress markers malondialdehyde low-density lipoprotein (M-LDL) and glutathione-peroxidase 1 (GPX1) via the ELISA test.

Results: Eleven subjects finished the study without adverse events. Whereas the partial pressure of oxygen (PO₂) levels increased in the mean with increasing oxygen levels from baseline 96.2 mm mercury (mmHg) to 160.9 mmHg at 2500 m altitude and 60% FiO₂ and 113.2 mmHg at 4500 m altitude and 60% FiO₂, there was no significant increase in both oxidative markers from baseline to 60% FiO₂ at these simulated altitudes. Some individuals had a slight increase, whereas some showed no increase at all or even a slight decrease. A moderate correlation (Pearson correlation coefficient 0.55) existed between subject age and glutathione peroxidase levels at 60% FiO₂ at 4500 m altitude.

Conclusion: Supplemental oxygen of 60% FiO₂ in a flight simulation, compared to flying in cabin pressure levels equivalent to 2500 m-4500 m altitude, does not lead to a significant increase or decrease in the oxidative stress markers M-LDL and GPX1 in the serum of arterial blood.

Keywords: flight conditions; glutathione-peroxidase; high altitude; hyperoxia; oxidative stress.

Figure 1

Study protocol time course with altitudes, supplemental oxygen levels, and blood sampling. FiO₂ = fraction of inspired oxygen, BG = blood gases, Flow = airflow of inspired oxygen, M-LDL = malondialdehyde-modified low-density lipoprotein, GPX1 = glutathione peroxidase 1, L = liter, min = minutes.

Figure 2

Arterial blood gas from radial line partial pressure level of oxygen in the single subjects at single points of measurement. PO₂ = partial pressure of oxygen in arterial blood, 35–100% = fraction of inspired oxygen through venturi valve-equipped face mask at the specific hypobaric altitude level, X-Axis: subject number.

Figure 3

Mean values of malondialdehyde-modified low-density lipoprotein (M-LDL) at baseline and at different altitudes with 60% inspired oxygen. Data are represented as mean ± SD.

Figure 4

Glutathione peroxidase values of the single subjects at the different points of measurement. GPX1 = glutathione peroxidase 1, A–L = subjects (subjects are marked with letters instead of numbers; the order is the same as in Figure 2), 1S = baseline at 322 m without supplemental oxygen, 6S = 2500 m equivalent altitude with 60% FiO₂, 7S = 4500 m equivalent altitude with 60% FiO₂.

Figure 5

Correlation point-cloud graph of glutathione peroxidase 1 (GPX) values in correlation with arterial PO₂ levels. 4500 m 60% = hypobaric pressure equivalent to 4500 m altitude and 60% FiO₂ through venturi valve-equipped face mask (correlation coefficient 0.38).