Tryggve E. Hemmingsson

Lower exhaled nitric oxide in hypobaric than in normobaric acute hypoxia

Analysis of exhaled nitric oxide (NO) has become an accepted complementary tool in the management of inflammatory airway diseases. Previous studies have demonstrated reduced exhaled NO at altitude and ascribed their findings to hypoxia. We studied exhaled NO partial pressures (Pe(NO)) in eight healthy subjects at reduced ambient pressure down to 540 hPa (equivalent to 5000 m altitude) and at sea level, with equivalently hypoxic breathing gases (down to 11.3% O2 in N2). Pe(NO) readings were corrected for gas density effects on the instrument performance. Sea level control values for Pe(NO) at an exhaled flow of 50 mls(-1) averaged 2.4 mPa and were virtually unchanged with normobaric hypoxia down to an inspired P(O)(2) of 10.7 kPa. With the same degree of hypoxia, hypobaric Pe(NO) was 1.4 mPa. The reduction in hypobaric Pe(NO) of up to 33+/-16% (mean+/-SD) in comparison to normobaric Pe(NO), is likely to have been caused by enhanced axial back diffusion of NO because of the reduced gas density and an associated increased alveolar NO uptake to the blood.

Measuring exhaled nitric oxide at high altitude.

The altitude performance of two NO analysers using different NO detectors was studied. The analysers and their flow regulators were tested with simulated exhalations of reference gases. At 4000 m, volume flow was +35% and mass flow -24% of nominal in both instruments. The reduced mass flow increased the exhaled NO fraction by 26% for a given rate of NO excretion. Furthermore, the electrochemical NO detector in one analyser showed an increased signal level for a given partial pressure of test gas. Taken together, these two effects increased the signal output by 60% in comparison to the NO partial pressure. To avoid the above errors, it is proposed that the flow regulator should be readjusted to give a volume flow of 50 ml s(-1) at the altitude of interest and that the analyser should be recalibrated to the operational altitude. Finally, it is recommended that exhaled NO should always be reported as partial pressure and not as volume fraction, in order to compare measurements at any altitude.

Venous gas emboli and exhaled nitric oxide with simulated and actual extravehicular activity

The decompression experienced due to the change in pressure from a space vehicle (1013hPa) to that in a suit for extravehicular activity (EVA) (386hPa) was simulated using a hypobaric chamber. Previous ground-based research has indicated around a 50% occurrence of both venous gas emboli (VGE) and symptoms of decompression illness (DCI) after similar decompressions. In contrast, no DCI symptoms have been reported from past or current space activities. Twenty subjects were studied using Doppler ultrasound to detect any VGE during decompression to 386hPa, where they remained for up to 6h. Subjects were supine to simulate weightlessness. A large number of VGE were found in one subject at rest, who had a recent arm fracture; a small number of VGE were found in another subject during provocation with calf contractions. No changes in exhaled nitric oxide were found that can be related to either simulated EVA or actual EVA (studied in a parallel study on four cosmonauts). We conclude that weightlessness appears to be protective against DCI and that exhaled NO is not likely to be useful to monitor VGE.

Microgravity decreases and hypergravity increases exhaled nitric oxide

Inhalation of toxic dust during planetary space missions may cause airway inflammation, which can be monitored with exhaled nitric oxide (NO). Gravity will differ from earth, and we hypothesized that gravity changes would influence exhaled NO by altering lung diffusing capacity and alveolar uptake of NO. Five subjects were studied during microgravity aboard the International Space Station, and 10 subjects were studied during hypergravity in a human centrifuge. Exhaled NO concentrations were measured during flows of 50 (all gravity conditions), 100, 200, and 500 ml/s (hypergravity). During microgravity, exhaled NO fell from a ground control value of 12.3 +/- 4.7 parts/billion (mean +/- SD) to 6.6 +/- 4.4 parts/billion (P = 0.016). In the centrifuge experiments and at the same flow, exhaled NO values were 16.0 +/- 4.3, 19.5 +/- 5.1, and 18.6 +/- 4.7 parts/billion at one, two, and three times normal gravity, where exhaled NO in hypergravity was significantly elevated compared with normal gravity (P <or= 0.011 for all flows). Estimated alveolar NO was 2.3 +/- 1.1 parts/billion in normal gravity and increased significantly to 3.9 +/- 1.4 and 3.8 +/- 0.8 parts/billion at two and three times normal gravity (P < 0.002). The findings of decreased exhaled NO in microgravity and increased exhaled and estimated alveolar NO values in hypergravity suggest that gravity-induced changes in alveolar-to-lung capillary gas transfer modify exhaled NO.

Effects of ambient pressure on pulmonary nitric oxide

Airway nitric oxide (NO) has been proposed to play a role in the development of high-altitude pulmonary edema. We undertook a study of the effects of acute changes of ambient pressure on exhaled and alveolar NO in the range 0.5-4 atmospheres absolute (ATA, 379-3,040 mmHg) in eight healthy subjects breathing normoxic nitrogen-oxygen mixtures. On the basis of previous work with inhalation of low-density helium-oxygen gas, we expected facilitated backdiffusion and lowered exhaled NO at 0.5 ATA and the opposite at 4 ATA. Instead, the exhaled NO partial pressure (Pe(NO)) did not differ between pressures and averaged 1.21 ± 0.16 (SE) mPa across pressures. As a consequence, exhaled NO fractions varied inversely with pressure. Alveolar estimates of the NO partial pressure differed between pressures and averaged 88 (P = 0.04) and 176 (P = 0.009) percent of control (1 ATA) at 0.5 and 4 ATA, respectively. The airway contribution to exhaled NO was reduced to 79% of control (P = 0.009) at 4 ATA. Our finding of the same Pe(NO) at 0.5 and 1 ATA is at variance with previous findings of a reduced Pe(NO) with inhalation of low-density gas at normal pressure, and this discrepancy may be due to the much longer durations of low-density gas breathing in the present study compared with previous studies with helium-oxygen breathing. The present data are compatible with the notion of an enhanced convective backtransport of NO, compensating for attenuated backdiffusion of NO with increasing pressure. An alternative interpretation is a pressure-induced suppression of NO formation in the airways.

Lung diffusing capacity for nitric oxide at lowered and raised ambient pressures

Lung diffusing capacity for NO (DLNO) was determined in eight subjects at ambient pressures of 505, 1015, and 4053hPa (379, 761 and 3040mmHg) as they breathed normoxic gases. Mean values were 116.9±11.1 (SEM), 113.4±11.1 and 99.3±10.1mlmin(-1)hPa(-1)at 505, 1015, and 4053hPa, with a 13% difference between the two higher pressures (P=0.017). The data were applied to a model with two serially coupled conductances; the gas phase (DgNO, variable with pressure), and the alveolo-capillary membrane (DmNO, constant). The data fitted the model well and we conclude that diffusive transport of NO in the peripheral lung is inversely related to gas density. At normal pressure DmNO was approximately 5% larger than DLNO, suggesting that the Dg factor then is not negligible. We also conclude that the density of the breathing gas is likely to impact the backdiffusion of naturally formed NO from conducting airways to the alveoli.