Pulmonary nitric oxide in astronauts before and during long-term spaceflight.

Introduction: During exploratory space flights astronauts risk exposure to toxic planetary dust. Exhaled nitric oxide partial pressure (PENO) is a simple method to monitor lung health by detecting airway inflammation after dust inhalation. The turnover of NO in the lungs is dependent on several factors which will be altered during planetary exploration such as gravity (G) and gas density. To investigate the impacts of these factors on normal PENO, we took measurements before and during a stay at the International Space Station, at both normal and reduced atmospheric pressures. We expected stable PENO levels during the preflight and inflight periods, with lower values inflight. With reduced pressure we expected no net changes of PENO. Material and methods: Ten astronauts were studied during the pre-flight (1 G) and inflight (µG) periods at normal pressure [1.0 ata (atmospheres absolute)], with six of them also monitored at reduced (0.7 ata) pressure and gas density. The average observation period was from 191 days before launch until 105 days after launch. PENO was measured together with estimates of alveolar NO and the airway contribution to the exhaled NO flux. Results: The levels of PENO at 50 mL/s (PENO50) were not stable during the preflight and inflight periods respectively but decreased with time (p = 0.0284) at a rate of 0.55 (0.24) [mean (SD)] mPa per 180 days throughout the observation period, so that there was a significant difference (p < 0.01, N = 10) between gravity conditions. Thus, PENO50 averaged 2.28 (0.70) mPa at 1 G and 1.65 (0.51) mPa during µG (-27%). Reduced atmospheric pressure had no net impact on PENO50 but increased the airway contribution to exhaled NO. Discussion: The time courses of PENO50 suggest an initial airway inflammation, which gradually subsided. Our previous hypothesis of an increased uptake of NO to the blood by means of an expanded gas-blood interface in µG leading to decreased PENO50 is neither supported nor contradicted by the present findings. Baseline PENO50 values for lung health monitoring in astronauts should be obtained not only on ground but also during the relevant gravity conditions and before the possibility of inhaling toxic planetary dust.

Lung diffusing capacity for nitric oxide in space: microgravity gas density interactions.

Introduction: During manned space exploration lung health is threatened by toxic planetary dust and radiation. Thus, tests such as lung diffusing capacity (DL) are likely be used in planetary habitats to monitor lung health. During a DL maneuver the rate of uptake of an inspired blood-soluble gas such as nitric oxide (NO) is determined (DLNO). The aim of this study was to investigate the influence of altered gravity and reduced atmospheric pressure on the test results, since the atmospheric pressure in a habitat on the moon or on Mars is planned to be lower than on Earth. Changes of gravity are known to alter the blood filling of the lungs which in turn may modify the rate of gas uptake into the blood, and changes of atmospheric pressure may alter the speed of gas transport in the gas phase. Methods: DLNO was determined in 11 subjects on the ground and in microgravity on the International Space Station. Experiments were performed at both normal (1.0 atm absolute, ata) and reduced (0.7 ata) atmospheric pressures. Results: On the ground, DLNO did not differ between pressures, but in microgravity DLNO was increased by 9.8% (9.5) (mean [SD]) and 18.3% (15.8) at 1.0 and 0.7 ata respectively, compared to normal gravity, 1.0 ata. There was a significant interaction between pressure and gravity (p = 0.0135). Discussion: Estimates of the membrane (DmNO) and gas phase (DgNO) components of DLNO suggested that at normal gravity a reduced pressure led to opposing effects in convective and diffusive transport in the gas phase, with no net effect of pressure. In contrast, a DLNO increase with reduced pressure at microgravity is compatible with a substantial increase of DmNO partially offset by reduced DgNO, the latter being compatible with interstitial edema. In microgravity therefore, DmNO would be proportionally underestimated from DLNO. We also conclude that normal values for DL in anticipation of planetary exploration should be determined not only on the ground but also at the gravity and pressure conditions of a future planetary habitat.

Effects of an artificial gravity countermeasure on orthostatic tolerance, blood volumes and aerobic power after short-term bed rest (BR-AG1).

Exposure to artificial gravity (AG) in a short-arm centrifuge has potential benefits for maintaining human performance during long-term space missions. Eleven subjects were investigated during three campaigns of 5 days head-down bed rest: 1) bed rest without countermeasures (control), 2) bed rest and 30 min of AG (AG1) daily, and 3) bed rest and six periods of 5 min AG (AG2) daily. During centrifugation, the supine subjects were exposed to AG in the head-to-feet direction with 1 G at the center of mass. Subjects participated in the three campaigns in random order. The cardiovascular effects of bed rest and countermeasures were determined from changes in tolerance to a head-up tilt test with superimposed lower body negative pressure (HUT), from changes in plasma volume (PV) and from changes in maximum aerobic power (V̇o2 peak) during upright work on a cycle ergometer. Complete data sets were obtained in eight subjects. After bed rest, HUT tolerance times were 36, 64, and 78% of pre-bed rest baseline during control, AG1 and AG2, respectively, with a significant difference between AG2 and control. PV and V̇o2 peak decreased to 85 and 95% of pre-bed rest baseline, respectively, with no differences between the treatments. It was concluded that the AG2 countermeasure should be further investigated during future long-term bed rest studies, especially as it was better tolerated than AG1. The superior effect of AG2 on orthostatic tolerance could not be related to concomitant changes in PV or aerobic power.

No protective role for hypoxic pulmonary vasoconstriction in severe hypergravity-induced arterial hypoxemia.

Supine subjects exposed to hypergravity show a marked arterial desaturation. Previous work from our laboratory has also shown a paradoxical reduction of lung perfusion in dependent lung regions in supine subjects exposed to hypergravity. We reasoned that the increased lung weight during hypergravity caused either direct compression of the blood vessels in the dependent lung tissue or that poor regional ventilation caused reduced perfusion through hypoxic pulmonary vasoconstriction (HPV). The objective of this study was to evaluate the importance of HPV through measurements of arterial oxygenation during exposure to hypergravity with normal and attenuated HPV. A further increased arterial desaturation during hypergravity with attenuated HPV would support the hypothesis that HPV contributes to the paradoxical redistribution of regional perfusion. In a two-phased randomized study we first exposed 12 healthy subjects to 5 G while supine during two single-blinded conditions; control and after 50 mg sildenafil p.o.. In a second phase, 12 supine subjects were exposed to 5 G during three single-blinded conditions; control, after 100 mg sildenafil p.o. and after inhalation of 10 µg iloprost. There was a substantial arterial desaturation by 5-30% units in all subjects with no or only minor differences between conditions. The results speak against HPV as a principal mechanism for the hypergravity-induced reduction of lung perfusion in dependent lung regions in supine humans.

Effect of blood redistribution on exhaled and alveolar nitric oxide: a hypergravity model study.

Alveolar (CA(NO)) and exhaled nitric oxide (FE(NO)) concentrations, mainly regarded as inflammation surrogates, may also be affected by perfusion redistribution changing alveolar transfer factor (DA(NO)). A model of blood redistribution is hypergravity, Karlsson et al. (2009b) found, at 2G, increases of 22% and 70%, for FE(NO), and CA(NO), respectively. The present study aimed at theoretically estimating the amplitude of DA(NO) changes that mimic these experimental data. An equation describing convection, diffusion and NO sources was solved in a 2-trumpet model (parallel dependent and non-dependent lung units). Acinar airways lumen reduction was also simulated. A reduction of 33% of the overall DA(NO) (-51% in the non-dependent unit) along with a 36% reduction of acinar airways lumen reproduced experimental findings. In conclusion, substantial FE(NO) and CA(NO) increases may be accounted for by a decrease of the alveolo-capillaries contact surface, here hypergravity-induced. Acinar airway constriction may also have a part in the overall FE(NO) increase.

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

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.

Central command and metaboreflex cardiovascular responses to sustained handgrip during microgravity.

Four subjects were studied before and during a 16-day space flight. The test included 2min of rest, 2min of sustained handgrip (SHG), and 2min of post-exercise circulatory occlusion (PECO). Heart rate (HR) and mean arterial pressure (MAP) responses to central command and mechanoreceptor stimulation were determined from the difference between SHG and PECO. Responses to metaboreceptor stimulation were determined from the difference between PECO and rest. Late in-flight (days 12-14) the central command/mechanoreceptor component of the HR response was reduced by 5bpm (P=0.01) from its pre-flight value of 15 (+/-3)bpm (mean (+/-SEM)). At the same time the metaboreflex responses of HR and MAP were unchanged. The attenuated HR response to central command was likely of baroreflex origin. Together with a parallel study of PECO after dynamic leg exercise, our data indicate that central processing of metaboreflex inputs is unchanged in microgravity whereas metaboreflex inputs from weight-bearing muscles are enhanced.