Lars L. Karlsson

Toxicity of lunar dust

The formation, composition and physical properties of lunar dust are incompletely characterised with regard to human health. While the physical and chemical determinants of dust toxicity for materials such as asbestos, quartz, volcanic ashes and urban particulate matter have been the focus of substantial research efforts, lunar dust properties, and therefore lunar dust toxicity may differ substantially. In this contribution, past and ongoing work on dust toxicity is reviewed, and major knowledge gaps that prevent an accurate assessment of lunar dust toxicity are identified. Finally, a range of studies using ground-based, low-gravity, and in situ measurements is recommended to address the identified knowledge gaps. Because none of the curated lunar samples exist in a pristine state that preserves the surface reactive chemical aspects thought to be present on the lunar surface, studies using this material carry with them considerable uncertainty in terms of fidelity. As a consequence, in situ data on lunar dust properties will be required to provide ground truth for ground-based studies quantifying the toxicity of dust exposure and the associated health risks during future manned lunar missions.

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.

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.

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.

Regional lung ventilation in humans during hypergravity studied with quantitative SPECT.

Recently we challenged the view that arterial desaturation during hypergravity is caused by redistribution of blood flow to dependent lung regions by demonstrating a paradoxical redistribution of blood flow towards non-dependent regions. We have now quantified regional ventilation in 10 healthy supine volunteers at normal and three times normal gravity (1G and 3G). Regional ventilation was measured with Technegas ((99m)Tc) and quantitative single photon emission computed tomography (SPECT). Hypergravity caused arterial desaturation, mean decrease 8%, p<0.05 vs. 1G. The ratio for mean ventilation per voxel for non-dependent and dependent lung regions was 0.81±0.12 during 1G and 1.63±0.35 during 3G (mean±SD), p<0.0001. Thus, regional ventilation was shifted from dependent to non-dependent regions. We suggest that arterial desaturation during hypergravity is caused by quantitatively different redistributions of blood flow and ventilation. To our knowledge, this is the first study presenting high-resolution measurements of regional ventilation in humans breathing normally during hypergravity.

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.