We evaluated their circadian rhythms using data from electrocardiographic records and examined the change in circadian period related to normal RR intervals for astronauts who completed a long-term (≥6-month) mission in space. The examinees were seven astronauts, 5 men and 2 women, from 2009 to 2010. Their mean±SD age was 52.0±4.2 years (47-59 yr). Each stayed in space for more than 160 days; their average length of stay was 172.6±14.6 days (163-199 days).We conducted 24-hr Holter electrocardiography before launch (Pre), at one month after launch (DF1), at two months after launch (DF2), at two weeks before return (DF3), and at three months astronauts, whereas it decreased in 3 of 7 astronauts and 1 was remained almost unchanged at DF1.During DF3, about 6 months after their stay in space, the HF component of 5 of 7 astronauts recovered from the decrease after launch, with prominent improvement to over 20% in 3 astronauts. 2Although autonomic nervous functions and circadian rhythms were disturbed until one month had passed in space, well-scheduled sleep and wake rhythms and meal times served as synchronizers.

The fractal scaling of the long-term heart rate variability (HRV) reflects the ‘intrinsic’ autonomic regulatory system. Herein, we examine how microgravity on the ISS affected the power-law scaling β (beta) of astronauts during a long-duration (about 6 months) spaceflight. Ambulatory electrocardiographic (ECG) monitoring was performed on seven healthy astronauts (5 men, 52.0±4.2 years of age) five times: before launch, 24±5 (F01) and 73±5 (F02) days after launch, 15±5 days before return (F03), and after return to Earth. The power-law scaling β was calculated as the slope of the regression line of the power density of the MEM spectrum versus frequency plotted on a log10–log10 scale in the range of 0.0001–0.01 Hz (corresponding to periods of 2.8 h to 1.6 min). β was less negative in space (−0.949±0.061) than on Earth (−1.163±0.075; P<0.025). The difference was more pronounced during the awake than during the rest/sleep span. The circadian amplitude and acrophase (phase of maximum) of β did not differ in space as compared with Earth. An effect of microgravity was detected within 1 month (F01) in space and continued throughout the spaceflight. The intrinsic autonomic regulatory system that protects life under serious environmental conditions on Earth is altered in the microgravity environment, with no change over the 6-month spaceflight. It is thus important to find a way to improve conditions in space and/or in terms of human physiology, not to compromise the intrinsic autonomic regulatory system now that plans are being made to inhabit another planet in the near future.

It is critical that the regulatory system functions well in space’s microgravity. However, the “intrinsic” cardiovascular regulatory system (β), estimated by the fractal scaling of heart rate variability (HRV) (0.0001–0.01 Hz), does not adapt to the space environment during long-duration (6-month) space flights. Neuroimaging studies suggest that the default mode network (DMN) serves a broad adaptive purpose, its topology changing over time in association with different brain states of adaptive behavior. Hypothesizing that HRV varies in concert with changes in brain’s functional connectivity, we analyzed 24-hour HRV records from 8 healthy astronauts (51.8 ± 3.7 years; 6 men) on long (174.5 ± 13.8 days) space missions, obtained before launch, after about 21 (ISS01), 73 (ISS02), and 156 (ISS03) days in space, and after return to Earth. Spectral power in 8 frequency regions reflecting activity in different brain regions was computed by maximal entropy. Improved β (p < 0.05) found in 4 astronauts with a positive activation in the “HRV slow-frequency oscillation” (0.10–0.20 Hz) occurred even in the absence of consciousness. The adaptive response was stronger in the evening and early sleep compared to morning (p = 0.039). Brain functional networks, the DMN in particular, can help adapt to microgravity in space with help from the circadian clock.

SummaryBackgroundSpaceflight alters human cardiovascular dynamics. The less negative slope of the fractal scaling of heart rate variability (HRV) of astronauts exposed long-term to microgravity reflects cardiovascular deconditioning. We here focus on specific frequency regions of HRV.MethodsTen healthy astronauts (8 men, 49.1 ± 4.2 years) provided five 24-hour electrocardiographic (ECG) records: before launch, 20.8 ± 2.9 (ISS01), 72.5 ± 3.9 (ISS02) and 152.8 ± 16.1 (ISS03) days after launch, and after return to Earth. HRV endpoints, determined from normal-to-normal (NN) intervals in 180-min intervals progressively displaced by 5 min, were compared in space versus Earth. They were fitted with a model including 4 major anticipated components with periods of 24 (circadian), 12 (circasemidian), 8 (circaoctohoran), and 1.5 (Basic Rest-Activity Cycle; BRAC) hours.FindingsThe 24-, 12-, and 8-hour components of HRV persisted during long-term spaceflight. The 90-min amplitude became about three times larger in space (ISS03) than on Earth, notably in a subgroup of 7 astronauts who presented with a different HRV profile before flight. The total spectral power (TF; p < 0.05) and that in the ultra-low frequency range (ULF, 0.0001–0.003 Hz; p < 0.01) increased from 154.9 ± 105.0 and 117.9 ± 57.5 msec2 (before flight) to 532.7 ± 301.3 and 442.4 ± 202.9 msec2 (ISS03), respectively. The power-law fractal scaling β was altered in space, changing from -1.087 ± 0.130 (before flight) to -0.977 ± 0.098 (ISS01), -0.910 ± 0.130 (ISS02), and -0.924 ± 0.095 (ISS03) (invariably p < 0.05).InterpretationMost HRV changes observed in space relate to a frequency window centered around one cycle in about 90 min. Since the BRAC component is amplified in space for only specific HRV endpoints, it is likely to represent a physiologic response rather than an artifact from the International Space Station (ISS) orbit. If so, it may offer a way to help adaptation to microgravity during long-duration spaceflight.

Nicotinamide (500 or 250 mg/kg body wt) or niacin (100 or 50 mg/kg body wt) was administered to hamsters given an intratracheal injection of bleomycin (BLM). At 7 days after the BLM injection, when compared with BLM-control animals, both nicotinamide- and niacin-treated animals showed similar acute lung injury, recognized as increases in the wet-to-dry lung weight ratio, intraalveolar albumin concentration, inflammatory cell number, and elastase activity. At 30 days after the BLM injection, both nicotinamide and niacin attenuated the development of pulmonary fibrosis, as indicated by fewer fibrotic changes and a decreased amount of lung hydroxyproline. Histologic examination revealed that, compared with nicotinamide, niacin had more potent antifibrotic effects. Lung nicotinamide-adenine-dinucleotide (NAD) was less depleted in nicotinamide-treated animals than in BLM-control animals. Nicotinamide- and niacin-treated animals had more intraalveolar cells than the BLM-control animals. These findings suggest that the development of pulmonary fibrosis induced by BLM was prevented through maintaining NAD by the administration of nicotinamide or niacin. Since neither nicotinamide nor niacin attenuated the inflammatory response to acute lung injury, the amelioration of fibrosis by these treatments appears to be independent of the early events.