Research Containing: Microgravity

Effect of simulated weightlessness on osteoprogenitor cell number and proliferation in young and adult rats

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Experiments with rats flown in space or hind limb unloaded (HU) indicate that bone loss in both conditions is associated with a decrease in bone volume and osteoblast surface in cancellous and cortical bone. We hypothesize that the decrease in osteoblastic bone formation and osteoblast surface is related to a decrease in the number of osteoprogenitors and/or decreased proliferation of their progeny. We tested this hypothesis by evaluating the effect of 14 days of HU on the number of osteoprogenitors (osteoblast colony forming units; CFU-O), fibroblastic colony forming units (CFU-F), and alkaline phosphatase-positive CFU (CFU-AP) in cell populations derived from the proximal femur (unloaded) and the proximal humerus (normally loaded) in 6-week-old and 6-month-old rats. To confirm the effect of unloading on bone volume and structure, static histomorphometric parameters were measured in the proximal tibial metaphysis. Effects of HU on proliferation of osteoprogenitors were evaluated by measuring the size of CFU-O. HU did not affect the total number of progenitors (CFU-F) in young or adult rats in any of the cell populations. In femoral populations of young rats, HU decreased CFU-O by 71.0% and mean colony size was reduced by 20%. HU decreased CFU-AP by 31.3%. As expected, no changes in CFU-O or CFU-AP were seen in cell populations from the humerus. In femoral cell populations of adult rats, HU decreased CFU-O and CFU-AP by 16.6% and 36.6%, respectively. Again, no effects were seen in cell populations from the humerus. In 6-week-old rats, there was a greater decrease in bone volume, osteoblast number, and osteoblast surface in the proximal tibial metaphysis than that observed in adult rats. Both trabecular thickness and trabecular number were decreased in young rats but remained unaffected in adults. Neither osteoclast number nor surface was affected by unloading. Our results show that the HU-induced decrease in the number of osteoprogenitors observed in vitro parallels the effects of HU on bone volume and osteoblast number in young and old rats in vivo, suggesting that the two may be interdependent. HU also reduced CFU-O colony size in femoral populations indicating a diminished proliferative capacity of osteoblastic colonies.

MOLECULAR THERAPIES FOR DISUSE OSTEOPOROSIS

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Microgravity causes changes in physiological systems that are both detrimental to human health and valuable for biomedical research. Some of the most pronounced and long-term changes occur in skeletal tissue, which experiences a profound and rapid wasting. Finding a countermeasure to the bone atrophy associated with weightlessness is necessary before long-duration human space exploration can be possible. However, these physiological changes can also be exploited as a biomedical model for osteoporosis, offering an extreme environment in which therapeutics can be tested and mechanisms examined. Utilizing space as a biomedical test-bed has been done on several flights: STS-41, 52, 57, 60, 62, 63, 77 and 108, the aims and results of which will be briefly summarized. The rational for spaceflight serving as a biomedical test-bed is that microgravity exposure (and resulting changes in the spacecraft environment) causes an accelerated model for biomedical disorders experienced, often as a result of the normal aging process, here on Earth. The most common target system for these flights was skeletal, with the goal of mimicking osteoporosis, but immune dysfunction, wound healing and muscle atrophy were also studied. Most recently (STS-108, December 2001), the biotechnology company Amgen examined the ability of osteoprotegerin (OPG) to mitigate the osteoporosis caused by microgravity. OPG is a protein that is critical to the differentiation and activation of bone resorbing osteoclasts. Amgen is developing OPG as a treatment for osteoporosis and the bone loss associated with metastatic bone cancer. Over the 12-day flight, the mice experienced a decline in bone strength (15-20% relative to ground controls) that was greater than that of ground-based disuse models. The mechanical testing data was complimented by serum, mRNA and histological analyses that indicated a decline in bone formation and an increase in bone resorption in addition to an inhibition of mineralization. OPG mitigated the decline in mechanical strength by preventing the increase in resorption and maintaining mineralization.

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Spaceflight-induced cardiovascular changes and recovery during NASA's Functional Task Test

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Microgravity-induced physiologic changes could impair a crewmember's performance upon return to a gravity environment. The Functional Task Test aims to correlate these physiologic alterations with changes in performance during mission-critical tasks. In this study, we evaluated spaceflight-induced cardiovascular changes during 11 functional tasks in 7 Shuttle astronauts before spaceflight, on landing day, and 1, 6, and 30 days after landing. Mean heart rate was examined during each task and autonomic activity was approximated by heart rate variability during the Recovery from Fall/Stand Test, a 2-min prone rest followed by a 3-min stand. Heart rate was increased on landing day during all of the tasks, and remained elevated 6 days after landing during 6 of the 11 tasks. Parasympathetic modulation was diminished and sympathovagal balance was increased on landing day. Additionally, during the stand test 6 days after landing, parasympathetic modulation remained suppressed and heart rate remained elevated compared to preflight levels. Heart rate and autonomic activity were not different from preflight levels 30 days after landing. We detected changes in heart rate and autonomic activity during a 3-min stand and a variety of functional tasks, where cardiovascular deconditioning was still evident 6 days after returning from short-duration spaceflight. The delayed recovery times for heart rate and parasympathetic modulation indicate the necessity of assessing functional performance after long-duration spaceflight to ensure crew health and safety.

Effects of mental stress on autonomic cardiac modulation during weightlessness

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Sustained weightlessness affects all body functions, among these also cardiac autonomic control mechanisms. How this may influence neural response to central stimulation by a mental arithmetic task remains an open question. The hypothesis was tested that microgravity alters cardiovascular neural response to standardized cognitive load stimuli. Beat-to-beat heart rate, brachial blood pressure, and respiratory frequency were collected in five astronauts, taking part in three different short-duration (10 to 11 days) space missions to the International Space Station. Data recording was performed in supine position 1 mo before launch; at days 5 or 8 in space; and on days 1, 4, and 25 after landing. Heart rate variability (HRV) parameters were obtained in the frequency domain. Measurements were performed in the control condition for 10 min and during a 5-min mental arithmetic stress task, consisting of deducting 17 from a four-digit number, read by a colleague, and orally announcing the result. Our results show that over all sessions (pre-, in-, and postflight), mental stress induced an average increase in mean heart rate (Δ7 ± 1 beats/min; P = 0.03) and mean arterial pressure (Δ7 ± 1 mmHg; P = 0.006). A sympathetic excitation during mental stress was shown from HRV parameters: increase of low frequency expressed in normalized units (Δ8.3 ± 1.4; P = 0.004) and low frequency/high frequency (Δ1.6 ± 0.3; P = 0.001) and decrease of high frequency expressed in normalized units (Δ8.9 ± 1.4; P = 0.004). The total power was not influenced by mental stress. No effect of spaceflight was found on baseline heart rate, mean arterial pressure, and HRV parameters. No differences in response to mental stress were found between pre-, in-, and postflight. Our findings confirm that a mental arithmetic task in astronauts elicits sympathovagal shifts toward enhanced sympathetic modulation and reduced vagal modulation. However, these responses are not changed in space during microgravity or after spaceflight.

Study of the autonomic regulation of blood circulation during a long-term space flight

by cfynanon 9 June 2015in Biology & Biotechnology No comment

The five-year experience of experimentation in the autonomic regulation of blood circulation on board the International Space Station is presented. The heart rate variability (HRV) analysis was the basic methodical approach in these investigations. The probabilistic approach to the estimation of the risk of pathology under long-term spaceflight conditions based on HRV analysis is described. The individual type of autonomic regulation was taken into account in the analysis of the results of the investigations. The type of regulation inherent in every cosmonaut under the conditions of weightlessness has been shown to be retained during subsequent flights. New scientific data on the relationship between the character of the adaptive response of the body to spaceflight factors and the individual type of autonomic response have been obtained. Staying in weightlessness has been shown to be connected with the readjustment of regulatory systems and with transition to the zone of prenosological states. Adaptation responses in weightlessness are characterized by the increased tension of the regulatory systems and the preservation of sufficient functional reserves. The mobilization of additional resources is required after returning to earth, due to which the functional reserve of the mechanisms of regulation decreases. Cosmonauts with the vagotonic and normosympathotonic types of autonomic regulation appear to be the most resistant. The knowledge of the type of autonomic regulation allows us to judge the potential response of the cosmonaut to spaceflight factors. The likelihood estimates were calculated, and the risk categories were determined by the results of HRV analysis in the last months of the flight. Three pathology risk groups were identified. In conclusion, the theoretical and applied significance of the experiments was considered.

Current problems of space cardiology

by cfynanon 9 June 2015in Biology & Biotechnology No comment

The development of space cardiology is considered, from the first flights of animals and humans to the studies conducted on board International Space Station (ISS). The material is recounted in four sections in accordance with the theoretical statements presented in the book “Space Cardiology” (1967). The first section is analysis of rearrangement of blood circulation under the conditions of microgravity. Long-term microgravity has been demonstrated to require mobilization of additional functional reserves of the body. During the first six months of the flight, the cardiovascular homeostasis is supported by the regulatory mechanisms of the blood circulation system, whereas in the case of a more prolonged impact of microgravity, intersystem control is actively involved (suprasegmental divisions of autonomic regulation). In the second section dealing with the roles of the right and left divisions of the heart in adaptation to microgravity of the cardiovascular system, the important role of the right heart at the initial stage of a space flight (SF) is emphasized. The third section addresses the problem of reducing the orthostatic stability; this study has been initiated as early as the first manned space flights. The results obtained on board ISS testify to the importance of evaluating the functional reserves of the blood circulation system. The fourth section presents data on the new methods of myocardial examination that are to be soon introduced into SF medical provision. In conclusion, some new projects in space cardiology are discussed.

Assessment of individual adaptation to microgravity during long term space flight based on stepwise discriminant analysis of heart rate variability parameters

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Optimization of the cardiovascular system under conditions of long term space flight is provided by individual changes of autonomic cardiovascular control. Heart rate variability (HRV) analysis is an easy to use method under these extreme conditions. We tested the hypothesis that individual HRV analysis provides important information for crew health monitoring. HRV data from 14 Russian cosmonauts measured during long term space flights are presented (two times before and after flight, monthly in flight). HRV characteristics in the time and in the frequency domain were calculated. Predefined discriminant function equations obtained in reference groups (L1=−0.112⁎HR−1.006⁎SI−0.047⁎pNN50−0.086⁎HF; L2=0.140⁎HR−0.165⁎SI−1.293⁎pNN50+0.623⁎HF) were used to define four functional states. (1) Physiological normal, (2) prenosological, (3) premorbid and (4) pathological. Geometric mean values for the ISS cosmonauts based on L1 and L2 remained within normal ranges. A shift from the physiological normal state to the prenosological functional state during space flight was detected. The functional state assessed by HRV improved during space flight if compared to pre-flight and early post-flight functional states. Analysis of individual cosmonauts showed distinct patterns depending on the pre-flight functional state. Using the developed classification a transition process from the state of physiological normal into a prenosological state or premorbid state during different stages of space flight can be detected for individual Russian cosmonauts. Our approach to an estimation of HR regulatory pattern can be useful for prognostic purposes.

Autonomic function testing on board the ISS—update on “Pneumocard”

by cfynanon 9 June 2015in Biology & Biotechnology No comment

The devices “Puls” and “Pneumocard” were developed to further investigate autonomic cardiovascular and respiratory function on board the ISS. Investigations on board the “Mir” station showed transient changes in neurohumoral regulation indicating individual adaptation of regulatory systems. Therefore, an experiment “Pulse” has been performed starting with the fifth expedition on the ISS. The aim of the experiment is to investigate adaptation of the autonomic nervous system by measuring cardiorespiratory parameters during standardized tests at zero-gravity. Our results suggest that the adaptation to zero-gravity in terms of the autonomic cardiorespiratory control was adequate in all cosmonauts ( n = 5 ) . However, the characteristics of the responses during flight depend on the individual regulatory type. The individual evaluation of the regulatory systems especially during the initial stages of flight, during episodes of space sickness and after landing may shed light on critical changes of functional reserves and allow to reduce inflight and postflight disturbances.

Post-Spaceflight Recovery of Biomechanical Properties of Murine Intervertebral Discs

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Prolonged exposure to microgravity during spaceflight is thought to adversely affect the human spine because of reports that disc herniation risk is increased post-spaceflight. The increased herniation risk is highest during the first post-spaceflight year, and gradually subsides thereafter. Consequently, we hypothesized that the biomechanical properties of the intervertebral disc (IVD) deteriorate during spaceflight but then recover after acclimation to normal gravity. To test this hypothesis, we compared the compressive creep properties of caudal IVDs of murine subjects that had returned from a 13-day Shuttle mission (STS-133) to those of ground-based control mice. Spaceflight (n=6) and control (n=10) groups consisted of 13-week-old, BALB/c mice (11 weeks at launch). Mice were sacrificed +1 day, +5 days, or +7 days after the landing of STS-133. Disc height was measured in situ, and compressive creep rate was fit to a fluid transport model to determine disc biomechanical properties. Compared to controls, spaceflight mice had 12.6% lower disc height and 23.1% lower straindependence on swelling pressure. Biomechanical properties did not recover significantly over the 7-day post-flight period. Biomechanical properties of the murine caudal IVD were diminished by spaceflight, consistent with observations that prolonged exposure to microgravity increases disc herniation risk. These properties did not recover after short-term reacclimation to 1g loading.

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Effects of spaceflight on innate immune function and antioxidant gene expression

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Spaceflight conditions have a significant impact on a number of physiological functions due to psychological stress, radiation, and reduced gravity. To explore the effect of the flight environment on immunity, C57BL/6NTac mice were flown on a 13-day space shuttle mission (STS-118). In response to flight, animals had a reduction in liver, spleen, and thymus masses compared with ground (GRD) controls (P < 0.005). Splenic lymphocyte, monocyte/macrophage, and granulocyte counts were significantly reduced in the flight (FLT) mice (P < 0.05). Although spontaneous blastogenesis of splenocytes in FLT mice was increased, response to lipopolysaccharide (LPS), a B-cell mitogen derived from Escherichia coli, was decreased compared with GRD mice (P < 0.05). Secretion of IL-6 and IL-10, but not TNF-α, by LPS-stimulated splenocytes was increased in FLT mice (P < 0.05). Finally, many of the genes responsible for scavenging reactive oxygen species were upregulated after flight. These data indicate that exposure to the spaceflight environment can increase anti-inflammatory mechanisms and change the ex vivo response to LPS, a bacterial product associated with septic shock and a prominent Th1 response.

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Research Containing: Microgravity

Effect of simulated weightlessness on osteoprogenitor cell number and proliferation in young and adult rats

MOLECULAR THERAPIES FOR DISUSE OSTEOPOROSIS

Spaceflight-induced cardiovascular changes and recovery during NASA's Functional Task Test

Effects of mental stress on autonomic cardiac modulation during weightlessness

Study of the autonomic regulation of blood circulation during a long-term space flight

Current problems of space cardiology

Assessment of individual adaptation to microgravity during long term space flight based on stepwise discriminant analysis of heart rate variability parameters

Autonomic function testing on board the ISS—update on “Pneumocard”

Post-Spaceflight Recovery of Biomechanical Properties of Murine Intervertebral Discs

Effects of spaceflight on innate immune function and antioxidant gene expression