MOLECULAR THERAPIES FOR DISUSE OSTEOPOROSIS

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

by on 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.

Related URLs:
http://dx.doi.org/10.1134/S0362119713050046

The Effects of Long-term Microgravity on Autonomic Regulation of Blood Circulation in Crewmembers of the International Space Station

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The article presents the results of space experiment “Pneumocard”. The investigation involved all 25 Russian members of the ISS crew. The total of 226 sessions were made including 130 aboard the ISS, 50 prior to launch and 46 on return from mission. The objective was to study effects of the spaceflight factors on autonomic regulation of blood circulation, respiration and cardiac contractility during long-duration mission. The purpose was to secure new research data that would clarify our present view of adaptation mechanisms. Registered were the following signals: electrocardiogram, impedance cardiogram, seismic cardiogram, pneumotachogram, finger photoplethysmogram. A set of hardand software was used. Autonomic regulation of blood circulation by HRV analysis was investigated. It was shown that at the onset of a space mission parasympathetic involvement in regulation increases typically with subsequent mobilization of additional functional reserve. It guided the development of a functional states mathematical model incorporating the established types of autonomic regulation. Our data evidence that the combination of HRV analysis, pre-nosology diagnosis and probabilistic estimate of the pathology risk can reinforce the medical care program in space missions.

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Current problems of space cardiology

by on 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.

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http://dx.doi.org/10.1134/S0362119710070042

Autonomic cardiovascular and respiratory control during prolonged spaceflights aboard the International Space Station

by on 9 June 2015in Biology & Biotechnology No comment

Impaired autonomic control represents a cardiovascular risk factor during long-term spaceflight. Little has been reported on blood pressure (BP), heart rate (HR), and heart rate variability (HRV) during and after prolonged spaceflight. We tested the hypothesis that cardiovascular control remains stable during prolonged spaceflight. Electrocardiography, photoplethysmography, and respiratory frequency (RF) were assessed in eight male cosmonauts (age 41–50 yr, body-mass index of 22–28 kg/m2) during long-term missions (flight lengths of 162–196 days). Recordings were made 60 and 30 days before the flight, every 4 wk during flight, and on days 3 and 6 postflight during spontaneous and controlled respiration. Orthostatic testing was performed pre- and postflight. RF and BP decreased during spaceflight (P < 0.05). Mean HR and HRV in the low- and high-frequency bands did not change during spaceflight. However, the individual responses were different and correlated with preflight values. Pulse-wave transit time decreased during spaceflight (P < 0.05). HRV reached during controlled respiration (6 breaths/min) decreased in six and increased in one cosmonaut during flight. The most pronounced changes in HR, BP, and HRV occurred after landing. The decreases in BP and RF combined with stable HR and HRV during flight suggest functional adaptation rather than pathological changes. Pulse-wave transit time shortening in our study is surprising and may reflect cardiac output redistribution in space. The decrease in HRV during controlled respiration (6 breaths/min) indicates reduced parasympathetic reserve, which may contribute to postflight disturbances.

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http://jap.physiology.org/jap/103/1/156.full.pdf

Prospects of medical monitoring of long-duration space flights by means of non-contact recording of physiological functions during sleep time

by on 9 June 2015in Biology & Biotechnology No comment

The methods used to investigate the body functional state in sleep under the conditions of a long-duration space flight are of great scientific and practical interest. The Sonocard experiment is based on the method of seismocardiography. The goal of this experiment is to validate and improve the procedure of non-contact recording the in-sleep physiological data for monitoring the crew state. The very first results have demonstrated that, as on Earth, sleep is crucial for recovery of the functional reserves expended during the daytime under the conditions of microgravity. Using the new technology, the recovery processes, as well as individual adaptation to a long-term space flight, can be studied. This method makes it possible to evaluate the sleep quality, mechanisms of recreation, and body functionality. These data may enrich substantially the information used by medical operators of space missions in the control centers.

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http://dx.doi.org/10.1134/S036211971107005X

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

by on 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.

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http://www.sciencedirect.com/science/article/pii/S0094576511002189

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

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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.

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http://www.sciencedirect.com/science/article/pii/S0094576506004164

Post-Spaceflight Recovery of Biomechanical Properties of Murine Intervertebral Discs

by on 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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Effect of microgravity on the biomechanical properties of lumbar and caudal intervertebral discs in mice

by on 9 June 2015in Biology & Biotechnology No comment

Prolonged exposure to microgravity has shown to have deleterious effects on the human spine, indicated by low back pain during spaceflight and increased incidence of post-spaceflight herniated nucleus pulposus. We examined the effect of microgravity on biomechanical properties of lumbar and caudal discs from mice having been on 15-day shuttle mission STS-131. Sixteen C57BL/C mice (spaceflight group, n=8; ground-based control group, n=8) were sacrificed immediately after spaceflight. Physiological disc height (PDH) was measured in situ, and compressive creep tests were performed to parameterize biomechanical properties into endplate permeability (k), nuclear swelling pressure strain dependence (D), and annular viscoelasticity (G). For caudal discs, the spaceflight group exhibited 32% lower PDH, 70% lower D and crept more compared to the control mice (p=0.03). For lumbar discs, neither PDH nor D was significantly different between murine groups. Initial modulus, osmotic pressure, k and G for lumbar and caudal discs did not appear influenced by microgravity (p>0.05). Decreases in both PDH and D suggest prolonged microgravity effectively diminished biomechanical properties of caudal discs. By contrast, differences were not noted for lumbar discs. This potentially deleterious interaction between prolonged weightlessness and differential ranges of motion along the spine may underlie the increased cervical versus lumbar disc herniation rates observed among astronauts.

Related URLs:
http://www.ncbi.nlm.nih.gov/pubmed/25085756
http://www.jbiomech.com/article/S0021-9290(14)00386-8/abstract