Effects of Microgravity on Human Physiology

The effects of microgravity conditions on neurovestibular, cardiovascular, musculoskeletal, bone metabolic, and hemato-immunological systems are described. We discuss “space motion sickness,” sensorimotor coordination disorders, cardiovascular deconditioning, muscular atrophy, bone loss, and anemia/immunodeficiency, including their causes and mechanisms. In addition to the previously described deconditioning, new problems related to microgravity, spaceflight-associated neuro-ocular syndrome (SANS), and structural changes of the brain by magnetic resonance imaging (MRI) are also explained. Our proposed countermeasure, artificial gravity produced by a short-arm centrifuge with ergometric exercise, is also described in detail, and we confirmed this system to be effective in preventing the abovementioned deconditioning caused by microgravity exposure

Intracellular oxygen tension limits muscle contraction-induced change in muscle oxygen consumption under hypoxic conditions during Hb-free perfusion.

Under acute hypoxic conditions, the muscle oxygen uptake (mV˙O2) during exercise is reduced by the restriction in oxygen-supplied volume to the mitochondria within the peripheral tissue. This suggests the existence of a factor restricting the mV˙O2 under hypoxic conditions at the peripheral tissue level. Therefore, this study set out to test the hypothesis that the restriction in mV˙O2 is regulated by the net decrease in intracellular oxygen tension equilibrated with myoglobin oxygen saturation (∆PmbO2) during muscle contraction under hypoxic conditions. The hindlimb of male Wistar rats (8 weeks old, n = 5) was perfused with hemoglobin-free Krebs-Henseleit buffer equilibrated with three different fractions of O2 gas: 95.0%O2, 71.3%O2, and 47.5%O2 The deoxygenated myoglobin (Mb) kinetics during muscle contraction were measured under each oxygen condition with a near-infrared spectroscopy. The ∆[deoxy-Mb] kinetics were converted to oxygen saturation of myoglobin (SmbO2), and the PmbO2 was then calculated based on the SmbO2 and the O2 dissociation curve of the Mb. The SmbO2 and PmbO2 at rest decreased with the decrease in O2 supply, and the muscle contraction caused a further decrease in SmbO2 and PmbO2 under all O2 conditions. The net increase in mV˙O2 from the muscle contraction (∆mV˙O2) gradually decreased as the ∆PmbO2 decreased during muscle contraction. The results of this study suggest that ΔPmbO2 is a key determinant of the ΔmV˙O2

Endurance training facilitates myoglobin desaturation during muscle contraction in rat skeletal muscle.

At onset of muscle contraction, myoglobin (Mb) immediately releases its bound O2 to the mitochondria. Accordingly, intracellular O2 tension (PmbO2) markedly declines in order to increase muscle O2 uptake (mVO2). However, whether the change in PmbO2 during muscle contraction modulates mVO2 and whether the O2 release rate from Mb increases in endurance-trained muscles remain unclear. The purpose of this study was, therefore, to determine the effect of endurance training on O2 saturation of Mb (SmbO2) and PmbO2 kinetics during muscle contraction. Male Wistar rats were subjected to a 4-week swimming training (Tr group; 6 days per week, 30 min × 4 sets per day) with a weight load of 2% body mass. After the training period, deoxygenated Mb kinetics during muscle contraction were measured using near-infrared spectroscopy under hemoglobin-free medium perfusion. In the Tr group, the VmO2peak significantly increased by 32%. Although the PmbO2 during muscle contraction did not affect the increased mVO2 in endurance-trained muscle, the O2 release rate from Mb increased because of the increased Mb concentration and faster decremental rate in SmbO2 at the maximal twitch tension. These results suggest that the Mb dynamics during muscle contraction are contributing factors to faster VO2 kinetics in endurance-trained muscle

NIRS measurement of O(2) dynamics in contracting blood and buffer perfused hindlimb muscle.

金沢大学人間社会研究域人間科学系In order to obtain evidence that Mb releases O(2) during muscle contraction, we have set up a buffer-perfused hindlimb rat model and applied NIRS to detect the dynamics of tissue deoxygenation during contraction. The NIRS signal was monitored on hindlimb muscle during twitch contractions at 1 Hz, evoked via electrostimulator at different submaximal levels. The hindlimb perfusion was carried out by perfusion of Krebs Bicarbonate buffer. The NIRS still detected a strong signal even under Hb-free contractions. The deoxygenation signal (Delta[deoxy]) was progressively increased at onset of the contraction and reached the plateau under both blood- and buffer-perfused conditions. However, the amplitude of Delta[deoxy] during steady state continued to significantly increase as tension increased. The tension-matched comparison of the Delta[deoxy] level under buffer-perfused and blood perfused conditions indicate that Mb can contribute approximately 50% to the NIRS signal. These results clarify the Mb contribution to the NIRS signal and show a falling intracellular PO(2) as workload increases

Quantification of myoglobin deoxygenation and intracellular partial pressure of O2 during muscle contraction during haemoglobin-free medium perfusion

金沢大学人間社会研究域人間科学系Although the O2 gradient regulates O2 flux from the capillary into the myocyte to meet the energy demands of contracting muscle, intracellular O2 dynamics during muscle contraction remain unclear. Our hindlimb perfusion model allows the determination of intracellular myoglobin (Mb) saturation () and intracellular oxygen tension of myoglobin () in contracting muscle using near infrared spectroscopy (NIRS). The hindlimb of male Wistar rats was perfused from the abdominal aorta with a well-oxygenated haemoglobin-free Krebs-Henseleit buffer. The deoxygenated Mb (Δ[deoxy-Mb]) signal was monitored by NIRS. Based on the value of Δ[deoxy-Mb], and were calculated, and the time course was evaluated by an exponential function model. Both and started to decrease immediately after the onset of contraction. The steady-state values of and progressively decreased with relative work intensity or muscle oxygen consumption. At the maximal twitch rate, and were 49% and 2.4 mmHg, respectively. Moreover, the rate of release of O2 from Mb at the onset of contraction increased with muscle oxygen consumption. These results suggest that at the onset of muscle contraction, Mb supplies O2 during the steep decline in, which expands the O2 gradient to increase the O2 flux to meet the increased energy demands. © 2010 The Physiological Society

Baroreflex control of muscle sympathetic nerve activity after 120 days of 6°head-down bed rest

of muscle sympathetic nerve activity after 120 days of 6°head-down bed rest. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 278: R445-R452, 2000.-To examine how long-lasting microgravity simulated by 6°head-down bed rest (HDBR) induces changes in the baroreflex control of muscle sympathetic nerve activity (MSNA) at rest and changes in responses of MSNA to orthostasis, six healthy male volunteers (range 26-42 yr) participated in Valsalva maneuver and head-up tilt (HUT) tests before and after 120 days of HDBR. MSNA was measured directly using a microneurographic technique. After long-term HDBR, resting supine MSNA and heart rate were augmented. The baroreflex slopes for MSNA during Valsalva maneuver (in supine position) and during 60°HUT test, determined by least-squares linear regression analysis, were significantly steeper after than before HDBR, whereas the baroreflex slopes for R-R interval were significantly flatter after HDBR. The increase in MSNA from supine to 60°HUT was not different between before and after HDBR, but mean blood pressure decreased in 60°HUT after HDBR. In conclusion, the baroreflex control of MSNA was augmented, whereas the same reflex control of R-R interval was attenuated after 120 days of HDBR. microneurography; orthostatic hypotensio

Common Peak Approach Using Mass Spectrometry Data Sets for Predicting the Effects of Anticancer Drugs on Breast Cancer

We propose a method for biomarker discovery from mass spectrometry data, improving the common peak approach developed by Fushiki et al. (BMC Bioinformatics, 7:358, 2006). The common peak method is a simple way to select the sensible peaks that are shared with many subjects among all detected peaks by combining a standard spectrum alignment and kernel density estimates. The key idea of our proposed method is to apply the common peak approach to each class label separately. Hence, the proposed method gains more informative peaks for predicting class labels, while minor peaks associated with specific subjects are deleted correctly. We used a SELDI-TOF MS data set from laser microdissected cancer tissues for predicting the treatment effects of neoadjuvant therapy using an anticancer drug on breast cancer patients. The AdaBoost algorithm is adopted for pattern recognition, based on the set of candidate peaks selected by the proposed method. The analysis gives good performance in the sense of test errors for classifying the class labels for a given feature vector of selected peak values

Dynamic Rupture Simulations Based on the Characterized Source Model of the 2011 Tohoku Earthquake

The 2011 Off the Pacific Coast of Tohoku earthquake (Tohoku earthquake, M_w 9.0) occurred on the Japan Trench and caused a devastating tsunami. Studies of this earthquake have revealed complex features of its rupture process. In particular, the shallow parts of the fault (near the trench) hosted large slip and long period seismic wave radiation, whereas the deep parts of the rupture (near the coast) hosted smaller slip and strong radiation of short period seismic waves. Understanding such depth-dependent feature of the rupture process of the Tohoku earthquake is necessary as it may occur during future mega-thrust earthquakes in this and other regions. In this study, we investigate the “characterized source model” of the Tohoku earthquake through dynamic rupture simulations. This source model divides the fault plane into several parts characterized by different size and frictional strength (main asperity, background area, etc.) and is widely used in Japan for the prediction of strong ground motion and tsunami through kinematic rupture simulations. Our characterized source model of the Tohoku earthquake comprises a large shallow asperity with moderate frictional strength, small deep asperities with high frictional strength, a background area with low frictional strength, and an area with dynamic weakening close to the trench (low dynamic friction coefficient as arising from, e.g., thermal pressurization). The results of our dynamic rupture simulation reproduce the main depth-dependent feature of the rupture process of the Tohoku earthquake. We also find that the width of the area close to the trench (equal to the distance from the trench to the shallow asperity, interpreted as the size of the accretionary prism) and the presence of dynamic weakening in this area have a significant influence on the final slip distribution. These results are useful to construct characterized source models for other subduction zones with different scale of the accretionary prism, such as the Chile subduction zone and the Nankai Trough. Dynamic rupture simulations based on the characterized source model might provide useful insights for hazard assessment associated with future mega-thrust earthquakes