Norio Hotta

The adaptive responses in several mediators linked with hypertrophy and atrophy of skeletal muscle after lower limb unloading in humans

Aim:  To determine the adaptive changes in several molecules regulating muscle hypertrophy and atrophy after unloading, we examined whether unilateral lower limb suspension changes the mRNA and protein levels of SRF‐linked (RhoA, RhoGDI, STARS and SRF), myostatin‐linked (myostatin, Smad2, Smad3 and FLRG) and Foxo‐linked (P‐Akt, Foxo1, Foxo3a and Atrogin‐1) mediators.

Changes in ventilatory responses to hypercapnia and hypoxia after intermittent hypoxia in humans

The purpose of this study was to clarify the changes in hypercapnic and hypoxic ventilatory responses (HCVR and HVR) after intermittent hypoxia and following the cessation of hypoxic exposure. Twenty-nine males were assigned to one of four groups, i.e., a hypoxic (EX1-H, n=7) or a control (EX1-C, n=7) group in Experiment 1, and a hypoxic (EX2-H, n=8) or a control (EX2-C, n=7) group in Experiment 2. In each experiment, the hypoxic tent system was utilized for intermittent hypoxia, and the oxygen levels in the tent were maintained at 12.3+/-0.2%. In Experiment 1, the EX1-H group spent 3 h/day in the hypoxic tent for 1 week. HCVR and HVR were determined before and after 1 week of intermittent hypoxia, and again 1 and 2 week after the cessation of hypoxic exposure. In Experiment 2, the subjects in the EX2-H group performed 3 h/day for 2 weeks in intermittent hypoxia. HCVR and HVR tests were carried out before and after intermittent hypoxia, and were repeated again after 2 weeks of the cessation of hypoxic exposure. The slope of the HCVR in the EX1-H group did not show a significant increase after 1 week of intermittent hypoxia, while HCVR in the EX2-H group increased significantly after 2 weeks of intermittent hypoxia. The HCVR intercept was unchanged following 1 or 2 weeks of intermittent hypoxia. There was a significant increase in the slope of the HVR after 1 and 2 weeks of intermittent hypoxia. The increased HCVR and HVR returned to pre-hypoxic levels after 2 weeks of the cessation of hypoxia. These results suggest that 3 h/day for 2 weeks of intermittent hypoxia leads to an increase in central hypercapnic ventilatory chemosensitivity, which is not accompanied by a re-setting of the central chemoreceptors, and that the increased hypercapnic and hypoxic chemosensitivities are restored within 2 weeks after the cessation of hypoxia.

Cycle Ergometer Exercise to Counteract Muscle Atrophy During Unilateral Lower Limb Suspension

INTRODUCTION Atrophy of the leg muscles is a serious consequence of disuse and occurs with prolonged exposure to microgravity. We investigated whether intense interval training on a cycle ergometer would prevent muscle changes during unilateral lower limb suspension (ULLS). METHODS This study involved 11 healthy men who were divided into 2 groups, one with training on a cycle ergometer (TRN, N=6) and the other a control group (CON, N=5). TRN performed intense interval training (up to 90% of maximum heart rate) on alternate days during 20 d of unloading. Maximum voluntary contraction (MVC) of the quadriceps femoris and volume of the thigh muscle were measured before and after unloading. Muscle functional magnetic resonance imaging (mfMRI), which reflects the contractile activity of the activating muscle, were acquired during submaximal dynamic knee extension exercises. RESULTS The MVC was significantly decreased in TRN (-11.1%) and CON (-18.7%). The total volume of the thigh muscles was maintained in TRN (-0.2%); however, a significant decrease was found in CON (-6.9%). The mfMRI signal increase for submaximal exercise did not change for TRN; however, it significantly increased for CON. CONCLUSIONS Although the power of this study was limited, these results suggest that training on a cycle ergometer counteracts some of the effects of unloading and merits further study as a potential countermeasure for muscle changes in microgravity.

Aerobic exercise capacity and muscle volume after lower limb suspension with exercise countermeasure.

INTRODUCTION The purpose of the present study was to elucidate the effect of unilateral lower limb suspension (ULLS) on aerobic capacity during one-legged cycle exercise and whether the change in aerobic exercise capacity after ULLS with or without intensive interval training is related to the change in skeletal muscle volume. METHODS There were 13 young men who underwent 20 d of ULLS and were divided into 2 groups based on some physical characteristics: the control group (CON; N=7) and the trained group (TRN; N=6). Subjects in TRN underwent interval cycle training on alternate days during ULLS. The respiratory and circulatory responses to one-legged incremental cycling and muscle volume of the thigh were measured before and after 20 d of ULLS. RESULTS : One-legged peak oxygen uptake (VO2peak) and total muscle volume of the thigh in CON decreased significantly after 20 d of ULLS (-11.0 +/- 3.5% in VO2peak, -6.1 +/- 1.8% in total muscle volume). However, these parameters were maintained in TRN (+0.2 +/- 5.2% in VO2peaka, -1.0 +/- 1.8% in total muscle volume). Circulatory variables at rest and during submaximal exercise were unchanged in both groups after ULLS. Changes in one-legged VO2peak were significantly correlated with change in total muscle volume of the thigh in CON. CONCLUSION Our findings indicated that peripheral adaptations after ULLS could relate to the change in aerobic exercise capacity during one-legged exercise. Our results also suggest that intensive interval training prevents ULLS-induced deconditioning of both aerobic exercise capacity and skeletal muscle volume.

Low pH Enhances Response of Thin Muscle Afferents to Mechanical Stimuli

We examined whether acidic buffer sensitizes thin muscular afferents to mechanical stimulus using single-fiber recording. The EDL muscle with the common peroneal nerve attached was excised from 17-male SD rats under pentobarbital anesthesia. After identifying single thin afferent fibers, mechanical stimulus was applied to their receptive fields using a servo-controlled mechanical stimulator before and after pH 6.2-solution was applied to the receptive field. The effect of pH 7.4-solution was similarly examined as a control. Application of pH 7.4-solution did not induce any change in the mechanical threshold or increase in the number of discharges evoked during stimulation over the number of spontaneous discharges (response magnitude). However, pH 6.2-solution significantly lowered the mechanical threshold and increased the response magnitude, suggesting that the mechanical sensitivity of thin muscle afferents was augmented by exposure to acidic pH, which is seen during exercise. This change could be involved in respiratory control during exercise.

Effect of intensive interval training during unloading on muscle deoxygenation kinetics.

The present study investigated the effects of intensive interval training during 20-day of unloading on local muscle oxygenation kinetics evaluated by near infrared spectroscopy technique (NIRS). Eleven adult men completed 20-day unloading and were divided into two groups; the control (CON) group and training (TR) group. The TR group engaged in exercise training sessions that consisted of one-legged submaximal cycle exercise using the unloaded leg at 60 approximately 80% of VO(2peak) with intermittent rest periods, 25 min/day every other day. All subjects performed isometric knee extension exercise at 50% of their maximum voluntary contraction force before and after unloading. NIRS Delta[deoxy-Hb/Mb] signal was recorded from m. vastus lateralis and was fitted to an exponential equation in order to determine the kinetics parameters. The time constant (tau) of the % Delta[deoxy-Hb/Mb] was unchanged in the TR group, while it significantly increased in the CON group after unloading (pre, 5.0+/-1.0; post, 7.4+/-1.0 s). It is concluded that 20-day unloading increased the tau, suggesting deterioration of capacity for oxidative phosphorylation and oxygen utilization in a skeletal muscle. Additionally, the preservation of tau in the TR group suggested that intensive interval training could have an impact on the maintenance of muscle oxidative metabolism during unloading.

Effect of protons on the mechanical response of rat muscle nociceptive fibers and neurons in vitro.

Strong exercise makes muscle acidic, and painful. The stimulus that activates muscle nociceptors in such instance may be protons. Reportedly, however, not many afferents are excited by protons alone. We, therefore, posited that protons sensitize muscular nociceptors to mechanical stimuli. We examined effects of protons on mechanical sensitivity of muscle nociceptors by single-fiber recording from rat muscle-nerve preparations in vitro and by whole cell patch-clamp recording of mechanically activated (MA) currents from cultured rat dorsal root ganglion neurons. We recorded 38 Aδ- and C-fibers. Their response magnitude was increased by both pH 6.2 and pH 6.8; in addition the mechanical threshold was lowered by pH 6.2. Decrease in the threshold by pH6.2 was also observed in MA currents. Presently observed sensitization by protons could be involved in several types of ischemic muscle pain, and may also be involved in cardiovascular and respiratory controls during exercise.

Effects of Deconditioning on the Initial Ventilatory and Circulatory Responses at the Onset of Exercise in Man

In order to elucidate the effects of deconditioning (inactivity) on the ventilatory and circulatory responses at the onset of exercise within 20 s, we initiated head-down bed rest and unilateral lower limb suspension experiments, and measured these responses to dynamic voluntary leg exercise and passive movements. Initial ventilatory and heart rate responses to voluntary exercise were attenuated after bed rest but showed no change after suspension or during passive movements, suggesting the minimal role of peripheral neural reflex.