Even after transplantation of favourable donor lungs, some recipients require prolonged weaning from mechanical ventilation, indicating a poor prognosis. We investigated the effects of prolonged mechanical ventilation (PMV) for >14 days on the recovery and survival of patients who underwent cadaveric lung transplantation in relation to their physical traits.We retrospectively reviewed patients who underwent cadaveric lung transplantation (age ≥15 years) at a single centre between April 2015 and December 2020 and classified them into PMV and non-PMV groups (>14 and ≤14 days of mechanical ventilation postoperatively, respectively). The factors predicting PMV comprised clinical factors (e.g. marginal donor) and physical features, namely flat chest, narrow fourth intercostal space (length, <5 mm), mediastinal shift, thoracic mediastinal-occupying ratio (TMOR) >40% and sarcopenia, according to the logistic regression analysis. The log-rank test was used to examine the association between TMOR >40% and 3-year prognosis.The PMV group comprised 17 (33%) of 51 recipients. Multivariable logistic analysis showed that the TMOR >40% (odds ratio, 7.3; 95% confidence interval, 1.3-40.1; P = 0.023) was an independent preoperative predictive factor for PMV postoperatively. Stepwise analysis revealed intraoperative extracorporeal membrane oxygenation and reoperation as postoperative predictive factors in addition to TMOR >40%. Recipients with TMOR >40% had significantly worse 3-year survival than other recipients (71.2% vs 100.0%, respectively; P = 0.008).Recipients with a TMOR >40% may be long-term ventilator dependent and have a poor prognosis.
The intestine functions as a barrier preventing the entry of extrinsic factors into the body. This barrier function is disrupted by oxidative damage along with an impaired mucosal layer. Excessive exercise can generate oxidative stress in the intestinal tissue; however, the effect of exercise-induced oxidative stress on intestinal permeability is unclear. In this study, we examined the involvement of oxidative stress in barrier function of the ileum of mice following high-intensity exercise. Male ICR mice (12-week-old) were divided into sedentary and exercise groups. Mice in the exercise group underwent a single bout of treadmill running, and the ileum was collected for histological and biochemical analyses. Plasma fluorescence intensity level after oral administration of fluorescein isothiocyanate-dextran gradually increased until 30 min after exercise in response to intensity of exercise. Relatively high levels of oxidative proteins and low level of claudin-1, a tight-junction protein, were observed in the exercise group. Treatment with a xanthine oxidase inhibitor suppressed exercise-induced increases in intestinal permeability. Moreover, excessive exercise training for two weeks led to relatively high intestinal permeability at rest. These results suggest that high-intensity exercise increases intestinal permeability and tight junction damage, which may be mediated by oxidative stress.
High-intensity exercise training abrogates the aerobic metabolic system in skeletal muscles. Mitochondria play a crucial role in aerobic metabolism and regulate energy supply for muscle contraction. Although the detailed mechanism of mitochondrial dysfunction remains unknown, excessive reactive oxygen species (ROS) generated in response to high-intensity exercise may be involved. Herein, we examined the oxidative modification of mitochondrial proteins in mouse muscle following high-intensity exercise training. Male ICR mice (10-week-old) were divided into sedentary and high-intensity exercise groups. Mice in the exercise group received treadmill training five times per week for two weeks. The levels of oxidative protein modifications and the factors related to mitochondrial biogenesis and dynamics in the gastrocnemius muscle were measured. The levels of hexanoyl lysine adduct (HEL) and 4-hydroxy-2-nonenal (HNE) modified proteins tended to be higher in the muscle mitochondrial fraction, but not whole extractions, of the exercise group than in that of the sedentary group. Specifically, HEL and HNE modifications of malate dehydrogenase 2 (MDH2), a citric acid cycle-related enzyme, were particularly higher in the exercise group mice. Although mitochondrial biogenesis factors were upregulated by exercise, higher phosphorylation of dynamin-related protein 1 (Ser637) was observed in the exercise group. These results suggest that oxidative modification of MDH2 impairs the metabolic system following high-intensity exercise training, which may be associated with attenuated adaptation.
Although supplementation with several antioxidants has been suggested to improve aerobic metabolism during exercise, whether dietary foods containing such antioxidants can exert the metabolic modulation is unclear. This study aimed to investigate the effect of intake of the specific antioxidant-rich foods coupled with exercise training on energy metabolism. Twenty young healthy, untrained men were assigned to antioxidant and control groups: participants in the antioxidant group were encouraged to consume foods containing catechin, astaxanthin, quercetin, glutathione, and anthocyanin. All participants performed cycle training at 60% maximum oxygen consumption for 30 min, 3 days per week for 4 weeks. Maximum work load was significantly increased by training in both groups, while oxygen consumption during exercise was significantly increased in the antioxidant group only. There were positive correlations between maximum work load and fat/carbohydrate oxidations in the antioxidant group. Carbohydrate oxidation during rest was significantly higher in the post-training than that in the pre-training only in the antioxidant group. More decreased levels of serum insulin and HOMA-IR after training were observed in the antioxidant group than in the control group. This study suggests that specific antioxidant-rich foods could modulate training-induced aerobic metabolism of carbohydrate and fat during rest and exercise.
Glutathione is an endogenous redox couple in animal cells and plays important roles in antioxidant defense and detoxification, although it is unknown if oral glutathione supplementation affects exercise-induced physiological changes. The present study investigated the effect of glutathione intake on exercise-induced muscle metabolism and fatigue in mice and humans.ICR mice were divided into 4 groups: sedentary control, sedentary supplemented with glutathione (2.0%, 5 μL/g body weight), exercise control, and exercise supplemented with glutathione. After 2 weeks, the exercise groups ran on a treadmill at 25 m/min for 30 min. Immediately post-exercise, intermuscular pH was measured, and hind limb muscle and blood samples were collected to measure biochemical parameters. In a double-blind, cross-over study, 8 healthy men (35.9 ± 2.0 y) were administered either glutathione (1 g/d) or placebo for 2 weeks. Then, they exercised on a cycle ergometer at 40% maximal heart rate for 60 min. Psychological state and blood biochemical parameters were examined after exercise.In the mouse experiment, post-exercise plasma non-esterified fatty acids were significantly lower in the exercise supplemented with glutathione group (820 ± 44 mEq/L) compared with the exercise control group (1152 ± 61 mEq/L). Intermuscular pH decreased with exercise (7.17 ± 0.01); however, this reduction was prevented by glutathione supplementation (7.23 ± 0.02). The peroxisome proliferator-activated receptor-γ coactivator-1α protein and mitochondrial DNA levels were significantly higher in the sedentary supplemented with glutathione group compared with the sedentary control group (25% and 53% higher, respectively). In the human study, the elevation of blood lactate was suppressed by glutathione intake (placebo, 3.4 ± 1.1 mM; glutathione, 2.9 ± 0.6 mM). Fatigue-related psychological factors were significantly decreased in the glutathione trial compared with the placebo trial.These results suggest that glutathione supplementation improved lipid metabolism and acidification in skeletal muscles during exercise, leading to less muscle fatigue.
Astaxanthin, a xanthophyll carotenoid, accelerates lipid utilization during aerobic exercise, although the underlying mechanism is unclear. The present study investigated the effect of astaxanthin intake on lipid metabolism associated with peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in mice. Mice were divided into 4 groups: sedentary, sedentary and astaxanthin-treated, exercised, and exercised and astaxanthin-treated. After 2 weeks of treatment, the exercise groups performed treadmill running at 25 m/min for 30 min. Immediately after running, intermuscular pH was measured in hind limb muscles, and blood was collected for measurements. Proteins were extracted from the muscle samples and PGC-1α and its downstream proteins were measured by western blotting. Levels of plasma fatty acids were significantly decreased after exercise in the astaxanthin-fed mice compared with those fed a normal diet. Intermuscular pH was significantly decreased by exercise, and this decrease was inhibited by intake of astaxanthin. Levels of PGC-1α and its downstream proteins were significantly elevated in astaxanthin-fed mice compared with mice fed a normal diet. Astaxanthin intake resulted in a PGC-1α elevation in skeletal muscle, which can lead to acceleration of lipid utilization through activation of mitochondrial aerobic metabolism.
This study aimed to investigate the effect of downhill walking on muscle damage and glucose metabolism in healthy subjects. All ten healthy young men and women (age, 24.0 ± 1.4 years) performed rest, uphill walking, and downhill walking trials. In the exercise trials, uphill (+ 5%) or downhill (− 5%) treadmill walking was performed at 6 km/h for 30 min. On the next day, muscle soreness was significantly higher in the downhill trial than in the uphill trial (P < 0.01). Respiratory metabolic performance did not differ between trials. However, carbohydrate oxidation was negatively correlated with plasma creatine kinase (r = − 0.41) and muscle soreness (r = − 0.47). Fasting blood glucose was significantly lower in the uphill trial than in the rest trial (P < 0.01) but not in the downhill trial. These observations suggest that downhill but not uphill walking causes mild delayed-onset muscle damage, which did not cause marked impairment in glucose metabolism. However, higher muscle damage responders might exhibit lower glucose metabolism.
