Long-time Exercise Research Articles

Exercise induces tissue hypoxia and HIF-1α redistribution in the small intestine

BackgroundExercise induces blood flow redistribution among tissues, leading to splanchnic hypoperfusion. Intestinal epithelial cells are positioned between the anaerobic lumen and the highly metabolic lamina propria with an oxygen gradient. Hypoxia-inducible factor (HIF)-1α is pivotal in the transcriptional response to the oxygen flux. MethodsIn this study, the pimonidazole hydrochloride staining was applied to observe the tissue hypoxia in different organs, which might be affected by the blood flow redistribution. The HIF-1α luciferase reporter ROSA26 oxygen-dependent degradation domain (ODD)-Luc/+ mouse model (ODD domain-Luc; female, n = 3–6/group) was used to detect the HIF-1α expression in the intestine. We used 3 swimming models: moderate exercise for 30 min, heavy-intensity exercise bearing 5% bodyweight for 1.5 h, and long-time exercise for 3 h. ResultsWe found that 1 session of swimming at different intensities could induce tissue hypoxia redistribution in the small intestine, colon, liver and kidney, but not in the spleen, heart, and skeletal muscle. Our data showed that exercise exacerbated the extent of physiological hypoxia in the small intestine. Next, using ODD-Luc mice, we found that moderate exercise increased the in vivo HIF-1α level in the small intestine. The post-exercise HIF-1α level was gradually decreased in a time-dependent manner. Interestingly, the redistribution of tissue hypoxia and the increase of HIF-1α expression were not related to the exercise intensity and duration. ConclusionThis study provided evidence that the small intestine is the primary target organ for exercise-induced tissue hypoxia and HIF-1α redistribution, suggesting that HIF-1α may be a potential target for the regulation of gastrointestinal functions after exercise.

Overlap of periodic paralysis and paramyotonia congenita caused by SCN4A gene mutations two family reports and literature review

ABSTRACTObjective: To verify the diagnosis of channelopathies in two families and explore the mechanism of the overlap between periodic paralysis (PP) and paramyotonia congenita (PMC). Methods: We have studied two cases with overlapping symptoms of episodic weakness and stiffness in our clinical center using a series of assessment including detailed medical history, careful physical examination, laboratory analyses, muscle biopsy, electrophysiological evaluation, and genetic analysis. Results: The first proband and part of his family with the overlap of PMC and hyperkalemic periodic paralysis (HyperPP) has been identified as c.2111C > T (T704M) substitution of the gene SCN4A. The second proband and part of his family with the overlap of PMC and hypokalemic periodic paralysis type 2 (HypoPP2) has been identified as c.4343G > A (R1448H) substitution of the gene SCN4A. In addition, one member of the second family with overlapping symptoms has been identified as a novel mutation c.2111C > T without the mutation c.4343G > A. Conclusions: SCN4A gene mutations can cause the overlap of PMC and PP (especially the HypoPP2). The clinical symptoms of episodic weakness and stiffness could happen at a different time or temperature. Based on diagnosis assessments such as medical history and muscle biopsy, further evaluations on long-time exercise test, genetic analysis, and patch clamp electrophysiology test need to be done in order to verify the specific subtype of channelopathies. Furthermore, the improvement of one member in the pregnancy period can be used as a reference for the other female in the child-bearing period with T704M.

OR-026 Exercise induces HIF-1α redistribution in the small intestine

Objective Intestinal epithelial cells are positioned between an anaerobic lumen and a highly metabolic lamina propria, affected by reduced blood flow and tissue hypoxia. Exercise induces blood flow redistribution, leading to hypoperfusion and gastrointestinal (GI) compromise. The hypoxia-inducible factor (HIF) 1α is pivotal in the transcriptional response to oxygen flux. In this study, we hypothesized that exercise induces GI system hypoxia and accumulates HIF-1α.
 Methods (1) ROSA26 ODD-Luc/+ mouse model (ODD-Luc) was used to detect HIF-1α expression in the intestine (female, 8-week, n=6/group). ODD-Luc mice were randomized into 4 groups: stayed in 21% O2 as the normoxic control (C), exercise (E), injected HIF-1α inhibitor PX-478 before swimming (PS), placed in the chamber containing 9% O2 for 4 hours as the positive control (PC). (2) Exercise models were conducted by volume: Moderate Exercise (ME): mice voluntarily swam for 30 min; Heavy-intensity Exercise (HE): mice swam for 1.5 hours with 5% body weight loads attached to their tails; Long-time Exercise (LE): mice voluntarily swam for 3 hours or till fatigue.
 Results (1) Exercise increased HIF-1α in the abdominal area. The luciferase activities boosted after exercise, compared to the controls (ME v.s. C, P<0.05; HE v.s. C, P<0.05; LE v.s. C, P<0.05) but no differences among three exercise groups (ME v.s. HE, P>0.99; ME v.s. LE, P>0.99; HE v.s. LE, P>0.99); (2) Exercise altered HIF-1α distribution in the small intestine in a time-dependent manner. The expression of HIF-1α was significantly increased after exercise and gradually reduced to the rest level. The photons increased at the 0th hour after exercise compared to that of the normoxic control (P<0.01). The level of photons then reduced over time, while the 2nd, 4th and 6th hour post-exercise were still greater than that of the normoxic control (2nd hour v.s. C, P<0.01; 4th hour v.s. C, P<0.01; 6th hour v.s. C, P<0.05), and returned to normal after 24 hours (24th hour v.s. C, P>0.99).
 Conclusions Exercise induced the distribution of HIF-1α in the small intestine. The expression of HIF-1α is shown in a time-dependent manner after exercise.

PO-154 Exercise induced redistribution of oxygen in internal organs

Objective Exercise induces tissue blood flow redistribution, which decreases splanchnic circulation and leads to physiologic hypoxia in the gastrointestinal (GI) system and liver. We hypothesized that the oxygen redistribution in the internal organs is affected by exercise.
 Methods Twenty–four female 8-10wk ROSA26 ODD-Luc/+ mice (n= 6 per group) were used in this study. Three exercise models were conducted: (1) Moderate Exercise (ME): mice voluntarily swam for 30 min. (2) Heavy-intensity Exercise (HE): mice swam for 1.5 hours with 5% body weight loads attached to their tails. (3) Long-time Exercise (LE): mice voluntarily swam for 3 hours or till fatigue. Sedentary mice (SED) were used as controls. A hypoxic marker pimonidazole HCl was applied to detect tissue hypoxia. Pimonidazole HCl forms protein adducts when PO2 is under 10 mmHg. An hour after intraperitoneal injection of pimonidazole HCl (60 mg/kg body weight), the mice were anesthetized with isoflurane then sacrificed. The small intestine, colon, skeletal muscle, heart, liver, spleen and kidney specimens were fixed in 4% paraformaldehyde and stained with a specific monoclonal antibody against the pimonidazole HCl protein adducts to observe the hypoxic level of internal organs.
 Results (1) The distributions of immunostaining intensity of pimonidazole HCl were different among the internal organs. In the kidney, the renal tubules demonstrated staining for hypoxia. In the liver, the positive staining was radiating outwards from central veins. In the small intestine and colon, there was the retention of pimonidazole HCl from the crypt to villus. (2) In the ME group, the extent of hypoxia in the kidney, liver and colon was increased compared with the SED. We found the small intestine is susceptible to exercise-induced tissue hypoxia distribution. Exercise resulted in a markedly increased staining in the crypts, whereas decreased staining in the villus. Intensified positive stains were observed in the nuclei of hypoxic cells, mostly in ME and HE groups. (3) The heart, skeletal muscle and spleen were not shown positive staining pre- and post-exercise.
 Conclusions This study presented evidences that exercise induces the oxygen redistribution in the small intestine, colon, liver and kidney. The small intestine is susceptible to exercise induced physiological hypoxia.

Comparison of Tibial Torsion Angles Between Elite Athletes and Sedentary People

Torsion is described as a rotational deformation where a long bone turns longitudinally around its own axe. Torsion in tibia is the main reason of children’s stepping in-toe and out-toe. It not only creates orthopedic problems in the future, but also is a risk factor for lower extremity injuries. This study intends to compare Tibial Torsion Angle (TTA) of sedentary people to the soccer players of a Turkish Super Leage team. By comparing TTA angles of elite soccer players who train and compete regularly and have high level of muscle power and endurance to the sedentary control group, it is aimed to determine whether high level soccer training effect TTA. The research was conducted between June-October 2015 on 25 elite soccer players and 25 sedantary people by measuring their right and left tibial torsion angles via transmalleolar measurement with a goniometer. Non-parametric tests were used in statistical analysis, Mann-Whitney U test was used for comparisons. There was not a significant difference in right-left measurements within groups. Between groups right TTA showed no significant difference but left TTA measurements varied significantly (p ˂ 0.05). These findings suggest that tibial torsion angle differs according to physical activity level. It is understood that regular and long-time exercise programmes can change TTA.

Reference value of long-time exercise test in the diagnosis of primary periodic paralysis

The long-time exercise test (ET) is used to diagnose the primary periodic paralyses (PPs). However the reference values of ET are many and various. This study aimed to investigate the reference value of long-time ET in the diagnosis of PPs. We recruited 108 healthy subjects, 68 patients with PPs, and 72 patients with other diseases for the study. The procedure of ET was made on the basis of the McManis' method. Electrical responses were recorded from right abductor digiti minimi (ADM) muscle when stimulation of the ulnar nerve at the wrist. After the compound muscle action potential (CMAP) was monitored, subjects were then asked to contract the muscle as strongly as possible for 5 minutes. CMAPs were recorded for 2 seconds immediately after cessation of exercise, then every 5 minutes for 10 minutes, and finally every 10 minutes for 50 minutes. In general, the CMAP amplitudes will fall below the pre-exercise levels in an hour. The largest decrease was calculated and used as results of ET. The CMAP amplitude decreases had no significant differences between groups when the healthy adults were grouped according to age, gender, height, weight and test time. Decreases in PPs patients (57.76%) were significantly more than in healthy subjects (15.21%) and other disease patients (18.10%, P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that the best threshold is 35.50%. In the long-time exercise test, threshold of 35.50% for the CMAP amplitude decrease was identified for abnormal. The result is not influenced by age, gender, height, weight, and test time. About 7.4% of healthy subjects were abnormal in ET.