| BACKGROUND: The damage of plateau hypoxia environment to the human body has been widely recognized,and there are a lot of researches on the injury caused by exercise stress. But the effect of exercise stress under radical hypoxia on human especially the impact and mechanism on cardiac structure and function are still unclear at present for lack of study. Undertaking a gradual ascent to plateau or using oxygen remains the best method currently for the prevention and treatment of acute altitude illness,but not convenient for a large number of people in the rapid ascent. It is important to find more convenient and effective drugs for prevention and treatment of plateau disease that is suitable for acute high altitude movement.SECTION I Effects of Acute Hypoxia Exercise Simulated in the Hypobaric Cabin on Cardiovascular System in Healthy Male YouthOBJECTIVE: To observe the effects of exercise on cardiac function and the change of exercise ability under acute hypoxia.METHODS: Healthy male young people aged 18-35 were recruited as volunteers.The baseline clinical data were collected on the plain and then clinical trial data were collected in a hypobaric cabin. Volunteers would do a treadmill exercise test (TET) in the cabin after 0.5 hours of depressurization from atmospheric pressure at 101 kPa to 61.6 kPa(equivalent to 4km altitude, n=67). The change of TET exercise ability, blood oxygen saturation (SpO2), arterial blood gas (ABG), heart rate (HR), blood pressure (SBP/DBP)and rate pressure product (RPP) in different TET phases both before and after the hypobaric cabin were all observed and compared.RESULTS:1. The normoxia TET result of all the volunteers was negative. The hypobaric cabin TET result of 12 volunteers showed positive (n=67), characterized by the ST segment depression, duration of more than 2 min, mainly concentrated in lead ?, ?, aVF. One volunteer showed accidental ventricular premature beats at the 2nd TET stage.2. The MET value of volunteers in the hypobaric cabin was significantly lower than that in plain (n = 67,P< 0.01).3. The SpO2 of volunteers in the hypobaric cabin before exercise (98.36 ± 1.42 vs. 83.70± 4.53) and after exercise (95.12 ± 8.16 vs. 75.81 ± 4.80) was both significantly lower than that in plain (n = 67, P < 0.01). The interaction of hypoxia and exercise on the decline of SpO2 was observed (n = 67, P < 0.01).4. While doing the TET both normoxia and hypoxia, HR, SBP and RPP gradually increased during exercise, and decreased gradually duiring the rest. The DBP gradually decreased during exercise, and gradually increased during the rest (n = 67, P < 0.01). There were significant differences in SBP / DBP at the same TET phase between the two groups(n = 67, P <0.01), while HR and RPP were only different at exercise phase (n = 67, P<0.05). The interaction of hypoxia and exercise on HR and RPP was significant (n = 67, P<0.05). There was not any significant interaction effect on SBP or DBP (n=67, P > 0.05).5.ABG results of volunteers in the hypobaric cabin post-TET compared to that of the plain baseline, the PH increased significantly and the remaining items except BEecf were significantly decreased (n = 67, P < 0.05).SECTION II The Protective Effect of Trimetazidine on Radical Plateau Military Stress in Healthy Male YouthOBJECTIVE: A prospective cohort study to observe the protective effect of trimetazidine on radical plateau hypoxia military stress.METHODS: A total of 78 volunteers were recruited and randomly divided into the placebo-controlled group (n=38) and the trimetazidine group (n=40). Each group took medicine or placebo for 7 days (20mg 3 times a day) before they fulfilled the study. They would reach the city of Ge'ermu (2.8km above sea level) the next day after leaving Beijing.Both groups would come to the test site (elevation 4km-4.5km) by road the third day morning. The test process was in accordance with the first hypobaric cabin part. Three plateau symptom score tables were filled at 2.8km, pre-TET and post-TET.RESULTS:1.TET result of control group (n=38) showed 9 positive and trimetazidine group (n=40)showed 5 positive, characterized by the ST segment depression, duration of more than 2 min, mainly concentrated in lead ?, ?, aVF. One control group volunteer showed accidental ventricular premature beats. One control group volunteer showed accidental atrial premature beats.2. The MET value of trimetazidine group (n=40) was significantly higher than that of the control group (n=38, P < 0.05)3.SpO2 of each intragroup after exercise was significantly lower than that before exercise (P < 0.01). SpO2 before exercise had no significant difference compared between the two groups. Trimetazidine group SpO2 after exercise was slightly lower than the control group, but the difference was not significant. The interaction effect of trimetazidine and exercise on SpO2 was not significant (P > 0.05).4. The HR, SBP and RPP of the two groups were significantly increased during exercise and significantly decreased during rest (P <0.01). The DBP decreased significantly during the TET exercise and significantly increased during rest (P <0.01). Compared with the control group, the trimetazidine group HR was a little lower than that of the control group,but with no significant difference (P > 0.05). There was no significant interaction between trimetazidine and exercise on the HR of the two groups (P > 0.05). There was no significant difference in the SBP, DBP and RPP of same TET phases (P> 0.05). Interaction between trimetazidine and exercise on SBP, DBP and RPP was not significant (P> 0.05).5.There was no significant difference in the results of ABG between trimetazidine group (n=40) and control group (n=38, P > 0.05).6. The incidence of AMS and the symptoms such as headache, wheezing and palpitation were gradually increased after acelerating 4 km -4.5 km altitude from 2.8 km. The AMS and symptoms of Post-TET were significantly severe compaired to that of 2.8km (n=38, P<0.0125). Fatigue / weakness,gastrointestinal reactions,bloating, mobility decline and dyspnea were slightly increased but with no significant difference (P> 0.05). Trimetazidine had a certain effect on the symptoms of AMS and altitude sickness,but the difference was not significant (P> 0.05).SECTION ? Myocardial Injury Caused by Acute Hypoxia Exercise Stress Simulated in the Hypobaric Cabin and Protection by Trimetazidine in RatsOBJECTIVE: To explore myocardial injury caused by acute hypoxia exercise and the protective effect of trimetazidine in cellular and molecular levels.METHODS: Acute hypoxia exercise stress animal model was established by simulating hypoxia in a hypobaric cabin (61.6kPa, 4km) and passive runner (18m / min).The treatment rats were treated with trimetazidine as an intervention drug. A total of 64 male SD rats were randomly divided into 8 groups: ? control group (NC); ? drug control group (TC); ? running group (NHR); ? drug running group (THR); ?hypoxia group (NH); ? drug hypoxia group; ?hypoxia running group (NHR) ? drug hypoxia running group (THR). Blood samples were drawn immediately after the trial to measure the following serum marker levels: high-sensitivity C reactive protein (hs-CRP),superoxide dismutase (SOD), ischemia modified albumin (IMA), heart fatty acid-binding protein (H-FABP). Rats'hearts were shorn to make myocardial routine paraffin sections.The pathological changes of cardiomyocytes were observed by HE staining and apoptosis by TUNEL staining.RESULTS:1. Serum markers?Hs-CRP: Running group and hypoxia group were significantly higher than the control group (P < 0.05). The drug running group decreased significantly compared to the running group (P < 0.05). Hypoxia running group increased significantly compared with control group, running group and hypoxia group (P < 0.01). Drug hypoxia running group compared with hypoxia running group decreased significantly (P < 0.05).? SOD: Running group and hypoxia group were significantly lower than the control group (P < 0.05). Drug running group was higher than the running group (P < 0.05). Drug hypoxia group increased significantly compared with hypoxia group (P < 0.05). Hypoxia running group was significantly lower than the control group, running group and hypoxia group (P < 0.01). Drug hypoxia running group increased significantly compared to hypoxia running group (P < 0.05).?IMA: Running group and hypoxia group were significantly higher than the control group (P < 0.05). Drug running group decreased significantly compared with the running group (P < 0.05). Drug hypoxia group decreased significantly compared to hypoxia group(P<0.05). Hypoxia running group increased significantly compared with control group,running group and hypoxia group (P < 0.01). Drug hypoxia running group decreased significantly compared with hypoxia running group (P < 0.05).? H-FABP: Hypoxia group was significantly higher than the control group (P < 0.05).Drug hypoxia group decreased significantly compared to hypoxia group (P < 0.05).Hypoxia running group increased significantly compared with control group, running group and hypoxia group (P < 0.05). Drug hypoxia running group was significantly reduced compared with hypoxia running group (P < 0.05).2. HE stainingThe control group, the drug control group and the running group showed homogeneous morphology of myocardium. The nucleus structure was clear. The stripe and the intercalated disc were clear. Myocardial fibers were even and neat. Morphology of running group myocardial cells was good. Some cells were slightly stained. Myocardial fibers of hypoxia group arranged slight disorder, scattered a small amount of connective tissue in the middle, part of the myocardial cell sarcoplasmic coagulated, appeared some vacuoles. Myocardial fibers of drug hypoxia group were slightly disorder and it's morphological slightly better than the control group. Myocardial fibers of hypoxia running group arranged in a wavy wave, sarcoplasmic cohesion, the formation of red dye, different thickness of the transverse band with part of the nucleus shrank or even dissolved. The morphology of myocardial fibers in drug hypoxia running group was slightly better than that in the hypoxia group. The morphological changes of myocardium in the hypoxia running group were the most severe among the 8 groups. Trimeptrazine had a protective effect on the injury of myocardial cells.3. The apoptosis index calculated by TUNEL stainingThe apoptosis index of hypoxia group was significantly higher than the control group,but was significantly lower than drug hypoxia group (P < 0.05). Hypoxia running group was significantly higher than other groups (P < 0.01) while lower than drug hypoxia running group significantly (P < 0.01). Drug running group was slightly higher than the control group, slightly below the running group, but no significant difference (P > 0.05).CONCLUSIONS:1 .Hypoxia significantly reduces exercise tolerance. Exercise and hypoxia have interactive effects on HR, BP and RPP. Exercise can enhance the adverse effects of hypoxia on HR, BP and RPP. The incidence of AMS increased significantly during acute hypoxia exercise. Myocardial ischemia caused by acute hypoxia exercise mainly manifests as ?, ?, aVF lead ST segment depression.2 .Trimetazidine has a protective effect on acute plateau hypoxia exercise and cardiovascular system. It can significantly improve exercise tolerance. Trimetazidine also decreases myocardial ischemic changes and does not affect HR, BP and RPP during exercise.3. Exercise increases the stress response of rats' myocardium caused by acute hypoxia,causing myocardial cell injury and apoptosis. Trimetazidine can protect the stress injury caused by acute hypoxia exercise to a certain extent. |
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