| Objectives Through population epidemiological, explore the effects of manganese exposure on cardiovascular system and discuss the dose response relationship; Through chronic exposure, observe the effects of manganese sulfate on myocardial tissue of rats.Methods:1. To investigated the occupational hazard factors in the workplace and identified what kind of jobs may be exposured to manganese dust.The workplace total manganese dust concentration and respirable manganese dust concentration was measured three days.We collected 394 manganese exposure workers urine samples from five production workshops, all the workers were collected from Guangxi Manganese-exposed Workers Healthy Cohort (GXMEWHC). The urine manganese concentration was tested and we analyze whether the urine manganese can be used as internal exposure biomarker.According to different workplace manganese dust concentration and the workers’ occupational exposure history, we calculation the workers short-term and long-term manganese exposure levels and comparative analysis of short-term exposure and long exposure effects on workers’ cardiovascular function.2. Forty male SPF SD rats(4 weeks,20-220g) were randomly divided into 4 groups:control group (Omg/kg), low-dose group (5mg/kg), middle-dose group (15mg/kg) and high-dose group (25mg/kg),10 rats each group. Intraperitoneal injection was performed for six months, by five times each week, the rat blood pressure was measured by tail cuff method, and the heart organ index of the rats was computed. Three rats were selected from each group randomly, and the myocardial ultrastructure of the rats was observed by using transmission electron microscopy (TEM).Results1. In the study on the relationship between the manganese exposed and urine manganese. A short time sampling to get the total manganese dust short term exposure limit (STEL) in five factory were (1.16±0.68) mg/m3, (0.75±0.70) mg/m3, (0.20±0.19) mg/m3, (0.09±0.07) mg/m3, (4.46±2.78) mg/m3, there was significant difference between the five groups (P<0.05). Personal sampling to get the respirable manganese dust time weighted average (TWA) in five factory were(0.27±0.20)mg/m3,(0.10±0.05)mg/m3,(0.09±0.07) mg/m3, (0.06±0.05) mg/m3, (0.50±0.40) mg/m3, The storage and transportation workshop manganese dust concentration is highest, statistical significance of respirable manganese dust concentration was found between the first smelter factory second workshop,the second smelter, the third smelter and the storage and transportation workshop (P<0.05).In the first smelter factory firsr workshop,74 workers urine samples were collected,urine manganese concentration is 1.5～62.95 μg/L; In the first smelter factory second workshop,99 workers urine samples were collected, urine manganese concentration of 0.1～83.9μg/L; In The second smelter factory,74 workers urine samples were collected, urine manganese concentration is 0.1 110.7μg/L; In the Third smelter factory,92 workers urine samples were collected, urine manganese concentration of 0.9～118.6μg/L; In the storage and transportation workshop,55 workers urine samples were collected, urine manganese concentration of 1.0～1003.1μg/L. Statistical significance of urine manganese concentration was found in different workshop (P<0.05).2.This cohort study included 1572 subjects, the subjects systolic blood pressure (126.2±11.8) mmHg, diastolic blood pressure (79.2±8.1) mmHg,108 of them (6.9%) were diagnosed with hypertension; 73 of them(4.6%) were diagnosed with abnormal heart rate; 83 of them(5.3%) were diagnosed with Electrical conduction block; 223 workers (14.2%) were diagnosed with ST segment change,22 workers (1.4%) were diagnosed with ventricular premature beat (VPB); 59 workers (3.8%) were diagnosed with electrical axis deflection; 27 workers (1.7%) were diagnosed with Ventricular high voltage.3. In the study of the relationship between the short time Manganese exposure with the workers cardiovascular function, according to the different TWA,the workers were divided into 4 groups, the control group (TWA<0.02 mg/m3) 402workers; the low exposure group (0.02<TWA≤0.13 mg/m3) 426 workers, the middle exposure group (0.13<TWA≤0.34 mg/m3) 381 workers and the high exposure group (TWA>0.34 mg/m3) 363 workers. There was significance between the four groups of gender, age, BMI, marital status, ethnic, cultural level, smoking, drinking, systolic blood pressure, ventricular rate, and ST segment changes (P<0.05).In the multiple linear regression analysis, after adjustment for potential confounders, we found that the workers’systolic blood pressure was associated with Gender、working years and BMI, the regression coefficient and regression equation was significant (P<0.05). The regression equation as follows: y=107.67+0.17×Working Years-5.6×Gender+1.04×BMI.In the multiple linear regression analysis, after adjustment for potential confounders, we found that the workers’heart rate was associated with working years, Smoking and respirable manganese dust TWA, the regression coefficient and regression equation was significant (P<0.05). The regression equation as follows:y=71.35+0.11×WorkingYears+0.93×Smoking-3.30×Respirable Manganese Dust TWA.In the Cox regression analysis, after adjustment for potential confounders, we found that the workers’ST-segment changes was associated with manganese dust. Using the control group as the reference group, the HR increased to 1.44, (95%CI:0.88～2.37)in the low exposure group,1.86,(95%CI:1.17～3.01) in the middle exposure group and 6.90, (95%CI:4.42～10.78) in the high exposure group.4. In the study of the relationship between the long-term manganese exposure with the workers cardiovascular function, according to the different Cumulative exposure index (CEI),the workers were divided into 4 groups, the control group (CEI≤0.45 mg/m3.y) 393workers; the low exposure group (0.45 <TWA≤1.46 mg/m3.y) 394 workers, the middle exposure group (1.46< TWA≤3.60 mg/m3.y) 393 workers and the high exposure group (TWA>3.60 mg/m3.y)392 workers. There was significance between the four groups of age,working years, marital status, cultural level, smoking, ventricular rate, and ST segment changes (P<0.05).In the multiple linear regression analysis, after adjustment for potential confounders, we found that the workers’heart rate was associated with working years, Smoking and respirable manganese dust CEI, the regression coefficient and regression equation was significant (P< 0.05). The regression equation as follows:y=72.49+0.15×WorkingYears+0.97×Smoking-1.06×Respirable Manganese Dust CEI.In the Cox regression analysis, after adjustment for potential confounders, we found that the workers’ ST-segment changes was associated with manganese dust. Using the control group as the reference group, the HR increased tol.20, (95% CI:0.74～1.95)in the low exposure group,1.36,(95%CI:0.84～2.18) in the middle exposure group and 2.24, (95%CI:1.42～3.54) in the high exposure group.5. In the study of the dose-response relationship between the manganese exposure and the worker cardiovascular function. No matter short time exposure or long-term manganese exposure, the workers’heart rate is decrease when the manganese exposure increases, and it has obvious dose response relationship. However, in the short time exposure,the workers heart rate decrease more serious. So we believe that short-term manganese exposure to a greater impact on workers’ heart rate.The BMD and BMDL of worker’s short time exposure were calculated as 2.007mg/m3 and 1.415mg/m3. In addition, we also found that, No matter short time exposure or long-term manganese exposure, the incidence of ST-segment changes is increase when the manganese exposure increases, and it has obvious dose response relationship. The BMD and BMDL of worker’s short time exposure were calculated as 0.25mg/m3 and 0.23mg/m3; The BMD and BMDL of worker’s long-term exposure were calculated as 3.68 mg/m3.y and 3.21mg/m3.y.6. There was no significant of blood pressure between the experimental group and the control group (P>0.05). The heart organ indexes of the four groups were (0.24±0.10)%, (0.25±0.02)%, (0.26±0.02)% and (0.24±0.02)%. Statistical significance of heart organ indexes was found between the middle-dose group and the control group (P<0.05). Observed by TEM, we found that-different degrees of mitochondrial crest fracture or disappear, mitochondria swelling, hydropic change and myocardial fibers degeneration happened in the rats of the three exposed groups, but not the control group.Conclusions:1. Manganese exposed can cause the workers heart rate decreased and ST segment change;There was has significant dose effect relationship between manganese exposed and the workers’ heart rate and ST segment changes.2. Chronic manganese poisoning can lead to myocardial mitochondria superfine lesions, myocardial fiber damage and heart organ index change in rats. |
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