| Part 1 Effects of PM2.5 on Heart Rate,Rhythm and Coronary Flow in in-vitro Hearts of Normal and Atherosclerosis RatsObjective:To explore the possible mechanism of PM2.5 inducing cardiatoxicity of atherosclerosis rats by observing effects of PM2.5 on heart rate,arrhythmia and coronary flow in normal and atherosclerosis rats.Method:36 male Wistar-kyoto(WKY) rats were randomly divided into 2 groups:normal and atherosclerosis group.The rats in normal group were fed with basic food and water.The rats in atherosclerosis group were fed with atherosclerosis diets(4%cholesterol,0.5%sodium cholate,0.2%propylthiouracil,10%leaf fat,1.25×10U/kg body cholecalciferol,85.3%basic food) and were injected with 300,000 U/kg body cholecalciferol in right legs.The rats were fed 12 weeks.After 12 weeks of atherosclerosis diets,atherosclerosis rat model were successfully made.Isolated perfused Langendorff hearts were preparated.0.25%,0.5%,1%PM2.5 acide-soluble components(ASC) solution and 10mg nifedipine were perfused respectively. Electrocardiogram(ECG) was recorded for analyzing heart rate(HR) and cardiac arrhythmias. Coronary flow(CF) was measured in baseline and after PM2.5 ASC perfusion and after nifedipine perfusion.Results:(1) PM2.5 dose-dependently decreased HR significantly.0.25%,0.5%and 1% PM2.5 decreased HR to(229.17±12.27),(180.67±8.17),(140.33±8.36)BPM,respectively,from (268.50±10.58),(269.67±7.01),(269.33±7.94)BPM in normal group and decreased HR to (223.17±10.82),(170.67±9.75),(135.50±7.94)BPM,respectively,from(274.834±13.27),(275.17±9.41),(273.50±7.79)BPM in atherosclerosis group.There were significant changes of HR between before and after PM2.5(P＜0.001).There were no significant changes between the two groups.There were no significant changes of HR after nifedipine perfusion(P＞0.05).(2) PM2.5 dose-dependently reduced CF.0.25%,0.5%and 1%PM2.5 reduced CF to(7.02±0.86),(5.25±0.87),(4.32±0.81)ml/min,respectively,from(8.82±0.87),(8.90±0.81),(8.83±0.89)ml/min in normal group and reduced CF to(6.30±1.06),(3.73±0.79),(3.23±0.72)ml/min,respectively,from(7.95±0.92),(7.92±0.81),(7.98±1.41)ml/min in atherosclerosis group.There were significant changes of CF between before and after PM2.5 (P＜0.001).CF of two groups restored after perfusing nifedipine(P＜0.001).(3) PM2.5 dose-dependently triggered cardiac arrhythmias.1%PM2.5 made ventricular tachycardia(VT) occurrence ahead of time(7.19±2.48) minutes in atherosclerosis group vs(12.83±2.79) minutes in normal group and prolonged accumulated VT time to(109.50±18.51) seconds in atherosclerosis group vs(57.67±12.96) seconds in normal group.Conclusion:(1) PM2.5 has a direct effect on cardiovascular system,independent of the effect of PM2.5 on pulmonary circulation.(2) PM2.5 decreases HR,reduces CF and triggers venticular arrhythmias in isolated perfused hearts,which may explain the increase in the incidence of ischemic heart diseases in clinic association with elevated PM2.5 exposure.(3) PM2.5 has bigger cardiotoxicity to atherosclerosis rats.PM2.5 makes atherosclerosis progress.Part 2 Experiment investigation of PM2.5 Inducing Acute Myocardial Infarction in in-vivo Atherosclerosis RatsObjiective:To explore the effects and the possible mechanism of PM2.5 causing cardiotoxicity of atherosclerosis rats by triggering acute myocardial infarction(AMI) in normal and atherosclerosis rats.Methods:40 male Wistar-kyoto(WKY) rats were randomly divided into 2 groups:normal and atherosclerosis group.Atherosclerosis rat models were successfully established by fed with atherosclerosis diets for 12 weeks.After anaesthesia by intraperitoneally injected with pentobarbitone 40mg/kg body weight,two groups rats were exposed by intratracheal instillation of PM2.5 solution 10mg/kg body weight.Heart rate(HR) was recorded in baseline(before instillation of PM2.5) and after PM2.5 exposure 1 hour.Blood pressure(BP) was measured in baseline and after PM2.5 exposure 2 hours.Blood markers:serum cardiac troponin T(cTnT), serum high sensitive C-reactive protein(hs-CRP),serum interleukin-6(IL-6),plasma D-dimer, plasma plasminogen activator inhibitor-1(PAI-1) were measured in baseline and after PM2.5 exposure 24 hours by enzyme linked immunosorbent assay and radio-immunity assay.Results:1.PM2.5 induced HR increase.HR increased to(286.05±16.87) BPM from (282.10±10.52) BPM in normal group and increased to(297.00±14.33) BPM from(291.10±9.70) BPM in atherosclerosis group.HR of two groups increased after instillating PM2.5(P＜0.01). There were significant changes of HR between two groups(P＜0.05).2.PM2.5 induced BP increase.BP increased to(108.45±9.65/95.65±10.48)mmHg from (105.50±6.58/91.65±7.00)mmHg in normal group and increased to (113.40±9.91/99.35±10.03)mmHg from(108.20±6.98/92.50±6.79)mmHg in atherosclerosis group.BP of two groups increased after instillating PM2.5(P＜0.001).There were no significant changes of BP between two groups(P＞0.05).3.PM2.5 triggered onset of AMI.2/20 rats occurred AMI in normal group and 8/20 rats occurred AMI in atherosclerosis group.4.(1) PM2.5 increased serum IL-6(P＜0.001),serum hs-CRP(P＜0.001),plasma D-dimer(P＜0.01) and plasma PAI-1(P＜0.001) concentration.(2) The serum concentration of IL-6,hs-CRP and plasma D-dimer,PAI-1 were higher in atherosclerosis group both before and after PM2.5 instillation.(3) After PM2.5 instillation,the level of plasma D-dimer and PAI-1 were significantly higher in atherosclerosis rats with AMI.The level of plasma D-dimer is(4.44±1.80)ng/dl vs (16.98±7.26)ng/dl(P＜0.01) of non-AMI vs AMI group.The level of plasma PAI-1 is (73.67±32.88) ng/dl vs(142.50±28.70 ) ng/dl(P＜0.001) of non-AMI vs AMI group.Conclusion:(1) PM2.5 short-term exposure triggers onset of AMI.AMI incidence is higher in atherosclerosis group.The atherosclerosis rats are more susceptible to PM2.5 than normal rats. (2) PM2.5 causes adverse effects on cardiovascular system by two passways:inflammation and changes of autonomic nervous function. |
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