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研究生:陳俊延
研究生(外文):Chun Yen Chen
論文名稱:濃縮空氣微粒對大鼠心跳、血壓及肺臟影響之相關研究
論文名稱(外文):Effects of concentrated particle on heart rate,blood pressure and lung in rats
指導教授:鄭尊仁鄭尊仁引用關係
指導教授(外文):Tsun-Jen Cheng
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2001
畢業學年度:89
語文別:中文
論文頁數:87
中文關鍵詞:空氣微粒濃縮空氣微粒器心跳收縮壓舒張壓肺高血壓動脈粥狀硬化支氣管肺泡灌洗液
外文關鍵詞:ambient particleconcnetratorheart ratesystolic blood pressurediastolic blood pressurepulmonary hypertensionathersclerosisbronchoalveolar lavage
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中文摘要
背景及研究目的
流行病學研究指出當空氣微粒濃度增加時,心肺疾病的罹病率及死亡率也增加。但是微粒與其引起健康危害效應間的生物機轉並不十分清楚,然而在最近人類流行病學研究顯示,在空氣污染較嚴重時期,脈搏速率、血壓增加及肺功能降低。所以我們設計三個實驗來探討濃縮空氣微粒對肺高血壓大鼠心跳及血壓影響;與對動脈粥狀硬化大鼠肺損傷之研究。
方法
實驗一
三隻已植入循環生監測器大鼠於郊區,利用微粒濃縮機進行微粒暴露實驗。大鼠被置於鼻部暴露腔進行連續三天,每天六小時暴露實驗,然後休息四天,共進行五週。第一週及第五週為過濾空氣暴露,第二、三、四週為濃縮空氣微粒暴露。心跳及血壓資料以無線電接收器收集進行分析。微粒濃度範圍為108.9至338.3 μg/m3 。
實驗二
在實驗一中,健康大鼠對微粒暴露的反應並不清楚,所以設計實驗二來了解大鼠在注射monocrotaline前、後大鼠對微粒暴露的心跳速率、血壓反應。二隻已植入循環生監測器大鼠於郊區,利用微粒濃縮機進行微粒暴露實驗。大鼠被置於鼻部暴露腔進行一週二天,每天六小時暴露實驗,共進行六週。二隻大鼠分別接受濃縮空氣微粒及過濾空氣交互暴露。前三週大鼠未接受monocrotaline注射,後三週大鼠接受monocrotaline注射。心跳及血壓資料以無線電接收器收集進行分析。微粒濃度範圍為176.6 至431.1 μg/m3 。
實驗三
十八隻大鼠分為四組於郊區,利用微粒濃縮機進行微粒暴露實驗。大鼠被置於鼻部暴露腔進行連續三天,每天六小時暴露實驗。五隻動脈粥狀硬化大鼠及五隻對照組暴露於濃縮空氣微粒;四隻動脈粥狀硬化大鼠及四隻對照組暴露於過濾空氣。大鼠於暴露後四十八小時,將其解剖病分析肺泡灌洗液內發炎指標及肺病理切片。微粒濃度範圍為87.8 至461.1 μg/m3 。
結果
實驗一
以線性混合模式分析顯示,日夜週期變化、週週期變化、進入及移出固定管、體溫、及微粒暴露均與心跳速率增加、血壓升高有關。在微粒暴露後,心跳速率立即上升,至暴露後三小時達到最高點且心跳速率每分鐘增加15下,然後逐漸下降。平均血壓上升情形與心跳速率變化類似,暴露後三小時達到最高點且平均血壓增加6 mmHg。
實驗二
2隻大鼠在未注射monocrotaline前,在進行暴露實驗第1-2週,心跳速率並無明顯日夜週期變化呈不規則變動,無法已很好數學模式來配適。以線性混合模式分析顯示,日夜週期變化、週週期變化、進入及移出固定管、體溫、及微粒暴露均與心跳速率增加、血壓升高有關。在微粒暴露後,心跳速率立即上升,至暴露後3小時達到最高點且2隻大鼠心跳速率每分鐘分別增加9及18 下,然後逐漸下降。平均血壓上升情形與心跳速率變化類似,暴露後2.5小時達到最高點且平均血壓分別增加18 及 4 mmHg。
實驗三
我們研究顯示動脈粥狀硬化大鼠與對照組暴露於濃縮空氣微粒後,支氣管肺泡灌洗液發炎細胞及LDH濃度增加,肺泡壁增厚和發炎細胞浸潤。
結論
我們實驗結果顯示空氣微粒可經由不同的生物機轉來導致心跳速率增加、血壓升高及肺部發炎。空氣微粒可能經由自主神經系統來影響心跳速率及血壓;另外空氣微粒在疾病動物及健康大鼠,可能經較慢的生物機轉,如細胞激素來引起肺發炎,不似心跳及血壓對空氣微粒刺激反應快。目前對微粒的健康危害效應並不十分清楚,將來研究須要將生物機轉作一全盤了解,已進一步能夠降低微粒所引起心肺疾病的致死率及罹病率。在本實驗中疾病動物模式選擇也相當重要,在疾病動物方面,最好選擇動物彼此間的差異較少的品種,如自發性高血壓大鼠。
Abstract
Background and purpose
Epidemiological studies have demonstrated that increased concentration of ambient particles is associated with cardiopulmonary morbidity and mortality. However, the biological plausibility of the association between PM and adverse health effect has remained unknown. Recently, increased pulse rate, blood pressure and decreased lung function were found in human studies. Three studies were conducted to investigate if ambient PM was associated with heart rate & blood pressure in pulmonary hypertension rats and with lung injury in atherosclerotic rats.
Method
Study 1
Three rats were implanted with radiotelemetry and exposed to concentrated ambient PM from suburb area, generated by air particle concentrator. Rats were restrained in nose-only chamber for 6 hours per day for 3 consecutive days, and then rested for 4 days over a period of 5 weeks. The rats selected were exposed to concentrated PM in the 2nd, 3rd, and 4th weeks and exposed to filter air in the first & final week. Heart rate and blood pressure were transmitted by remote telemetry. The particle concentration ranged between 108.9 and 338.3 μg/m3.
Study 2
The phenomenon of normal rats exposed to particle was unknown, so the second study was performed to investigate if ambient PM was associated with heart rate & blood pressure in normal and pulmonary hypertension rats. Two rats were implanted with radiotelemetry and exposed to concentrated ambient PM from suburb area, generated by air particle concentrator. Rats were restrained in nose-only chamber for 6 hours per day twice a week over a period of 6 weeks. Two normal rats were exposed simultaneously either to concentrated PM or to filter air, then alternatively over three weeks. The same two rats after monocrtaline treatment followed similar course over the following three weeks. Heart rate and blood pressure were transmitted by remote telemetry. The particle concentration ranged between 175.6 and 431.1 μg/m3.
Study3
18 rats were divided into 4 groups and exposed to concentrated ambient PM from suburb area, generated by air particle concentrator. 5 atherosclerotic rats and 5 healthy rats were exposed to concentrated PM, while 4 atherosclerotic rats and 4 healthy rats were exposed to filter air. Rats were restrained in nose-only chamber for 6 hours per day for 3 consecutive days. Bronchoalveolar lavage fluid (BALF) was obtained. Markers of lung injury and pulmonary histiology were performed at 48 hours post-PM exposure. The particle concentration ranged between 87.8 and 461.1 μg/m3.
Results
Study 1
Mixed-effect model analysis revealed that daily circardian, weekly cycle, entrance, exit, body temperature and particle were associated with an increase in heart rate and blood pressure. After PM exposure, heart rate increased immediately, reached the peak at 3rd hours of exposure with an increased 15 beats per minute and gradually declined. Mean blood pressure also followed the similar pattern with an increase of 6 mmHg at peak at 3rd hours of exposure.
Study 2
Before monocrotaline treatment, no good model was found due to the loss of daily circardian in two rats. Mixed-effect model analysis revealed that daily circardian, weekly cycle, entrance, exit, body temperature and particle were associated with an increase in heart rate and blood pressure. After monocrotaline treatment, heart rate increased immediately, reached the peak at 3rd hours of exposure with an increased 17-29 beats per minute, and gradually declined. Mean blood pressure also followed the similar pattern with an increase of 9-19 mmHg at peak at 2.5 hours of exposure.
Study 3
Our results showed that increased BALF inflammatory cells and LDH were apparent in both atheroscerlotic rats and healthy rats, following the 48 hours post- PM exposure. Concentrated PM exposure in both atherosclerotic rats and health rats caused alveolar wall thickening and infiltration of inflammatory cells. In atherosclerotic rats, no typical atherosclerotic pathological change, like foam cell infiltration was observed.
Conclusion
Our results indicated that ambient PM could cause lung inflammation, increased heart rate, and blood pressure through different mechanism. Ambient PM probably influences blood pressure and heart rate immediately through modulation of autonomic nervous system. Ambient PM may also result in lung injury in healthy rats and susceptible models through delayed mechanism, such as cytokine mechanism. Therefore, the future studies will be aimed at seeking the pathways that lead to adverse health effects. These pathways will be useful in developing potential measures to prevent cardiopulmonary mortality and morbidity in exposed population. Because susceptible humans are not available for direct study, animal models provide opportunities to explore to basic issues of susceptibility and mechanism.Susceptible animal model selection was also important. Animal model, decreased inter-individual disease variation, such as spontaneous hypertension rats, was selected for the purpose of studies.
第一章 前言5
第一節 歷史背景6
第二章 文獻回顧8
第一節 人類流行病學8
第二節 微粒健康效應15
第三節 微粒引起心血管疾病的機轉19
第三章 動物模式選擇21
第一節 肺動脈高血壓動物模式21
MONOCROTALINE21
第二節 動脈粥狀硬化動物模式22
第四章 材料與方法24
第一節 動物飼養及循環生理監視器植入24
第二節 動物實驗濃縮微粒暴露系統24
第三節 暴露時間表及信號收集25
第四節 統計分析28
第五章 結果33
第六章 討論與結論37
圖1、第一隻肺高血壓大鼠暴露濃縮空氣微粒後,其心跳及血壓觀察曲線與預估曲線圖46
圖2、第二隻肺高血壓大鼠暴露濃縮空氣微粒後,其心跳觀察曲線與預估曲線圖48
圖3、第三隻肺高血壓大鼠暴露濃縮空氣微粒後,其心跳觀察曲線與預估曲線圖49
圖4 肺高血壓大鼠在暴露濃縮空氣微粒後心跳速率隨時間變化的圖示56
圖5 肺高血壓大鼠在暴露濃縮空氣微粒後平均血壓隨時間變化的圖示56
圖6 C4大鼠在注射MCT前,心跳、平均血壓、收縮壓、舒張壓及體溫在實驗期間的圖示57
圖7 C4大鼠在注射MCT後,心跳、平均血壓、收縮壓、舒張壓及體溫在實驗期間的圖示58
圖8 C6大鼠在注射MCT前,心跳、平均血壓、收縮壓、舒張壓及體溫在實驗期間的圖示59
圖9 C6大鼠在注射MCT後,心跳、平均血壓、收縮壓、舒張壓及體溫在實驗期間的圖示60
圖10 C4大鼠於注射MCT後,暴露濃縮空氣微粒後,其心跳速率觀察曲線與預估曲線圖63
圖 11 C6大鼠於注射MCT後,暴露濃縮空氣微粒後,其心跳速率觀察曲線與預估曲線圖64
圖12 2隻大鼠(C4,C6)於注射MCT後,暴露濃縮空氣微粒後心跳速率隨時間變化的圖示65
圖13 2隻大鼠(C4,C6)於注射MCT後,暴露濃縮空氣微粒後平均血壓隨時間變化的圖示66
圖14 生理循環監視器植入且暴露於濃縮空氣微粒肺高血壓大鼠,暴露於一般空氣之肺高血壓大鼠,及暴露於一般空氣之健康大鼠肺病理切片67
圖15 以支氣管肺跑灌洗液細胞總數及各類細胞數中位數圖示70
圖16 以支氣管肺泡灌洗液細胞比例中位數圖示71
圖17支氣管肺泡灌洗液總蛋白質濃度中位數圖示72
圖18 動脈粥狀硬化大鼠與對照組之主動脈病理切片73
圖19 動脈粥狀硬化大鼠與對照組分別暴露濃縮空氣微粒及過濾空氣之肺病理切片74
表1 第1隻肺高血壓大鼠暴露濃縮空氣微粒後,心跳、平均血壓、收縮壓及舒張壓線性混合模式分析51
表2 第2隻肺高血壓大鼠暴露濃縮空氣微粒後,心跳、平均血壓、收縮壓及舒張壓線性混合迴歸模式分析52
表3 第3隻肺高血壓大鼠暴露濃縮空氣微粒後,心跳、平均血壓、收縮壓及舒張壓線性混合模式分析53
表4三隻肺高血壓大鼠暴露於濃縮空氣微粒後心跳速率之線性混合模式54
表5三隻肺高血壓大鼠暴露於濃縮空氣微粒後平均血壓之線性混合模式54
表6三隻肺高血壓大鼠暴露於濃縮空氣微粒後收縮壓之線性混合模式55
表7三隻肺高血壓大鼠暴露於濃縮空氣微粒後舒張壓之線性混合模式55
表8 C4大鼠注射MCT後,暴露於濃縮空氣微粒後心跳、平均血壓、收縮壓及舒張壓迴歸模式分析61
表9 C6大鼠注射MCT後,暴露於濃縮空氣微粒後心跳、平均血壓、收縮壓及舒張壓迴歸模式分析62
表10大鼠體重68
表11血中膽固醇濃度68
表12血中三酸甘油脂68
表13支氣管灌洗液細胞總數及各種細胞分類69
表14支氣管灌洗液總蛋白濃度及LDH濃度72
附錄一、微粒濃縮器操作說明75
附錄二、鼻部暴露腔的操作說明75
附錄三、濾紙調理說明75
附錄四、循環生理監視器植入76
附錄五、肺泡灌洗液總細胞數計數方式77
附錄六、MONOCROTALINE配製77
附錄七、微粒濃度及所含元素成分78
Logan WD , Glasg MD. Mortality in the London fog incident,1952 Lancet 1953;1:336-338
Anderson HR, Limb ES , Bland JM ,Leon AP ,Strachan DP , Bower JS. Health effects of an air pollution episode in London, December 1991 Thorax 1995;50:1188-1190
Anderson HR, Spix C, Medina S, Schouten JP, Castellsague J, Rossi G, Zmirou D, Touloumi G, Wojtyniak B, Ponka A, Bacharova L, Schwartz J, Katsouyanni K. Air pollution and daily admission for chronic obstructive pulmonary disease in 6 European cities:results from the APHEA project. Eur Respir J 1997;10:1064-1071
Samet JM, Dominici F ,Curriero FC, Coursac I,Zeger SL. Fine particulate air pollution and mortality in 20 U.S. cities,1987-1994. N. Engl. J. Med. 2000;343:1742-1749
Sunyer J, Saez M, Murillo C, Castellsague J, Martinez F, Anto JM. Air pollution and emergency room admission for chronic obstructive pulmonary disease: A 5-year study. Am. J. Epidemiol 1993;137:701-705
Castellsague J, Sunyer J, Saze M , Anto JM. Short-term association between air pollution and emergency room visits for asthma in Barcelona. Thorax 1995; 50: 1051-1056
Schwartz J, Morris R. Air pollution and hospital admissions for cardiovascular disease in Detroit, Michigan. Am. J. Epidemiol. 1995;142:23-35
Burnett RT, Dales R, Krewski D, Vincent R, Dann T, Brook JR. Associations between ambient particle sulfate and admission to Ontario hospitals for cardiac and respiratory diseases. Am. J. Epidemiol. 1995;142:15-22
Schwartz J. Particulate air pollution and chronic respiratory disease. Environ Res 1993;62:7-13
Peters A, Skorkovsky J, Kotesovec F, Brynda J, Spix C, Wichmann HE, Heinrich J. Associations between mortality and air pollution in central Europe. Environ. Health Perspect. 2000;108(4):283-287
Hwang JS, Chan CC. Air pollution effects on daily clinic visits for lower respiratory illness. Am. J. Epidemiol. In press
Morris RD, Naumova EN, Munsinghe RL. Ambient air pollution and hospitalization for congestive heart failure among elderly people in seven large U.S. cities. Am. J. of Public Health 1995;85:1361-1365
Dockery DW, Pope CA III, Xu X, Spengler JD, Ware JH, Fay ME, Ferris BG, Spiezer FA. An association between air pollution and mortality in six U.S. cities. N. Engl. J. Med. 1993;329:1753-1759
Laden F, Neas LM, Dockery DW, Schwartz J. Association of fine particulate matter from different sources with daily mortality in six U.S. cities. Environ. Health Perspect. 2000;108(10):941-947
Pope CA III,Thun MJ,Namboodiri MN, Dockery DW,Evans JS,Speizer FE,Health CW Jr. Particulate air pollution as a predictor of mortality in a prospective cohort study of U.S. adults. Am. J. Respir. Crit. Care Med. 1995;151:669-674
Pope CA III, Verrier RL, Lovett EG, Larson AC, Raizenne ME, Kanner RE, Schwartz J, Villegas GM, Gold DR, Dockery DW. Heart rate variability associated with particulate air pollution Am. Heart J. 1999;138:890-899
Liao D, Cresson J, Shy C, William R, Watts R, Zweidinger R. Daily variation of particulate air pollution and poor cardiac autonomic control in the elderly. Environ. Health. Perspect. 1999;107(7):521-525
Peters A, Liu E, Verrier RL, Schwartz J, Gold DR, Mittleman M, Baliff J, Oh JA, Allen G, Monahan K, Dockery DW. Air pollution and incidence of cardiac arrythmia. Epidemiology 2000;11:11-17
Gold DR, Litonjua A, Schwartz J, Lovett E, Larson A, Nearing B, Allen G, Verrier M, Cherry R,Verrier R. Ambient pollution and heart rate variability. Circulation 2000;101:1267-1273
Pope CA III, Dockery DW, Kanner RE, Villegas GM, Schwartz J. Oxygen Saturation, pulse rate, and particulate air pollution. A daily time-series panel study. Am. J. Respir. Crit Care Med 1999;159:365-372
Peters A, Perz S, Doring A, Stieber J, Koenig W, Wichmann H. Increase in heart rate during an air pollution episode Am. J. Epidemiol 1999;150:1094-1098
Ibald-Mulli A, Stieber J, Wichamnn H, Koenig W, Peters A. Effects of air pollution on blood pressure:A population-based approach. Am. J. Public Health 2001;91(4):571-577
Seaton A, Soutar A,Crawford V, Robert E, McNerlan S, Cherrie J, Watt M, Raymond A, Stout R. Particulate air pollution and the blood .Thorax 1999; 54 (11) :1027-1032
Seaton A, MacNee W,Donaldson K, Godden D. Particulate air pollution and acute health effect. Lancet 1995; 345: 176-178
Peters A, Doring A, Wichmann HE, Koenig W. Increased plasma viscosity during an air pollution episode: a link to mortality. Lancet 1997;349:1582-1587
Ackermann-Liebrich U,Leuenberger P,Schwartz J,Schindler C,Monn C, Bolognini G, Bongard JP, Brandli O,Domenighetti G,Elsasser S,Grize L, Karrer W, Keller R., Keller-Wossidlo H,Kunzli N,Martin BW, Medici TC, Perruchoud AP, Schoni MH,Tschopp JM,Villiger B,Wuthrich B, Zellweger JP, Zemp E. The Study on Air Pollution and Lung Disease in Adult(SAPALDIA) Team. Am. J. Reapir. Crtic Care Med 1997;155:122-129
Pope CA III, Dockery DW, Spengler JD, Raizeme ME. Respiratory health and PM10 pollution. Am Rev Respir Disease 1991;144:668-674
Gamble JF, Lewis RJ. Health and respirable particulate (PM10) air pollution: a causal or statistical association. Environ Health Perspect 1996;104:838-850
Anderson M, Svartengren M, Philipson K,Camner P. Regional human lung deposition studied by repeated investigations. J. Aersol Sci 1988;19:1121-1124
Conway JH, Morre E,Fleming JS,Holgate ST. Three dimensional imaging of lung deposition from nebuliser in moderate/severe asthmatics. Am. J. Respir. Crit Care 1997;155:899-905
Ohtoshi T, Takizawa H, Okazaki H. Diesel exhaust particles stimulate human airway epithelial cells to produce cytokines relevant to airway inflammation in vitro.J. Allergy Clin Immunol 1998;101:778-785
Terashima T, Amakawa K, Matsumaru A. Diesel exhaust particles stimulate alveolar macrophages to release TNFα and IL-6 but not GM-CSF.Am J Respir Crit Care 1998;157:A880
Gavett SH, Kelly MM, Madison SL, Dreher KL. Fine ambient air particulate matter increases lavage eosinophil numbers and IL-4 in allergic mice. Am J Respir Crit Care 1997;157: A881
Barnhart MI, Chen S, Salley SO, Puro H. Ultrastructure and morphometry of guinea pigs chronically exposed to diesel engine exhaust: six months experience. J Appl Toxicol 1981;1:88-103
White HJ, Garg BD. Early pulmonary response of that rat lung to inhalation of high concentration of diesel particles. J Appl Toxicol 1981;1:104-110
Nearing BD, Verrier RL, Skornick WA, Gazula G, Killingsworth CR, Oakberg K, Godleski JJ. Inhaled fly ash results in alteration in cardiac electrophysiologic function. Am J Respir Crit Care 1996;153:A543
Kodavanti UP, Schladweiler MC, Ledbetter AD, Watkinson WP, Campen MJ, Winsett DW, Richards JR, Crissman KM, Hatch GE, Costa DL. The spontaneously hypertensive rat as a model of human cardiovascular disease: Evidence of exacerbated cardiopulmonary injury and oxidative stress from inhaled emission particulate matter. Toxicol. Appl. Pharmacol.2000; 164:250-263
Watkinson WP, Campen MJ, Costa DL. Cardiac arrythmia induction after exposure to Residual Oil Fly Ash particles in a rodent of pulmonary hypertension. Toxicol. Sci. 1998;41:209-216
Gordon T, Nadziejko C, Schlesinger R, Chen LC. Pulmonary and cardiovascular effects of acute exposure to concentrated ambient particulate matter in rats Toxicol. Letters 1998;96.97:285-288
Kodavanti UP, Mebane R, Ledbetter A, Kratz T, McGee J, Jackson MC, Walsh L, Hilliard H, Chen BY, Richard J, Costa DL. Variable pulmonary response from exposure to concentrated ambient air particle in a rat model of chronic bronchitis. Toxicol. Sci. 2000;54:441-451
Clarke RW, Catalano PJ, Koutrakis P, Krishna GG, Sitous C, Paulauskis J, Coull B., Fergusm S, Godleski JJ. Urban air particulate inhalation alters pulmonary function and induce pulmonary inflammation in a rodent model of chronic bronchotits. Inhal. Toxicol 1999; 11: 637-656
Rudell B, Sandsrtom T, Stjernberg N, Heldman KB. Controlled diesel exhaust exposure in an exposure chamber: pulmonary effects investigated with bronchoalveolar lavage. J Aersol Sci 1990;21:S411-414
Salvi S, Blomberg A, Rudell B. Acute inflammatory response in the airways and peripheral blood following short term exposure to diesel exhaust in healthy human volunteers. Am J Respir Crit Care 1997:155:425(Abstr.)
Salvi S, Blomberg A,Semper A. Upregulation of IL-8 m-RNA following acute exposure to diesel exhaust in the bronchial tissue of healthy human subjects. Am J Respir Crit Care 1998;157:A697
Oberdorster G, Finkelstein J, Ferin J, Godleski JJ, Chang LY, Gelein R, Johnson C, Crapo JD. Ultrafine particles as a potential environmental hazard . Studies with model particles. Chest 1996;109:68S-69S
Staniford TJ,Kunkel SL, Basha MA, Chensue SW, Lynch III JP,Toews GB, Westwick J,Strieter RM. Interleukin-8 gene expression by pulmonary epithelial cell line. A model for cytokine networks in the lung. J. Clin. Invest. 1990;86:1945-1953
Marini M, Vittori E, Hollemborg J, Mattoli S. Expression of potent inflammatory cytokines, granulocyte-marcophage colony stimulating factor, and interleukin-6 and interleukin-8, in bronchial epithelial cells of patients with asthma. J Allergy Clin. Immuol. 1992;89:1001-1009
Strieter RM, Kunkel SL, Bone RC. Role of tumor necrosis factor-α in disease states and inflammation. Crit. Care Med. 1993;21:S447-463
Weisensee D, Bereiter-Hahn J, Schoepppe W, Low-Friedrich I. Effects of cytokines on the contractility of cultured cardiac myocytes. Int. J. Immunopharmacol. 1993;15:581-587
Lai CJ, Kou YR. Stimulation of vagal pulmonary Cfibers by inhaled wood smoke in rats. J. Appl. Physiol. 1998;84(1):30-36
Tsuji H, Larson MG, Venditti Jr FJ, Manders ES, Evans JC,Feldman CL, Levy D. Impact of reduced heart rate variability on risk for cardiac events.Circulation 1996;94:2850-2855
Tsuji H, Venditti Jr FJ, Manders ES, Evans JC, Larson MG, Feldman CL, Levy D. Reduced heart rate variability and mortality risk in an elderly cohort. Circulation 1994;90:878-883
Wilson DW, Segall HJ, Pan LC,Lame MW, Estep JE, Morin D. Mechanism and pathology of monocrotaline pulmonary toxicity. Crit. Rev. Toxicol 1992;22(5/6):307-325
Toddi L, Mullen M, Olley PM, Rabinovitch M.Pulmonary toxicity of monocrotaline differs at critical periods of lung development. Pediatr. Res. 1985;19:731-737
Todorovich-Hunter L, Johnson DJ,Ranger P, Keeley FW, Rabinovitch M. Altered elastin and collagen synthesis associated with progressive pulmonary hypertension induced by monocrotaline: A biochemical and ultrastructure study. Lab. Invest. 1988;58:184-195
Todorovitch-Hunter L, Dodo H, Ye C, McCready L, Keeley FW, Rabinovitch M. Increase pulmonary artery elastolytic activity in adult rats with monocrotaline-induced progressive hypertensive pulmonary vascular disease compared with infants rats with nonprogressive disease. Am. Rev. Respir. Dis. 1992;146:213-223
Merkow L, Kleinerman J. An electron microscopic study of pulmonary vasculitis induced by monocrotaline . Lab Invest. 1966;48:47
Reindel JF, Ganey PE, Wanger JG, Slocombe RF, Roth RA. Development of morphologic, hemodynamic, and biochemical changes in lung of rats given monocrotaline pyrrole. Toxicol. Appl. Pharma. 1990;106:179-200
Ye C, Rabinovitch M. Inhibition of elastolysis by SC-37698 reduces development and progression of monocrotaline pulmonary hypertension. Am. J. Physiol 1991;261:H1255-1267
Ilkiw R, Todorovitch-Hunter L, Maruyama K, Shin J, Rabinovitch M. SC-39026 a serine elastase inhibitor, prevents muscularization of peripheral arteries ,suggesting a mechanism of monocrotaline pulmonary hypertension. Circ. Res. 1989;64:814-825
Stenmark KR, Morganroth ML., Remigho LK. Alveolar inflammation and arachidonate metabolism in monocrotaline-induced pulmonary hypertension. Am. J. Physiol. 1985;261:H 859-866
Voelkel NF, Tuder RM, Bridge J, Arend WP. Interleukin-1 receptor antagonist treatment reduces pulmonary hypertension generated in rats by monocrotaline. Am. J. Respir. Cell Mol. Biol. 1994;11:664-675
Wout ZGM, Pec E A, Maggiore JA, William RH, Palicharla P, Johnston TP. Poloxamer 407-mediated changes in plasma cholesterol and triglycerides following intraperitoneal injection to rats. J. Paren. Sci. Tech. 1992;46(6):192-200
Johnston TP, Palmer WK. Mechanism of Poloxamer 407 induced hypertriglyceridemia in rats. Biochem. Pharma. 1993;46:1037-1042
Palmer WK, Emeson EE, Johnston TP. Poloxamer 407-induced atherogenesis in C57BL/6 mouse. Atherosclerosis 1998;136:115-123
Sioutas C, Kim S, Chang M. Development and evaluation of a prototype ultrafine particle concentrator. J. Aerosol. Sci 1999;30(8):1001-1017
Levy RL, White PD, Stroud WD,Hillman CC. Transient tachycardia : prognostic significance alone and in association with transient hypertension. JAMA 1945;129:585-588
Dyer AR, Persky V, Stamler J, Paul O, Shekelle RB, Berkson DM. Heart rate as a prognostic factor for coronary heart disease and mortality: findings in three Chicago epidemiological studies. Am. J. Epidemiol 1980;112:736-749
Kannel WB, Wilson P, Blair SN. Epidemiologic assessment of the role of phsical activity and fitness in the development of cardiovascular disease. Am. Heart J.1985;109:876-885
Kannel WB, Kannel P, Paffenbarger RS Jr, Cupples LA. Heart rate and cardiovascular mortality: The Framingham study. Am. Heart J. 1987; 113:1489-1494
Gillum RF, Makuc DM, Feldman JJ. Pulse rate, coronary heart disease, and death: the NHANES I epidemiological follow-up study. Am. Heart J. 1991;121:172-177
Anthanase B, Annie R, Frederique T,Michel S, Louis G. Influence of heart rate on mortality in French population: role of age, gender, and blood pressure. Hypertension 1999;33:44-52
Willich SN, Maclure M, Mittleman M,Arntz H-E, Muller JE. Sudden cardiac death: support for a role of triggering in causation. Circulation 1993;87(5):1442-1450
Braunwald E. Heart Failure. In Harrison’s Principle of Internal Medicine. (. Braunwald E, Hauser SL, Fauci AS, Longo DL, Kasper DL, and. Jameson JL. 15 th Eds.). McGraw-Hill, New York.
Goldberg RJ, Larson M, Levy D. Factors associated with survival to 75 years of age in middle-aged men and women. The Framingham study. Arch. Intern. Med. 1996;156:505-509
Levy D, Wilson P W F, Anderson K, Castelli W P .Stratifying the patient at risk from coronary disease ,new insights from Framingham study. Am. Heart J.1990;119:712
Kim JR, Kiefe CI, Liu K, Williams OD. Jacobs DR Jr. Oberman A. Heart rate and subsequent blood pressure in young adults: the CARDIA study. Hypertension. 1999; 33(2):640-6
Bassiouny HS, Zarins CK, Kadowaki MH, Glagov S. Hemodynamic stress and experimental aortoiliac athersclerosis. J. Vasc. Surg.1994;19:426-434
Beere PA, Glagov S, Zarins CK. Experimental atherosclerosis at carotid bifurcation of Cynomolgus monkey: localization, compensatory enlargement ,and the sparing effect of lowered heart rate.Atherosclerosis and thrombosis 1992;12:1245-1253
Stone PH, Godleski JJ. First step toward understnding the pathophysiologic link between air pollution and cardia mortality. Am. Heart J. 1999;138:804-807
Guyton AC, Hal J. E. Nervous regulation of the circulation and rapid control of arterial pressure in Textbook of Medical Physiology, 10th ed. W.B. Saunders Company, Philadelphia, 2000.
Pope CAIII, Dockery DW, Spengler JD, Raizenne ME. Respiratory health and PM10 pollution. A daily time-series analysis. Am.rev. Respir. Dis.1991;144(3 Pt1):668-674
Pope CAIII, Dockery DW, Schwartz J. Review of epidemiological veidence of health effects of air pollution. Inhal. Toxicol.1995;7:1-18
Bates DV. Health indices of the adverse effects of air pollution:The question of coherence.Environ. Health Perspect. 1992;79:69-72
詹長權等 微粒空氣污染健康風險評估計劃第一年期末報告 EPA-89-FA11-03-236
Kennedy T, Ghio AJ, Reed W. Copper dependent inflammation and NF-κB activation by particulate air pollution.Am. J. Respir. Cell Mol. Biol. 1998;19:366-78
Lukacs NW, Strieter RM, Kunkel SL. Leukocyte infiltration in allergy airway inflammation. Am. J. Respir. Cell Mol. Biol. 1995;13;1-6
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