系統識別號 U0026-3011201616561300
論文名稱(中文) 肺高壓功能預後及生物指標的建立-關於改良REVEAL預測模型及內皮前體細胞
論文名稱(英文) Developments of functional prognostic and biomolecular markers for pulmonary hypertension: the modified REVEAL score and circulating endothelial progenitor cells
校院名稱 成功大學
系所名稱(中) 臨床醫學研究所
系所名稱(英) Institute of Clinical Medicine
學年度 105
學期 1
出版年 105
研究生(中文) 許志新
研究生(英文) Chih-Hsin Hsu
學號 S98961026
學位類別 博士
語文別 英文
論文頁數 112頁
口試委員 指導教授-陳志鴻
中文關鍵字 肺高壓  預測模型  實驗模型 
英文關鍵字 pulmonary hypertension  predictive model  experimental models 
中文摘要 肺高壓是一個持續進展而且會導致右心衰竭及死亡的疾病。即使近年來藥物已有進展,但預後進步仍然有限。面對肺高壓,最大的問題就是不佳的預後及不明的機轉。建立一個預後預測模型更精細的調整治療方針及建立實驗模型以供進一步的研究致病機轉及新治療都是相當重要的。
英文摘要 Pulmonary hypertension is a progressive disease and leading to right heart failure and death. Although newer treatments for pulmonary arterial hypertension have emerged, only modest functional improvement with minimal change in hemodynamic measurements have been achieved. Based on the current knowledge of PAH, the major problem is the poor prognosis and unclear mechanism. Established an adequate predictive model to adjust treatment strategy and an experimental model for deeper understanding of mechanism and new therapies are important.
In experimental models, I focus on the functional and molecular remodeling in pulmonary circulation following cessation of excessive pulmonary flow. We enrolled patients with pulmonary hypertension related to congenital left to right shunt to evaluate dynamic change following cessation of excessive flow. We demonstrated that hemodynamic, right ventricular function and daily performance improve following volume reduction. I also create an A-V fistula rat model demonstrated that normalization of pulmonary blood flow in subjects with flow-induced pulmonary hypertension reverses the remodeling in the right ventricle and pulmonary arterial circulation, and potentiates the vascular reactivity of pulmonary artery. The remodeling process of flow-induced pulmonary hypertension is most likely reversible and these changes are closely related to differentiation and switching of vascular smooth muscle cells in the pulmonary artery and modulation of tissue inflammatory cytokines. In predictive model, my study reassessed the predictive power of the REVEAL prognostic equation using exercise treadmill test in place of six-minute walk distance. The predictive power of the equation improved and supports exercise treadmill test for predicting survival in PAH using the REVEAL risk calculator. The study allows centers to utilize exercise treadmill test in place of the six-minute walk distance allow better prognostic information for their patients.
From our results, we believe that the regression of remodeling caused by pulmonary hypertension is possible. Another novel finding of this study is that qualitative enhancement of colony formation in the circulating EPCs and simultaneous and positively correlated with the patients’ daily performance. Molecular and functional changes of endothelial progenitor cells may play an important role for pulmonary artery remodeling. We adjust treatment strategy according to predictive model and aggressively control volume status in daily practice and critical care leading to improve patient’s outcome. At the same time, deeper investigation to obtain a deeper understanding of the mechanism of remodeling regression is ongoing with our experimental models.
論文目次 Chapter 1. Introduction 1
1.1 Overview of pulmonary arterial hypertension 1
1.1.1 Definition and classification of pulmonary hypertension 1
1.1.2 Pathophysiology of pulmonary arterial hypertension 3
1.1.3 Epidemiology of pulmonary arterial hypertension 7
1.1.4 Prognosis of pulmonary arterial hypertension 8
1.2 Update on management of pulmonary hypertension 9
1.2.1 Volume status and pulmonary hypertension 9
1.2.2 Current management of pulmonary arterial hypertension 11
1.2.3 Ongoing research of pulmonary arterial hypertension 15
1.3 Thesis Aims 16
1.4 Figures and Tables 18
Chapter 2. Physiological changes following flow reduction in patients with flow-induced pulmonary hypertension 22
2.1Backgrounds and Aims 22
2.2Methods 24
2.3 Results 28
2.4 Discussion 30
2.5 Figures and Tables 34
Chapter 3 Animal model of flow-induce pulmonary hypertension 41
3.1 Backgrounds and Aims 41
3.2 Methods 43
3.3 Results 47
3.4. Discussion 49
3.5 Figures 54
Chapter 4 Predictive model for pulmonary hypertension 61
4.1 Previous predictive equation and the REVEAL score 61
4.2 Modified REVEAL score with exercise treadmill test 63
4.2.1 Backgrouds and Aims 63
4.2.2 Methods 65
4.2.3 Results 68
4.2.4 Discussion 70
4.3 Figures and Tables 71
Chapter 5 Improvement in clinical practice. 75
5.1 Backgrounds and Aims 75
5.2 Method 76
5.2.1 Life modification 76
5.2.2. Treatment guideline 77
5.2.3 Critical care 78
5.3 Results 79
5.4 Figures 80
Chapter 6 General discussion, conclusion and prospects 84
6.1 Experimental findings 86
6.1.1 Changes following flow reduction in patients with flow-induced pulmonary hypertension 86
6.1.2 Animal model 87
6.1.3 Prognostic model 88
6.1.4 Clinical practice 89
6.2 Prospects 90
6.3 Figures 92
Bibliography 93
Publication lists 104
參考文獻 Abassi, Z., Nakhoul, F., Khankin, E., Reisner, S. A., & Yigla, M. (2006). Pulmonary hypertension in chronic dialysis patients with arteriovenous fistula: pathogenesis and therapeutic prospective. Curr Opin Nephrol Hypertens, 15(4), 353-360. doi: 10.1097/01.mnh.0000232874.27846.37
Alaiti, M. A., Ishikawa, M., & Costa, M. A. (2010). Bone marrow and circulating stem/progenitor cells for regenerative cardiovascular therapy. Transl Res, 156(3), 112-129. doi: 10.1016/j.trsl.2010.06.008
Ando, J., & Yamamoto, K. (2009). Vascular mechanobiology: endothelial cell responses to fluid shear stress. Circ J, 73(11), 1983-1992.
Baandrup, J. D., Markvardsen, L. H., Peters, C. D., Schou, U. K., Jensen, J. L., Magnusson, N. E., . . . Simonsen, U. (2011). Pressure load: the main factor for altered gene expression in right ventricular hypertrophy in chronic hypoxic rats. PLoS One, 6(1), e15859. doi: 10.1371/journal.pone.0015859
Badano, L. P., Ginghina, C., Easaw, J., Muraru, D., Grillo, M. T., Lancellotti, P., . . . De Vita, S. (2010). Right ventricle in pulmonary arterial hypertension: haemodynamics, structural changes, imaging, and proposal of a study protocol aimed to assess remodelling and treatment effects. Eur J Echocardiogr, 11(1), 27-37. doi: 10.1093/ejechocard/jep152
Badesch, D. B., Raskob, G. E., Elliott, C. G., Krichman, A. M., Farber, H. W., Frost, A. E., . . . McGoon, M. D. (2010). Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest, 137(2), 376-387. doi: chest.09-1140 [pii]
Benza, R. L., Miller, D. P., Gomberg-Maitland, M., Frantz, R. P., Foreman, A. J., Coffey, C. S., . . . McGoon, M. D. (2010). Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation, 122(2), 164-172. doi: 10.1161/CIRCULATIONAHA.109.898122
Bonnet, S., Michelakis, E. D., Porter, C. J., Andrade-Navarro, M. A., Thebaud, B., Haromy, A., . . . Archer, S. L. (2006). An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension. Circulation, 113(22), 2630-2641. doi: CIRCULATIONAHA.105.609008 [pii]
Bronicki, R. A., & Baden, H. P. (2010). Pathophysiology of right ventricular failure in pulmonary hypertension. Pediatr Crit Care Med, 11(2 Suppl), S15-22. doi: 10.1097/PCC.0b013e3181c7671c
Buus, C. L., Pourageaud, F., Fazzi, G. E., Janssen, G., Mulvany, M. J., & De Mey, J. G. (2001). Smooth muscle cell changes during flow-related remodeling of rat mesenteric resistance arteries. Circ Res, 89(2), 180-186.
Cheetham, C., Taylor, R., Burke, V., O'Driscoll, G., & Green, D. J. (2005). The 6-minute walk test does not reliably detect changes in functional capacity of patients awaiting cardiac transplantation. J Heart Lung Transplant, 24(7), 848-853. doi: 10.1016/j.healun.2004.05.012
Chen, E. P., Akhter, S. A., Bittner, H. B., Koch, W. J., Davis, R. D., & Van Trigt, P., 3rd. (1999). Molecular and functional mechanisms of right ventricular adaptation in chronic pulmonary hypertension. Ann Thorac Surg, 67(4), 1053-1058.
Chin, K. M., & Rubin, L. J. (2008). Pulmonary arterial hypertension. J Am Coll Cardiol, 51(16), 1527-1538. doi: 10.1016/j.jacc.2008.01.024
Christman, B. W., McPherson, C. D., Newman, J. H., King, G. A., Bernard, G. R., Groves, B. M., & Loyd, J. E. (1992). An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med, 327(2), 70-75. doi: 10.1056/NEJM199207093270202
Cowan, K. N., Jones, P. L., & Rabinovitch, M. (2000). Elastase and matrix metalloproteinase inhibitors induce regression, and tenascin-C antisense prevents progression, of vascular disease. J Clin Invest, 105(1), 21-34. doi: 10.1172/JCI6539
D'Alonzo, G. E., Barst, R. J., Ayres, S. M., Bergofsky, E. H., Brundage, B. H., Detre, K. M., . . . et al. (1991). Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med, 115(5), 343-349.
de Perrot, M., Granton, J. T., McRae, K., Pierre, A. F., Singer, L. G., Waddell, T. K., & Keshavjee, S. (2012). Outcome of patients with pulmonary arterial hypertension referred for lung transplantation: a 14-year single-center experience. J Thorac Cardiovasc Surg, 143(4), 910-918. doi: 10.1016/j.jtcvs.2011.08.055
Diller, G. P., van Eijl, S., Okonko, D. O., Howard, L. S., Ali, O., Thum, T., . . . Wharton, J. (2008). Circulating endothelial progenitor cells in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension. Circulation, 117(23), 3020-3030. doi: 10.1161/CIRCULATIONAHA.108.769646
Eddahibi, S., Morrell, N., d'Ortho, M. P., Naeije, R., & Adnot, S. (2002). Pathobiology of pulmonary arterial hypertension. Eur Respir J, 20(6), 1559-1572.
Faludi, R., Komocsi, A., Bozo, J., Kumanovics, G., Czirjak, L., Papp, L., & Simor, T. (2008). Isolated diastolic dysfunction of right ventricle: stress-induced pulmonary hypertension. Eur Respir J, 31(2), 475-476. doi: 10.1183/09031936.00124207
Frank, H., Mlczoch, J., Huber, K., Schuster, E., Gurtner, H. P., & Kneussl, M. (1997). The effect of anticoagulant therapy in primary and anorectic drug-induced pulmonary hypertension. Chest, 112(3), 714-721.
Fuster, V., Steele, P. M., Edwards, W. D., Gersh, B. J., McGoon, M. D., & Frye, R. L. (1984). Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation, 70(4), 580-587.
Gaine, S. (2000). Pulmonary hypertension. JAMA, 284(24), 3160-3168.
Galie, N., Badesch, D., Oudiz, R., Simonneau, G., McGoon, M. D., Keogh, A. M., . . . Rubin, L. J. (2005). Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol, 46(3), 529-535. doi: S0735-1097(05)01047-8 [pii]
Galie, N., Brundage, B. H., Ghofrani, H. A., Oudiz, R. J., Simonneau, G., Safdar, Z., . . . Response to Tadalafil Study, G. (2009). Tadalafil therapy for pulmonary arterial hypertension. Circulation, 119(22), 2894-2903. doi: 10.1161/CIRCULATIONAHA.108.839274
Galie, N., Hoeper, M. M., Humbert, M., Torbicki, A., Vachiery, J. L., Barbera, J. A., . . . Simonneau, G. (2009). Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J, 30(20), 2493-2537. doi: ehp297 [pii]
Galie, N., Humbert, M., Vachiery, J. L., Gibbs, S., Lang, I., Torbicki, A., . . . Hoeper, M. (2015). 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J, 46(4), 903-975. doi: 10.1183/13993003.01032-2015
Gan, C. T., McCann, G. P., Marcus, J. T., van Wolferen, S. A., Twisk, J. W., Boonstra, A., . . . Vonk-Noordegraaf, A. (2006). NT-proBNP reflects right ventricular structure and function in pulmonary hypertension. Eur Respir J, 28(6), 1190-1194. doi: 10.1183/09031936.00016006
Ghofrani, H. A., D'Armini, A. M., Grimminger, F., Hoeper, M. M., Jansa, P., Kim, N. H., . . . Wang, C. (2013). Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med, 369(4), 319-329. doi: 10.1056/NEJMoa1209657
Ghofrani, H. A., Galie, N., Grimminger, F., Grunig, E., Humbert, M., Jing, Z. C., . . . Rubin, L. J. (2013). Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med, 369(4), 330-340. doi: 10.1056/NEJMoa1209655
Ghofrani, H. A., Voswinckel, R., Reichenberger, F., Olschewski, H., Haredza, P., Karadas, B., . . . Grimminger, F. (2004). Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: a randomized prospective study. J Am Coll Cardiol, 44(7), 1488-1496. doi: S0735-1097(04)01362-2 [pii]
Giaid, A., Yanagisawa, M., Langleben, D., Michel, R. P., Levy, R., Shennib, H., . . . Stewart, D. J. (1993). Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med, 328(24), 1732-1739. doi: 10.1056/NEJM199306173282402
Gomberg-Maitland, M. (2006). Learning to pair therapies and the expanding matrix for pulmonary arterial hypertension: Is more better? Eur Respir J., 28(4), 683-686.
Gomberg-Maitland, M., Huo, D., Benza, R. L., McLaughlin, V. V., Tapson, V. F., & Barst, R. J. (2007). Creation of a model comparing 6-minute walk test to metabolic equivalent in evaluating treatment effects in pulmonary arterial hypertension. J Heart Lung Transplant, 26(7), 732-738. doi: 10.1016/j.healun.2007.04.013
Gomberg-Maitland, M., McLaughlin, V., Gulati, M., & Rich, S. (2005). Efficacy and safety of sildenafil added to treprostinil in pulmonary hypertension. Am J Cardiol, 96(9), 1334-1336. doi: S0002-9149(05)01282-8 [pii]
Groth, A., Vrugt, B., Brock, M., Speich, R., Ulrich, S., & Huber, L. C. (2014). Inflammatory cytokines in pulmonary hypertension. Respir Res, 15, 47. doi: 10.1186/1465-9921-15-47
Gulati, M., Black, H. R., Shaw, L. J., Arnsdorf, M. F., Merz, C. N., Lauer, M. S., . . . Thisted, R. A. (2005). The prognostic value of a nomogram for exercise capacity in women. N Engl J Med, 353(5), 468-475. doi: 10.1056/NEJMoa044154
Heys, J. J., Holyoak, N., Calleja, A. M., Belohlavek, M., & Chaliki, H. P. (2010). Revisiting the simplified bernoulli equation. Open Biomed Eng J, 4, 123-128. doi: 10.2174/1874120701004010123
Hoeper, M. M., Faulenbach, C., Golpon, H., Winkler, J., Welte, T., & Niedermeyer, J. (2004). Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension. Eur Respir J, 24(6), 1007-1010. doi: 24/6/1007 [pii]
Hoeper, M. M., Markevych, I., Spiekerkoetter, E., Welte, T., & Niedermeyer, J. (2005). Goal-oriented treatment and combination therapy for pulmonary arterial hypertension. Eur Respir J, 26(5), 858-863. doi: 26/5/858 [pii]
Hoeper, M. M., Taha, N., Bekjarova, A., Gatzke, R., & Spiekerkoetter, E. (2003). Bosentan treatment in patients with primary pulmonary hypertension receiving nonparenteral prostanoids. Eur Respir J, 22(2), 330-334.
Hoffman, J. I., Rudolph, A. M., & Heymann, M. A. (1981). Pulmonary vascular disease with congenital heart lesions: pathologic features and causes. Circulation, 64(5), 873-877.
Hsu CH, G. C., Hsu HH, Chen JH. (2012). Current therapeutics for pulmonary arterial hypertension. Acta Cardiol Sin, 28, 267-278.
Hsu, C. H., Gomberg-Maitland, M., Glassner, C., & Chen, J. H. (2011). The management of pregnancy and pregnancy-related medical conditions in pulmonary arterial hypertension patients. Int J Clin Pract Suppl(172), 6-14. doi: 10.1111/j.1742-1241.2011.02711.x
Hsu CH, H. W., Huang WC, Chiu YW, Hsu TS, Kuo PH, Hsu HH,Chang JK,Cheng CC,Lai CL,Liang KW,Lin SL,Sung SH,Tsai WC,Weng KP,Hsieh KS,Yin WH,LIn SJ,Wang KY. (2014). 2014 Guidelines of Taiwan Society of Cardiology (TSOC) for the management of pulmonary arterial hypertension. Acta Cardiologica Sinica, 30, 401-444.
Humbert, M., Barst, R. J., Robbins, I. M., Channick, R. N., Galie, N., Boonstra, A., . . . Simonneau, G. (2004). Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J, 24(3), 353-359. doi: 10.1183/09031936.04.00028404
Humbert, M., Monti, G., Brenot, F., Sitbon, O., Portier, A., Grangeot-Keros, L., . . . Emilie, D. (1995). Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am J Respir Crit Care Med, 151(5), 1628-1631. doi: 10.1164/ajrccm.151.5.7735624
Humbert, M., Sitbon, O., Chaouat, A., Bertocchi, M., Habib, G., Gressin, V., . . . Simonneau, G. (2006). Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med, 173(9), 1023-1030. doi: 200510-1668OC [pii]
Humbert, M., Sitbon, O., Yaici, A., Montani, D., O'Callaghan, D. S., Jais, X., . . . French Pulmonary Arterial Hypertension, N. (2010). Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur Respir J, 36(3), 549-555. doi: 10.1183/09031936.00057010
James, K. B., Stelmach, K., Armstrong, R., Young, J. B., & Fouad-Tarazi, F. (2003). Plasma volume and outcome in pulmonary hypertension. Tex Heart Inst J, 30(4), 305-307.
Jing, Z. C., Xu, X. Q., Han, Z. Y., Wu, Y., Deng, K. W., Wang, H., . . . Yang, Y. J. (2007). Registry and survival study in chinese patients with idiopathic and familial pulmonary arterial hypertension. Chest, 132(2), 373-379. doi: 10.1378/chest.06-2913
Jones, D. A., Benjamin, C. W., & Linseman, D. A. (1995). Activation of thromboxane and prostacyclin receptors elicits opposing effects on vascular smooth muscle cell growth and mitogen-activated protein kinase signaling cascades. Mol Pharmacol, 48(5), 890-896.
Kovacs, G., Berghold, A., Scheidl, S., & Olschewski, H. (2009). Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J, 34(4), 888-894. doi: 10.1183/09031936.00145608
Mathai, S. C., Girgis, R. E., Fisher, M. R., Champion, H. C., Housten-Harris, T., Zaiman, A., & Hassoun, P. M. (2007). Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension. Eur Respir J, 29(3), 469-475. doi: 09031936.00081706 [pii]
Mathew, R., & Gewitz, M. H. (2000). Pulmonary hypertension in infancy and childhood. Heart Dis, 2(5), 362-368.
McGoon, M. D., Krichman, A., Farber, H. W., Barst, R. J., Raskob, G. E., Liou, T. G., . . . Giles, S. (2008). Design of the REVEAL registry for US patients with pulmonary arterial hypertension. Mayo Clin Proc, 83(8), 923-931. doi: 10.4065/83.8.923
McLaughlin, V. V., Archer, S. L., Badesch, D. B., Barst, R. J., Farber, H. W., Lindner, J. R., . . . Varga, J. (2009). ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol, 53(17), 1573-1619. doi: S0735-1097(09)00142-9 [pii]
McLaughlin VV, A. S., Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J; American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association. (2009). ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol, 53(17), 1573-1619.
McLaughlin, V. V., Oudiz, R. J., Frost, A., Tapson, V. F., Murali, S., Channick, R. N., . . . Rubin, L. J. (2006). Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med, 174(11), 1257-1263. doi: 200603-358OC [pii]
Morris, C. R., Morris, S. M., Jr., Hagar, W., Van Warmerdam, J., Claster, S., Kepka-Lenhart, D., . . . Vichinsky, E. P. (2003). Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med, 168(1), 63-69.
Obi, S., Yamamoto, K., Shimizu, N., Kumagaya, S., Masumura, T., Sokabe, T., . . . Ando, J. (2009). Fluid shear stress induces arterial differentiation of endothelial progenitor cells. J Appl Physiol (1985), 106(1), 203-211. doi: 10.1152/japplphysiol.00197.2008
Orr, A. W., Lee, M. Y., Lemmon, J. A., Yurdagul, A., Jr., Gomez, M. F., Bortz, P. D., & Wamhoff, B. R. (2009). Molecular mechanisms of collagen isotype-specific modulation of smooth muscle cell phenotype. Arterioscler Thromb Vasc Biol, 29(2), 225-231. doi: 10.1161/ATVBAHA.108.178749
Patterson, J. A., Naughton, J., Pietras, R. J., & Gunnar, R. M. (1972). Treadmill exercise in assessment of the functional capacity of patients with cardiac disease. Am J Cardiol, 30(7), 757-762.
Peacock, A. J., Murphy, N. F., McMurray, J. J., Caballero, L., & Stewart, S. (2007). An epidemiological study of pulmonary arterial hypertension. Eur Respir J, 30(1), 104-109. doi: 09031936.00092306 [pii]
Pearce, J. D., Li, J., Edwards, M. S., English, W. P., & Geary, R. L. (2004). Differential effects of Rho-kinase inhibition on artery wall mass and remodeling. J Vasc Surg, 39(1), 223-228. doi: 10.1016/S0741
Peter, R. H., & Rubin, L. (1984). The pharmacologic control of the pulmonary circulation in pulmonary hypertension. Adv Intern Med, 29, 495-520.
Petkov, V., Mosgoeller, W., Ziesche, R., Raderer, M., Stiebellehner, L., Vonbank, K., . . . Block, L. H. (2003). Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest, 111(9), 1339-1346. doi: 10.1172/JCI17500
Price, L. C., Wort, S. J., Finney, S. J., Marino, P. S., & Brett, S. J. (2010). Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review. Crit Care, 14(5), R169. doi: 10.1186/cc9264
Provencher, S., Jais, X., & Sitbon, O. (2005). Bosentan therapy for pulmonary arterial hypertension. Future Cardiol, 1(3), 299-309. doi: 10.1517/14796678.1.3.299
Rai, P. R., Cool, C. D., King, J. A., Stevens, T., Burns, N., Winn, R. A., . . . Voelkel, N. F. (2008). The cancer paradigm of severe pulmonary arterial hypertension. Am J Respir Crit Care Med, 178(6), 558-564. doi: 10.1164/rccm.200709-1369PP
Redington, A. N., Rigby, M. L., Shinebourne, E. A., & Oldershaw, P. J. (1990). Changes in the pressure-volume relation of the right ventricle when its loading conditions are modified. Br Heart J, 63(1), 45-49.
Rich, S., Dantzker, D. R., Ayres, S. M., Bergofsky, E. H., Brundage, B. H., Detre, K. M., . . . et al. (1987). Primary pulmonary hypertension. A national prospective study. Ann Intern Med, 107(2), 216-223.
Rich, S., Kaufmann, E., & Levy, P. S. (1992). The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med, 327(2), 76-81. doi: 10.1056/NEJM199207093270203
Rich, S., Seidlitz, M., Dodin, E., Osimani, D., Judd, D., Genthner, D., . . . Francis, G. (1998). The short-term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension. Chest, 114(3), 787-792.
Riha, G. M., Lin, P. H., Lumsden, A. B., Yao, Q., & Chen, C. (2005). Roles of hemodynamic forces in vascular cell differentiation. Ann Biomed Eng, 33(6), 772-779.
Roan, J. N., Fang, S. Y., Chang, S. W., Hsu, C. H., Huang, C. C., Chiou, M. H., . . . Lam, C. F. (2012). Rosuvastatin improves vascular function of arteriovenous fistula in a diabetic rat model. Journal of Vascular Surgery, 56(5), 1381-1389.
Roan, J. N., Fang, S. Y., Chang, S. W., Hsu, C. H., Huang, C. C., Chiou, M. H., . . . Lam, C. F. (2012). Rosuvastatin improves vascular function of arteriovenous fistula in a diabetic rat model. J Vasc Surg, 56(5), 1381-1389 e1381. doi: 10.1016/j.jvs.2012.03.243
Roan, J. N., Tsai, Y. C., Chen, I. W., Chang, S. W., Huang, C. C., & Lam, C. F. (2012). Inhibition of cyclooxygenase-2 modulates phenotypic switching of vascular smooth muscle cells during increased aortic blood flow. Heart Vessels, 27, 307-315. doi: 10.1007/s00380-011-0148-y
Roan, J. N., Yeh, C. Y., Chiu, W. C., Lee, C. H., Chang, S. W., Jiangshieh, Y. F., . . . Lam, C. F. (2011). Functional Dilatation and Medial Remodeling of the Renal Artery in Response to Chronic Increased Blood Flow. Kidney Blood Press Res, 34(6), 447-456. doi: 10.1159/000329096
Rubens, C., Ewert, R., Halank, M., Wensel, R., Orzechowski, H. D., Schultheiss, H. P., & Hoeffken, G. (2001). Big endothelin-1 and endothelin-1 plasma levels are correlated with the severity of primary pulmonary hypertension. Chest, 120(5), 1562-1569.
Rzucidlo, E. M., Martin, K. A., & Powell, R. J. (2007). Regulation of vascular smooth muscle cell differentiation. J Vasc Surg, 45 Suppl A, A25-32. doi: 10.1016/j.jvs.2007.03.001
Selimovic, N., Bergh, C. H., Andersson, B., Sakiniene, E., Carlsten, H., & Rundqvist, B. (2009). Growth factors and interleukin-6 across the lung circulation in pulmonary hypertension. Eur Respir J, 34(3), 662-668. doi: 10.1183/09031936.00174908
Shah, S. J., Thenappan, T., Rich, S., Sur, J., Archer, S. L., & Gomberg-Maitland, M. (2009). Value of exercise treadmill testing in the risk stratification of patients with pulmonary hypertension. Circ Heart Fail, 2(4), 278-286. doi: 10.1161/CIRCHEARTFAILURE.108.807826
Sharma, S., Taegtmeyer, H., Adrogue, J., Razeghi, P., Sen, S., Ngumbela, K., & Essop, M. F. (2004). Dynamic changes of gene expression in hypoxia-induced right ventricular hypertrophy. Am J Physiol Heart Circ Physiol, 286(3), H1185-1192. doi: 10.1152/ajpheart.00916.2003
Shin, D. S., Jeffrey, R. B., & Desser, T. S. (2010). Pearls and pitfalls in hepatic ultrasonography. Ultrasound Q, 26(1), 17-25. doi: 10.1097/RUQ.0b013e3181ce1537
00013644-201003000-00003 [pii]
Sievert, H., Horvath, K., Zadan, E., Krumsdorf, U., Fach, A., Merle, H., . . . Lissmann-Jensen, H. (2001). Patent foramen ovale closure in patients with transient ischemia attack/stroke. J Interv Cardiol, 14(2), 261-266.
Simon, M. A. (2010). Right ventricular adaptation to pressure overload. Curr Opin Crit Care, 16(3), 237-243. doi: 10.1097/MCC.0b013e3283382e58
Simonneau, G., Galie, N., Rubin, L. J., Langleben, D., Seeger, W., Domenighetti, G., . . . Fishman, A. (2004). Clinical classification of pulmonary hypertension. J Am Coll Cardiol, 43(12 Suppl S), 5S-12S. doi: 10.1016/j.jacc.2004.02.037
Simonneau, G., Rubin, L. J., Galie, N., Barst, R. J., Fleming, T. R., Frost, A. E., . . . Badesch, D. B. (2008). Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med, 149(8), 521-530. doi: 149/8/521 [pii]
Soon, E., Holmes, A. M., Treacy, C. M., Doughty, N. J., Southgate, L., Machado, R. D., . . . Morrell, N. W. (2010). Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension. Circulation, 122(9), 920-927. doi: 10.1161/CIRCULATIONAHA.109.933762
Steudel, W., Ichinose, F., Huang, P. L., Hurford, W. E., Jones, R. C., Bevan, J. A., . . . Zapol, W. M. (1997). Pulmonary vasoconstriction and hypertension in mice with targeted disruption of the endothelial nitric oxide synthase (NOS 3) gene. Circ Res, 81(1), 34-41.
Tan, J. L., Prati, D., Gatzoulis, M. A., Gibson, D., Henein, M. Y., & Li, W. (2007). The right ventricular response to high afterload: comparison between atrial switch procedure, congenitally corrected transposition of the great arteries, and idiopathic pulmonary arterial hypertension. Am Heart J, 153(4), 681-688. doi: 10.1016/j.ahj.2006.12.027
Thenappan, T., Shah, S. J., Rich, S., & Gomberg-Maitland, M. (2007). A USA-based registry for pulmonary arterial hypertension: 1982-2006. Eur Respir J, 30(6), 1103-1110. doi: 10.1183/09031936.00042107
Tsai, M. T., Hsu, C. H., Luo, C. Y., Hu, Y. N., & Roan, J. N. (2015). Bridge-to-recovery strategy using extracorporeal membrane oxygenation for critical pulmonary hypertension complicated with cardiogenic shock. Interact Cardiovasc Thorac Surg, 21(1), 55-61. doi: 10.1093/icvts/ivv070
Tuder, R. M., Cool, C. D., Geraci, M. W., Wang, J., Abman, S. H., Wright, L., . . . Voelkel, N. F. (1999). Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med, 159(6), 1925-1932. doi: 10.1164/ajrccm.159.6.9804054
Vlahakes, G. J., Turley, K., & Hoffman, J. I. (1981). The pathophysiology of failure in acute right ventricular hypertension: hemodynamic and biochemical correlations. Circulation, 63(1), 87-95.
Vonk-Noordegraaf, A., Marcus, J. T., Gan, C. T., Boonstra, A., & Postmus, P. E. (2005). Interventricular mechanical asynchrony due to right ventricular pressure overload in pulmonary hypertension plays an important role in impaired left ventricular filling. Chest, 128(6 Suppl), 628S-630S. doi: 10.1378/chest.128.6_suppl.628S
Watts, J. A., Marchick, M. R., & Kline, J. A. (2010). Right ventricular heart failure from pulmonary embolism: key distinctions from chronic pulmonary hypertension. J Card Fail, 16(3), 250-259. doi: 10.1016/j.cardfail.2009.11.008
Wedgwood, S., McMullan, D. M., Bekker, J. M., Fineman, J. R., & Black, S. M. (2001). Role for endothelin-1-induced superoxide and peroxynitrite production in rebound pulmonary hypertension associated with inhaled nitric oxide therapy. Circ Res, 89(4), 357-364.
Weiss, B. M., Zemp, L., Seifert, B., & Hess, O. M. (1998). Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996. J Am Coll Cardiol, 31(7), 1650-1657.
Wharton, J., Strange, J. W., Moller, G. M., Growcott, E. J., Ren, X., Franklyn, A. P., . . . Wilkins, M. R. (2005). Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med, 172(1), 105-113. doi: 200411-1587OC [pii]
Xu, M. G., Meng, X. C., Li, B. N., & Liu, C. (2013). The circulating level of endothelial progenitor cells after transcatheter closure of congenital heart disease in children. Pediatr Cardiol, 34(6), 1344-1349. doi: 10.1007/s00246-013-0647-y
Yamamoto, K., Takahashi, T., Asahara, T., Ohura, N., Sokabe, T., Kamiya, A., & Ando, J. (2003). Proliferation, differentiation, and tube formation by endothelial progenitor cells in response to shear stress. J Appl Physiol (1985), 95(5), 2081-2088. doi: 10.1152/japplphysiol.00232.2003
Yuan, J. X., & Rubin, L. J. (2005). Pathogenesis of pulmonary arterial hypertension: the need for multiple hits. Circulation, 111(5), 534-538. doi: 111/5/534 [pii]
  • 同意授權校內瀏覽/列印電子全文服務,於2016-12-08起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2016-12-08起公開。

  • 如您有疑問,請聯絡圖書館