前列腺素E_1与风湿性心脏病并肺动脉高压
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摘要
目的：观察前列腺素E1(PGE1)对风湿性心脏瓣膜病(风心瓣膜病)并肺动脉高压病血流动力学和血浆一氧化氮(NO)、内皮素(ET)和降钙素基因相关肽(CGRD)的影响。方法：32例入院准备瓣膜置换术风心瓣膜病病人分为二组：A组16例(肺动脉高压组)，B组16例(非肺动脉高压组)。16例健康对照组为C组。用Swan-Ganz漂浮导管监测A组用PGE1前后血流动力学变化；用放射免疫分析法检测血浆ET和CGRP浓度；镀铜镉还原法测定血清NO2-/NO3-(反映NO水平)浓度。结果：风心瓣膜病瓣膜人血浆中ET和NO浓度高于健康人，而CGRP浓度相反。风心瓣膜病瓣膜人中肺动脉高压组血浆ET浓度与肺动脉平均压力成正相关，其ET浓度显著高于非肺动脉高压组，而CGRP和NO浓度无明显差异。
PGE1能显著改变风心瓣膜病瓣膜人肺动脉高压组血流动力学参数和血浆中ET、NO和CGRP的浓度。结论：风心瓣膜病瓣膜患者血浆中ET、NO和CGRP比例失衡与肺动脉高压和局部血管内皮细胞损伤有关，还参与心力衰竭的病理生理，PGE1能抑制上述改变，它在风心瓣膜病瓣膜并肺动脉高压围手术期具有理想的药理作用和临床效果
Objective： to observe hemodynamic and alterations the levels of plasma ET, NO and CGRP after prostaglandin E1 (PGE1)administration in patients with rheumatic heart disease(RHD)associated with pulmonary hypertension. Methods：The 32 valve replacement cases with rheumatic heart
disease were collected and divided two groups: group A was 16 patients with pulmonary hypertension, group B was patients without pulmonary hypertension. Group C was16 cases who were normal controls. Group A, 20 cases whose pulmonary hemodynamic alterations were monitored with Swan-Ganz catheter, ET and CGRP level were determined by using radioimmunoassay, NO2-/NO3- (reflecting NO level) was altermined by copper coated with calmiucm reduction method. Results：The plasma both ET and NO level of patients with rheumatic heart disease were significantly higher than that of normal controls(Group C), the plasma CGRP level was on the contrary. The plasma ET level of group A was significantly higher than that of group B. The plasma level of ET had a significantly positive correlation with pulmonary arterial pressure. The hemodynamics and levels fo plasma ET, NO and CGRP took the significantly change after PGE1 in group B. Conclusion： ET, NO and CGRP might be involved in RHD by causing pulmonary hypertension and local vascular endthalium pertutarbation. PGE1 could play important roles in the perioperative valve replacement of RHD associated with pulmonary hypertension
PGE1能显著改变风心瓣膜病瓣膜人肺动脉高压组血流动力学参数和血浆中ET、NO和CGRP的浓度。结论：风心瓣膜病瓣膜患者血浆中ET、NO和CGRP比例失衡与肺动脉高压和局部血管内皮细胞损伤有关，还参与心力衰竭的病理生理，PGE1能抑制上述改变，它在风心瓣膜病瓣膜并肺动脉高压围手术期具有理想的药理作用和临床效果
Objective： to observe hemodynamic and alterations the levels of plasma ET, NO and CGRP after prostaglandin E1 (PGE1)administration in patients with rheumatic heart disease(RHD)associated with pulmonary hypertension. Methods：The 32 valve replacement cases with rheumatic heart
disease were collected and divided two groups: group A was 16 patients with pulmonary hypertension, group B was patients without pulmonary hypertension. Group C was16 cases who were normal controls. Group A, 20 cases whose pulmonary hemodynamic alterations were monitored with Swan-Ganz catheter, ET and CGRP level were determined by using radioimmunoassay, NO2-/NO3- (reflecting NO level) was altermined by copper coated with calmiucm reduction method. Results：The plasma both ET and NO level of patients with rheumatic heart disease were significantly higher than that of normal controls(Group C), the plasma CGRP level was on the contrary. The plasma ET level of group A was significantly higher than that of group B. The plasma level of ET had a significantly positive correlation with pulmonary arterial pressure. The hemodynamics and levels fo plasma ET, NO and CGRP took the significantly change after PGE1 in group B. Conclusion： ET, NO and CGRP might be involved in RHD by causing pulmonary hypertension and local vascular endthalium pertutarbation. PGE1 could play important roles in the perioperative valve replacement of RHD associated with pulmonary hypertension
引文
1罗军,朱晓东,萧明等.围手术期瓣膜替换术死因及相关死因素分析. 中国胸心血管外科杂志,1996;12(6):330-332
2朱晓东,薛淦兴主编.心脏外科指南.北京:世界图书出版公司.1990:153
3 Gaston B,Drazen JM, Loscalzo T, et al. The biology of nitrogen oxides in the airways. Am Rev Respir Dis,1994;149(2):538-541
4 Arai k.The intrapulmonary metabolism of prostaglandin E1 in patients with pulmonary hypertension.Masui,1995;36:829~834
5 Miyata M,Ueno Y,Sekine H et al.Protecive effect of beraprost sodium a stable prostacyclin analogue,In development of monocrotaline-inducedpulmonary pulmonary hypertonsion.J-Cardiovasc-Pharmacol,1996;27:20-26
6 Pans S,Xiao M,Liu Y.Hemodynamic effects of prostaglandin E1 in patients with congenital heart diease and pulmonary hypertension.Chung Hua Wai Ko Tsa Chih,1996;34:276-279
7 Spencer H.Pathology of the lung. Forth edition,1985;666：132-133
8 蒋迎九,李朝先.继发于风湿性心脏病的肺动脉高压症.重庆医科大学学报,1998;23(4):431-433
9程瑞,胡建国,吴忠仕.先天性心脏病肺动脉高压病人血清血管内皮生长因子的研究。中华胸心血管外科杂志,2000;16(6):341-42。
10 Koh E J,Lee P,Glandoman D D,et al.Pulmonary hypertension in systenmic
sclerosis and analyst of 17 patient.et al.Br-J-Rheumatol,1996;35(10):989-993.
11 汪天虎,李朝先. 肺动脉高压与风湿性心脏病肺血管组织学改变的关系. 中国胸心血管外科临床杂志,1997;4(3):184-186
12 Peacock AJ, Dawes KE, Laurent GJ. Hypoxia stimulates endothelial cell(EC) to produce a growth factor and chemoattractant for lung fibroblasts(F13). Am Rev Respir Dis,1991;143:A378
13 Heath D, Edwards JE.The pathology of hypertensive pulmonary vascular disease,circulation,1985;18:533-538
14阮英茆,朱晓东,程显声等.100例先天性心脏病肺动脉高压活检病理分级的初步探讨.中国循环杂志,1992;7(1):54-56
15 周其文,甘辉立.先天性心脏病合并肺动脉高压的诊治.中南六省胸心外科学交流会.广西, 2002,3
16 汪天虎,李朝先.风湿性二尖瓣病变心肌和肺组织的病理学观察.中国胸心血管外科临床杂志,2000;7(1):21-24
17 Yangisawa M,Kurishara H,Kimura S et al.A novel Potent vasoconstrictor peptide produced by vascular endothelial cell.Nature(lond),1988;332:411
18 Illing B, Horn M, Han H, et al. Protective effect of the specific endothelin-1 antagonist BQ610 on mechanical femetion and energy metabolism during ischemiafrefnsion injury in; solated perfused rat hearts. J Cardiovasc Pharmacol, 1996;27(4A):487-494
19 Wang QD, Li XS, Lungberg JM, et al. Protectine effects of non-peptide endothelin recepter antagonist bosentan on myocardial ischemic and reperfusion injury in the pig. Cardiorasc Res, 1995;29(6):805-812
20 Gonon AT, Wang QD, Shimizu M, et al. The novel non-peptide selective endothelin A receptor antagonist LU135. 252 protects against myocardio ischemic and reperfusion injury in the pig. Acta Physiol Scand, 1998;163(2):131-137
21 罗心平,施海明,范维虎. 一氧化氮对心功能影响的研究进展.国外医学.心血管疾病分册,1998;29(5):271-273
22张波,刘树芬,罗南萍等.肺源性心脏病急性加重期一氧化氮及肿瘤坏死因子的研究.中国危重急救医学杂志,1997;9(1):26-27
23 侯凡, 祝善俊,李隆贵等.充血性心力衰竭患者血浆一氧化氮和内皮素等的改变.中华内科杂志,1999;38(5):296-308
24 宋明英,邓世俊,庄春英.心力衰竭患者血浆中一氧化氮含量的测定及意义.中国医师杂志, 2001;3(4):300
25 Rosefeld M, Mermod J, Amara S, et al. Prduction of a novel neuropeptide by the calcitonin gene via tissuespetitic RNA processing. Nature, 1983;304(5918):129-135
26 谭建新,李岩松,黄宇戈等.CGRP对大鼠心肌缺血损伤的影响. 中国病理生理杂志,2000;16(3):226-228
27 汤健,唐朝枢.循环系统的内分泌功能.北京:北京医科大学中国协和医科大学联合出版社.1998,122-132
28 Wang X, Han C and Fiscus R. Calcitonin gene-related peptide (CGRP) causes endothelium-dependent cyclic AMP, cyclic GMP and vasorelaxant responses in rat abdominal aorAa. Neuropeptides, 1991;20:115
29 Sczeklik J, Dubiel J S, Mieczyslaw M, et al. Effects of prostaglandin E1 on pulmonary circulation in patients with pulmonary hypertension. Br Heart J, 1978;40:1397-1401
30 Friedman M, Wang SY, Sellke FW, et al. Pulmonary injury after total or partial cardiopulmonary bypass with thromboxane synthesis inhibition. Ann Thorac Surg.,1995;59:598-60
31 Katzung BG.Basic and Clinciial Pharcology.Fourth Edition London. Hall Inter Inc.1989;228-239
32 高宇翔,卿思明,欧阳川等.列腺素E1不同给药时间治疗围手术期先天性心脏病肺动脉高压的观察.中华麻醉学杂志,1999;19(6):340-342
33 Fumioto F,Arai K, Isa Y,et al.A comparative study of vasodilator effects of prostalandin E1 in patients with pulmonary hypertension after mitral valve replaccement and with adult respiatory distress syndrome. Anesth Analg,1997;85(3):507-13
34 Schmid E R, Barki C,Engel M N,et al.Inhaled nitic oxide versus intravenous vasodilators in severe pulmonary hypertension after cadiac surger.Anesth Analg,1999;89(5):1108-1115.
35 Ono S ,Janita T,Hoshikawa Y,et al.Effects of prostaglandin E1 on pulmonary
hypertension and lung vascular remodeling in a rat monocrotaline model of human puimonary hypertension.Nippon Kyobu Shikkan Gakkai Zasshi,1995;33(8):862-867
36 巩性军,李守先,张彦恩等.前列腺素E1 在先心病重度肺动脉高压中的应用.中华胸心血管外科杂志,1997;13(6):333-335
37 郭振辉,叶芩,景炳文等.不同剂量前列腺素E1对肺动脉高压的作用. 中华内科杂志,1993;32(9):591-593
38 Tritapepe L,vocip,cogliati AA, et al.Successful weaning from cardiopulmonary bypass with central venous prostaglandin E1 and left artria no repinephrine infusion in patiens with acute pulmonary hypertension. Crit Care Meel,1999 Oct;27(10):2180-2183
39 Sato K,Kosakai H, Kumabe S,t al.Ventricular septal defect with pulmonary hypertension and concomitanleft atrial myxoma in elder patient:a successfal surgical case report.Kyobu-Geka.2000;53(2):148-151.
40 Booke M,Van Aken H,Theilmerier G,et al.Prostaglandin in patients with pulmonary hypertension :The route of adminstration..Aneth Analg,1998,Apr;86(4):917-921.
41 Abe K,sakakibara Y,Miyamoto Y, et al.Effect of prostaglandin E1 on pulmonary hypertension after protamine injection during cardiac surgery.Eur J cling pharmacol,1998;54(1):21-25.
42 李小丛,李朝先,向小勇.风湿性心脏瓣膜置换术中鱼精蛋白的中毒反应的救治.中国急救医学杂志,2001;21(10):618
43 Michale N, D'Ambra, M.D,Paul J, et al. A new therpy for refractory right heart
failure and pulmonary hypertension after mitral valve replacement. J Thorac cardiovasc Surg,1985;89:567-572
44 Aneler Franco-Cereceela. Prostaglandins and CGRP release from carohacsensory nerves. Naunyn-Schmie-debergs Arch. Pharmacol,1989;340:180-184
45 谭敦勇.降钙素基因相关肽拮抗内皮素生物学效应与内皮素结合位点下调.心肺血管病杂志,2000,19(1):56-57
46 孙脊峰,焦凯,赵柏山等.前列腺素E1对慢性肾功能衰竭者肾血流肾血浆内皮素及降钙素基因相关肽的影响.中华肾病杂志,2001;17(2)：132-133
47 李小丛,李朝先,向小勇等.前列腺素E1在重症风湿性心脏病并肺动脉高压围手术期应用.中国综合临床杂志, 2002;18(1):61-62
48 赵康丽,刘迎龙.心脏外科危重病人过度反应研究现状.中华胸心血管外科杂志,20001;17(6):341-42。
49 毛斌,周其文,韦华等.体外循环后肺损伤及其炎症反应.中华胸心血管外科杂志,2000;16(4):225-227
2朱晓东,薛淦兴主编.心脏外科指南.北京:世界图书出版公司.1990:153
3 Gaston B,Drazen JM, Loscalzo T, et al. The biology of nitrogen oxides in the airways. Am Rev Respir Dis,1994;149(2):538-541
4 Arai k.The intrapulmonary metabolism of prostaglandin E1 in patients with pulmonary hypertension.Masui,1995;36:829~834
5 Miyata M,Ueno Y,Sekine H et al.Protecive effect of beraprost sodium a stable prostacyclin analogue,In development of monocrotaline-inducedpulmonary pulmonary hypertonsion.J-Cardiovasc-Pharmacol,1996;27:20-26
6 Pans S,Xiao M,Liu Y.Hemodynamic effects of prostaglandin E1 in patients with congenital heart diease and pulmonary hypertension.Chung Hua Wai Ko Tsa Chih,1996;34:276-279
7 Spencer H.Pathology of the lung. Forth edition,1985;666：132-133
8 蒋迎九,李朝先.继发于风湿性心脏病的肺动脉高压症.重庆医科大学学报,1998;23(4):431-433
9程瑞,胡建国,吴忠仕.先天性心脏病肺动脉高压病人血清血管内皮生长因子的研究。中华胸心血管外科杂志,2000;16(6):341-42。
10 Koh E J,Lee P,Glandoman D D,et al.Pulmonary hypertension in systenmic
sclerosis and analyst of 17 patient.et al.Br-J-Rheumatol,1996;35(10):989-993.
11 汪天虎,李朝先. 肺动脉高压与风湿性心脏病肺血管组织学改变的关系. 中国胸心血管外科临床杂志,1997;4(3):184-186
12 Peacock AJ, Dawes KE, Laurent GJ. Hypoxia stimulates endothelial cell(EC) to produce a growth factor and chemoattractant for lung fibroblasts(F13). Am Rev Respir Dis,1991;143:A378
13 Heath D, Edwards JE.The pathology of hypertensive pulmonary vascular disease,circulation,1985;18:533-538
14阮英茆,朱晓东,程显声等.100例先天性心脏病肺动脉高压活检病理分级的初步探讨.中国循环杂志,1992;7(1):54-56
15 周其文,甘辉立.先天性心脏病合并肺动脉高压的诊治.中南六省胸心外科学交流会.广西, 2002,3
16 汪天虎,李朝先.风湿性二尖瓣病变心肌和肺组织的病理学观察.中国胸心血管外科临床杂志,2000;7(1):21-24
17 Yangisawa M,Kurishara H,Kimura S et al.A novel Potent vasoconstrictor peptide produced by vascular endothelial cell.Nature(lond),1988;332:411
18 Illing B, Horn M, Han H, et al. Protective effect of the specific endothelin-1 antagonist BQ610 on mechanical femetion and energy metabolism during ischemiafrefnsion injury in; solated perfused rat hearts. J Cardiovasc Pharmacol, 1996;27(4A):487-494
19 Wang QD, Li XS, Lungberg JM, et al. Protectine effects of non-peptide endothelin recepter antagonist bosentan on myocardial ischemic and reperfusion injury in the pig. Cardiorasc Res, 1995;29(6):805-812
20 Gonon AT, Wang QD, Shimizu M, et al. The novel non-peptide selective endothelin A receptor antagonist LU135. 252 protects against myocardio ischemic and reperfusion injury in the pig. Acta Physiol Scand, 1998;163(2):131-137
21 罗心平,施海明,范维虎. 一氧化氮对心功能影响的研究进展.国外医学.心血管疾病分册,1998;29(5):271-273
22张波,刘树芬,罗南萍等.肺源性心脏病急性加重期一氧化氮及肿瘤坏死因子的研究.中国危重急救医学杂志,1997;9(1):26-27
23 侯凡, 祝善俊,李隆贵等.充血性心力衰竭患者血浆一氧化氮和内皮素等的改变.中华内科杂志,1999;38(5):296-308
24 宋明英,邓世俊,庄春英.心力衰竭患者血浆中一氧化氮含量的测定及意义.中国医师杂志, 2001;3(4):300
25 Rosefeld M, Mermod J, Amara S, et al. Prduction of a novel neuropeptide by the calcitonin gene via tissuespetitic RNA processing. Nature, 1983;304(5918):129-135
26 谭建新,李岩松,黄宇戈等.CGRP对大鼠心肌缺血损伤的影响. 中国病理生理杂志,2000;16(3):226-228
27 汤健,唐朝枢.循环系统的内分泌功能.北京:北京医科大学中国协和医科大学联合出版社.1998,122-132
28 Wang X, Han C and Fiscus R. Calcitonin gene-related peptide (CGRP) causes endothelium-dependent cyclic AMP, cyclic GMP and vasorelaxant responses in rat abdominal aorAa. Neuropeptides, 1991;20:115
29 Sczeklik J, Dubiel J S, Mieczyslaw M, et al. Effects of prostaglandin E1 on pulmonary circulation in patients with pulmonary hypertension. Br Heart J, 1978;40:1397-1401
30 Friedman M, Wang SY, Sellke FW, et al. Pulmonary injury after total or partial cardiopulmonary bypass with thromboxane synthesis inhibition. Ann Thorac Surg.,1995;59:598-60
31 Katzung BG.Basic and Clinciial Pharcology.Fourth Edition London. Hall Inter Inc.1989;228-239
32 高宇翔,卿思明,欧阳川等.列腺素E1不同给药时间治疗围手术期先天性心脏病肺动脉高压的观察.中华麻醉学杂志,1999;19(6):340-342
33 Fumioto F,Arai K, Isa Y,et al.A comparative study of vasodilator effects of prostalandin E1 in patients with pulmonary hypertension after mitral valve replaccement and with adult respiatory distress syndrome. Anesth Analg,1997;85(3):507-13
34 Schmid E R, Barki C,Engel M N,et al.Inhaled nitic oxide versus intravenous vasodilators in severe pulmonary hypertension after cadiac surger.Anesth Analg,1999;89(5):1108-1115.
35 Ono S ,Janita T,Hoshikawa Y,et al.Effects of prostaglandin E1 on pulmonary
hypertension and lung vascular remodeling in a rat monocrotaline model of human puimonary hypertension.Nippon Kyobu Shikkan Gakkai Zasshi,1995;33(8):862-867
36 巩性军,李守先,张彦恩等.前列腺素E1 在先心病重度肺动脉高压中的应用.中华胸心血管外科杂志,1997;13(6):333-335
37 郭振辉,叶芩,景炳文等.不同剂量前列腺素E1对肺动脉高压的作用. 中华内科杂志,1993;32(9):591-593
38 Tritapepe L,vocip,cogliati AA, et al.Successful weaning from cardiopulmonary bypass with central venous prostaglandin E1 and left artria no repinephrine infusion in patiens with acute pulmonary hypertension. Crit Care Meel,1999 Oct;27(10):2180-2183
39 Sato K,Kosakai H, Kumabe S,t al.Ventricular septal defect with pulmonary hypertension and concomitanleft atrial myxoma in elder patient:a successfal surgical case report.Kyobu-Geka.2000;53(2):148-151.
40 Booke M,Van Aken H,Theilmerier G,et al.Prostaglandin in patients with pulmonary hypertension :The route of adminstration..Aneth Analg,1998,Apr;86(4):917-921.
41 Abe K,sakakibara Y,Miyamoto Y, et al.Effect of prostaglandin E1 on pulmonary hypertension after protamine injection during cardiac surgery.Eur J cling pharmacol,1998;54(1):21-25.
42 李小丛,李朝先,向小勇.风湿性心脏瓣膜置换术中鱼精蛋白的中毒反应的救治.中国急救医学杂志,2001;21(10):618
43 Michale N, D'Ambra, M.D,Paul J, et al. A new therpy for refractory right heart
failure and pulmonary hypertension after mitral valve replacement. J Thorac cardiovasc Surg,1985;89:567-572
44 Aneler Franco-Cereceela. Prostaglandins and CGRP release from carohacsensory nerves. Naunyn-Schmie-debergs Arch. Pharmacol,1989;340:180-184
45 谭敦勇.降钙素基因相关肽拮抗内皮素生物学效应与内皮素结合位点下调.心肺血管病杂志,2000,19(1):56-57
46 孙脊峰,焦凯,赵柏山等.前列腺素E1对慢性肾功能衰竭者肾血流肾血浆内皮素及降钙素基因相关肽的影响.中华肾病杂志,2001;17(2)：132-133
47 李小丛,李朝先,向小勇等.前列腺素E1在重症风湿性心脏病并肺动脉高压围手术期应用.中国综合临床杂志, 2002;18(1):61-62
48 赵康丽,刘迎龙.心脏外科危重病人过度反应研究现状.中华胸心血管外科杂志,20001;17(6):341-42。
49 毛斌,周其文,韦华等.体外循环后肺损伤及其炎症反应.中华胸心血管外科杂志,2000;16(4):225-227