肼苯哒嗪/硝酸异山梨醇酯对阿霉素致大鼠慢性心衰治疗作用的研究
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摘要
背景慢性心力衰竭(CHF)是一种复杂的临床综合征,是各种心脏病的严重阶段,也是主要的死亡原因。近年来,对心力衰竭的治疗已有很大进步,但整体上看,因心力衰竭而死亡的患者数目仍在逐步上升。通过大量的临床研究证实了ACEI和β受体阻滞剂是治疗心衰的有效药物,ACEI和β阻滞剂业已成为心衰治疗的基础用药,使心衰病人的临床预后有了极大改善。基于目前心衰的死亡率仍比较高的事实,寻找能进一步改善心力衰竭的其他药物的研究具有极其重要的意义。非洲裔美国人心衰实验(African-American Heart Failure Trial,A-HeFT)研究在标准心衰治疗的基础上加用固定剂量的肼苯哒嗪(Hydralazine,HYD)+硝酸异山梨醇酯(Isosorbide dinitrate,ISDN)复合制剂,与未用这两个药物的安慰剂组对比多项指标显示病人心力衰竭情况明显改善。由于这两个药物被传统认为是血管扩张剂,能降低血压,而在实验的受试人群中高血压所占的比例较大,这种治疗方案是否能对非高血压所致的心衰,如心肌病导致的心衰也能获得同样的效果?近年研究显示,内皮功能障碍是多种心血管疾病的危险因素,内皮功能障碍在心衰的发病过程中起着十分重要的作用。从现在研究看来,ISDN在体内主要是转变为一氧化氮(NO)起药理作用,提高NO水平。研究发现HYD是一种抗氧化剂,可清除氧自由基,减轻氧化应激反应。HYD+ISDN的作用是否由于两者通过增加NO、抗氧化,改善心衰时内皮功能紊乱起作用仍未清楚。
目的本实验旨在观察,在使用ACEI和β阻滞剂基础上加用HYD+ISDN,用以治疗阿霉素(Adriamycin,ADR)致大鼠心衰的疗效。并观察该治疗方案对大鼠心衰时内皮功能和氧自由基清除能力的影响。
方法120只Wistar大鼠随机分成两组,模型组大鼠腹腔注射ADR,空白组给予生理盐水(NS)。模型组存活大鼠再随机分为安慰剂对照组、阳性对照组、实验组,分别给予NS、ACEI+β阻滞剂、ACEI+β阻滞剂+HYD+ISDN。干预6周后,经心脏彩色超声多普勒、血清B型脑钠肽(BNP)测定、有创动脉压(IABP)、大鼠生成状况及心肌组织HE染色,以评价药物疗效。组织总NO含量、内皮型一氧化氮合成酶(eNOS)及内皮素-1(ET-1) mRNA水平(采用逆转录聚合酶链反应)和蛋白水平(蛋白免疫印记法)以评估内皮功能状况;血清和组织丙二醛(MDA)含量,以评估对体内氧自由基的清除能力。
结果⑴实验组大鼠腹腔注射ADR后,模型组左室射血分数(LVEF)均低于正常组(P<0.05),左室收缩末径(LVESD)、左室舒张末径(LVEDD)均较正常组升高(P<0.05)。⑵药物干预后,与安慰剂对照组比较,实验组与阳性对照组的LVESD、LVEDD下降(P<0.05),LVEF增加(P<0.05),BNP下降(P<0.05)。实验组较阳性对照组有好转趋势,但并没有统计学意义(P>0.05)。⑶实验组和阳性对照组存活期均长于安慰剂对照组(P<0.05),但两组间存活期没有差异(P>0.05)。⑷实验组与阳性对照组的血压没有差异(P>0.05)。⑸实验组和阳性对照组总NO量均较安慰剂对照组增高(P<0.05),实验组增高更明显(P<0.05);实验组和阳性对照组均上调了eNOS mRNA和蛋白水平(P<0.05),但两组间没有差异(P>0.05);实验组和阳性对照组治疗后,均下调了ET-1 mRNA和蛋白水平(P<0.05),但两组间没有显著性差异(P>0.05)。⑹与安慰剂对照组相比,实验组和阳性对照组都降低了组织和血清中MDA的含量(P<0.05),实验组降低更明显(P<0.05)。
结论⑴在ADR诱导的大鼠心衰模型中,在ACEI和β阻滞剂基础上加用HYD+ISDN干预6周,可观察到大鼠生存状况、心功能有改善的趋势,但是与阳性对照组相比没有统计学意义。考虑这跟观察时间较短有关。⑵HYD+ISDN治疗心衰的附加效益可能是通过增加NO的含量、清除氧自由基,改善内皮功能来起到治疗心衰的作用。
Background: Chronic heart failure (CHF) is a complex clinical syndrome. It is the severe phase of cardiovascular disease and also the primary cause of death. In recent years a great deal of progress has been made in the treatment of heart failure. But the number of deaths from heart failure still increased steadily despite the advance in treatments. A large number of clinical studies confirmed that the angiotensin-converting-enzyme inhibitors (ACEI) andβ-blockers are the effective and the basic drugs for heart failure. ACEIs andβ-blockers improved the prognosis of patients with heart failure. Based on the fact that mortality rate due to heart failure is still at a high level, how to treat heart failure more effectively is an urgent problem today. Recently, African American Heart Failure Trial(A-HeFT) confirmed notable effects of hydralazine and isosorbide dinitrate combined treatment (HYD+ISDN) in African American patients with chronic heart failure on the basis of routine therapeutic strategy. There are many patients with CHF developed from hypertension in this trial. Is the benefit due to drug's particular effect of reducing blood pressure? Does this strategy have any effect on non-hypertension-induced heart failure patients,such as cardiomyopathy? Recent studies have shown that endothelial dysfunction is a risk factor of cardiovascular disease. Endothelial dysfunction plays an important role in the pathogenesis of heart failure. ISDN is a NO donor. HYD is an antioxidant reducing oxidant stress and inhibiting the breakdown of nitric oxide.Whether HYD+ISDN improve endothelial dysfunction in heart failure mediated by nitric oxide and anti-oxidation is still unclear.
Objective:We study the effect of HYD+ISDN in rats with adriamycin-induced heart failure already treated with ACEI andβ-blocker. We also observe the effect of HYD+ISDN on endothelial function and its ability of oxygen free radical scavenging in rats with heart failure.
Methods:120 Wistar rats were randomly divided into 2 groups: control group (10) and study group (110). In the study group adriamycin (ADR) was injected intraperitoneal to create a heart failure model. 70 rats survived in the study group, and then were randomly divided into three groups: treated group (n=24), positive control group (n=23),placebo control group (n=23). Each group of rats were treated with one of the following combined drugs for 6 weeks: perindopril+bisoprolol+HYD+ISDN, perindopril+bisoprolol, normal saline. The efficacy of drugs was evaluated by echocardiography, serum B-type natriuretic peptide(BNP), invasive arterial blood pressure(IABP) and histopathological stain. Endothelial function was assessed by total NO concentration, endothelial nitric oxide synthase (eNOS) and endothelin-1(ET-1) mRNA (determined by reverse transcription polymerase chain reaction) and protein level (determined by western blot). Serum and tissue malondialdehyde was detected to decide the ability of scavenging oxygen free radicals.
Results:⑴After intraperitoneal injection of ADR, left ventricular ejection fraction(LVEF) in rats of the treated group was lower (P<0.05) and left ventricular end systolic diameter(LVESD) and left ventricular end diastolic diameter(LVEDD) were higher (P<0.05).⑵After the drugs intervention: BNP, LVESD and LVEDD decreased (P <0.05) and LVEF increased (P <0.05) in rats of both the treated group and the positive control group compared with those in placebo control group. The treated group showed a trend of improvement, but no statistic difference was found between the treated group and the positive control group.⑶The treated group and the positive control group survived longer than the placebo control group (P<0.05), but there were no significant difference between the first two groups.⑷No difference of IABP was found between the treated group and the positive control group(P>0.05).⑸Compared with the placebo control group, total NO concentration increased in the treated group and the positive control group (P<0.05). Increase in the treated group was more significant (P<0.05). The expression of eNOS mRNA and protein were up-regulated (P<0.05) and ET-1 mRNA and protein expression were down-regulated in the treated group and the positive control group (P<0.05). ET-1 mRNA, eNOS and protein expression in the positive control group and the treated group had no significant difference (P>0.05).⑹Compared with the placebo control group, the treated group and the positive control group reduced the tissue and serum of malondialdehyde (MDA) level(P<0.05). Reduction in the treated group was more significant (P<0.05).
Conclusions:⑴The use of HYD+ISDN in rats with adriamycin-induced heart failure, treated prior with ACEI andβ-blocker showed a trend of improvement on survival and cardiac function. But there were no statistical significance possibly due to short treatment duration.⑵HYD+ISDN therapy showed extra improvement of heart failure by increasing the content of NO, scavenging oxygen free radicals and improving endothelial function.
目的本实验旨在观察,在使用ACEI和β阻滞剂基础上加用HYD+ISDN,用以治疗阿霉素(Adriamycin,ADR)致大鼠心衰的疗效。并观察该治疗方案对大鼠心衰时内皮功能和氧自由基清除能力的影响。
方法120只Wistar大鼠随机分成两组,模型组大鼠腹腔注射ADR,空白组给予生理盐水(NS)。模型组存活大鼠再随机分为安慰剂对照组、阳性对照组、实验组,分别给予NS、ACEI+β阻滞剂、ACEI+β阻滞剂+HYD+ISDN。干预6周后,经心脏彩色超声多普勒、血清B型脑钠肽(BNP)测定、有创动脉压(IABP)、大鼠生成状况及心肌组织HE染色,以评价药物疗效。组织总NO含量、内皮型一氧化氮合成酶(eNOS)及内皮素-1(ET-1) mRNA水平(采用逆转录聚合酶链反应)和蛋白水平(蛋白免疫印记法)以评估内皮功能状况;血清和组织丙二醛(MDA)含量,以评估对体内氧自由基的清除能力。
结果⑴实验组大鼠腹腔注射ADR后,模型组左室射血分数(LVEF)均低于正常组(P<0.05),左室收缩末径(LVESD)、左室舒张末径(LVEDD)均较正常组升高(P<0.05)。⑵药物干预后,与安慰剂对照组比较,实验组与阳性对照组的LVESD、LVEDD下降(P<0.05),LVEF增加(P<0.05),BNP下降(P<0.05)。实验组较阳性对照组有好转趋势,但并没有统计学意义(P>0.05)。⑶实验组和阳性对照组存活期均长于安慰剂对照组(P<0.05),但两组间存活期没有差异(P>0.05)。⑷实验组与阳性对照组的血压没有差异(P>0.05)。⑸实验组和阳性对照组总NO量均较安慰剂对照组增高(P<0.05),实验组增高更明显(P<0.05);实验组和阳性对照组均上调了eNOS mRNA和蛋白水平(P<0.05),但两组间没有差异(P>0.05);实验组和阳性对照组治疗后,均下调了ET-1 mRNA和蛋白水平(P<0.05),但两组间没有显著性差异(P>0.05)。⑹与安慰剂对照组相比,实验组和阳性对照组都降低了组织和血清中MDA的含量(P<0.05),实验组降低更明显(P<0.05)。
结论⑴在ADR诱导的大鼠心衰模型中,在ACEI和β阻滞剂基础上加用HYD+ISDN干预6周,可观察到大鼠生存状况、心功能有改善的趋势,但是与阳性对照组相比没有统计学意义。考虑这跟观察时间较短有关。⑵HYD+ISDN治疗心衰的附加效益可能是通过增加NO的含量、清除氧自由基,改善内皮功能来起到治疗心衰的作用。
Background: Chronic heart failure (CHF) is a complex clinical syndrome. It is the severe phase of cardiovascular disease and also the primary cause of death. In recent years a great deal of progress has been made in the treatment of heart failure. But the number of deaths from heart failure still increased steadily despite the advance in treatments. A large number of clinical studies confirmed that the angiotensin-converting-enzyme inhibitors (ACEI) andβ-blockers are the effective and the basic drugs for heart failure. ACEIs andβ-blockers improved the prognosis of patients with heart failure. Based on the fact that mortality rate due to heart failure is still at a high level, how to treat heart failure more effectively is an urgent problem today. Recently, African American Heart Failure Trial(A-HeFT) confirmed notable effects of hydralazine and isosorbide dinitrate combined treatment (HYD+ISDN) in African American patients with chronic heart failure on the basis of routine therapeutic strategy. There are many patients with CHF developed from hypertension in this trial. Is the benefit due to drug's particular effect of reducing blood pressure? Does this strategy have any effect on non-hypertension-induced heart failure patients,such as cardiomyopathy? Recent studies have shown that endothelial dysfunction is a risk factor of cardiovascular disease. Endothelial dysfunction plays an important role in the pathogenesis of heart failure. ISDN is a NO donor. HYD is an antioxidant reducing oxidant stress and inhibiting the breakdown of nitric oxide.Whether HYD+ISDN improve endothelial dysfunction in heart failure mediated by nitric oxide and anti-oxidation is still unclear.
Objective:We study the effect of HYD+ISDN in rats with adriamycin-induced heart failure already treated with ACEI andβ-blocker. We also observe the effect of HYD+ISDN on endothelial function and its ability of oxygen free radical scavenging in rats with heart failure.
Methods:120 Wistar rats were randomly divided into 2 groups: control group (10) and study group (110). In the study group adriamycin (ADR) was injected intraperitoneal to create a heart failure model. 70 rats survived in the study group, and then were randomly divided into three groups: treated group (n=24), positive control group (n=23),placebo control group (n=23). Each group of rats were treated with one of the following combined drugs for 6 weeks: perindopril+bisoprolol+HYD+ISDN, perindopril+bisoprolol, normal saline. The efficacy of drugs was evaluated by echocardiography, serum B-type natriuretic peptide(BNP), invasive arterial blood pressure(IABP) and histopathological stain. Endothelial function was assessed by total NO concentration, endothelial nitric oxide synthase (eNOS) and endothelin-1(ET-1) mRNA (determined by reverse transcription polymerase chain reaction) and protein level (determined by western blot). Serum and tissue malondialdehyde was detected to decide the ability of scavenging oxygen free radicals.
Results:⑴After intraperitoneal injection of ADR, left ventricular ejection fraction(LVEF) in rats of the treated group was lower (P<0.05) and left ventricular end systolic diameter(LVESD) and left ventricular end diastolic diameter(LVEDD) were higher (P<0.05).⑵After the drugs intervention: BNP, LVESD and LVEDD decreased (P <0.05) and LVEF increased (P <0.05) in rats of both the treated group and the positive control group compared with those in placebo control group. The treated group showed a trend of improvement, but no statistic difference was found between the treated group and the positive control group.⑶The treated group and the positive control group survived longer than the placebo control group (P<0.05), but there were no significant difference between the first two groups.⑷No difference of IABP was found between the treated group and the positive control group(P>0.05).⑸Compared with the placebo control group, total NO concentration increased in the treated group and the positive control group (P<0.05). Increase in the treated group was more significant (P<0.05). The expression of eNOS mRNA and protein were up-regulated (P<0.05) and ET-1 mRNA and protein expression were down-regulated in the treated group and the positive control group (P<0.05). ET-1 mRNA, eNOS and protein expression in the positive control group and the treated group had no significant difference (P>0.05).⑹Compared with the placebo control group, the treated group and the positive control group reduced the tissue and serum of malondialdehyde (MDA) level(P<0.05). Reduction in the treated group was more significant (P<0.05).
Conclusions:⑴The use of HYD+ISDN in rats with adriamycin-induced heart failure, treated prior with ACEI andβ-blocker showed a trend of improvement on survival and cardiac function. But there were no statistical significance possibly due to short treatment duration.⑵HYD+ISDN therapy showed extra improvement of heart failure by increasing the content of NO, scavenging oxygen free radicals and improving endothelial function.
引文
1. Anersa P,Nadal-Ginard B.Myocyte renewal and ventricular remodling.Nature,2002,415:240-243
2. Hunt SA,et al.ACC/AHA 2005 Chronic heart failure guideline update.J Am Coll Cardiol,2005:1116-43
3. Cleland JG,Khand A,Clark A.The heart failure epidemic:exactly how big is it?Eur Heart J.2001,22(8):623-6.
4.中国医学会心血管病学分会,中华心血管病杂志编辑委员会,2007中国慢性心力衰竭诊断治疗指南。中华心血管病杂志,2007,35(12).
5. Ho KK,Anderson KM,Kannel WB,et al.Survival after the onset of congestive heart failure in Framingham Heart Study subjects.Circulation,1993:88:107-15.
6. Greenberg BJ.Treatment of heart failure:states of the art and prospectives.Cardiovascus Pharmacol,2001,38:S59-S63.
7. Greenberg BJ.Treatment of heart failure:states of the art and prospectives.Cardiovascus Pharmacol,2001,38:S59-S63.
8. Hasegawa K,Iwaikanai E,Sasayama S.Neurohormonal regulation of myocardial cell apoptosis during the development of heart failure.J Cell Physiol,2001,186:11-18.
9. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.The SOLVD Investigation [J].N Engl J Med.1991,325:293-302.
10. The CONSENSUS Trial Study Group.Effects of enalapril on mortality in severe congestive heart failure.Results of the Cooperative NorthScandinavian Enalapril Survival Study(CONSENSUS)[J].N Engl J Med.1987,316:1249-1345
11. Cohn JN,Johnson G,Ziesche S,et al.A Comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic heart failure[J].N Engl J Med.1991,325:303-310
12. Waagstein F,Bristow MR,Swedberg K.et al.Beneficial effects of metaprolol in idiopathic in dilated cardiopmyopathy.The SPIC(Italian Multicentre Cardiomyopathy Study[J].Lancet,1993,342:141-1446.
13. Di Lenarda A,De Maria R,Gavazzi A,et al.Long-term survival effect of metaprolol in dilated cardiomyopathy. The SPIC(Italian Multicentre Cardiomyopathy Study) Group[J].Heart,1998,79:337-344.
14. The Cardiac Insufficiency Bisoprolol Study II(CIBIS-II):a randomized tril [J].Lancet,1999,353:9-13.
15. Packer M,Colucci US,Sackner-Bernstein JD,et al.Double-blind,placebo-controlled study of the effects of carvedilol in patients with moderate to sever heart failure.The PRICISE Trial Prospective randomized evaluation of carvedilol on symptoms and exercise[J].Circulation,1996,94:2793-2799.
16. Hunt SA,Abraham WT,Chin MH,et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society.Circulation,2005,112(12):e154-235.
17. Winlaw DS,Smythe GA,Keogh AM,et al.Nitric Oxide production and heart failure[J].Lancet,1993,341:390.
18. Ledoux J,Gee DM,Leblanc N.Increased peripheral resisitance in heart failure:new evdence suggests an alteration in vascular smooth muscle funtion[J].Bri J Pharmacol.2003,139:1245-1248.
19. Martin SR,Emanuel K,Sears CE,et al.Are myocardial eNOS and nNOS involved in the beta-adrenergic and muscarinic regulation of inotropy?A systematic investigation.Cardiovascular Research,2006,70(1):97-106.
20. Brown GC,Borvtaite V.Nitric oxide,cytochromec and mitochondria[J].Biochem Soc Symp,1999,66:17-25.
21. Rastaldo R,Pagliaro P,Cappello S,et al.Nitric Oxide and cardiac function.Life Sciences.2007,81:779-793.
22. Thomas SR,Chen K,Keaney JF.Oxidative stress and endothelial nitric oxide bioactivity[J].Antioxid Redox Signal,2003,5(2):181-194.
23. MacCarthy PY,Grocott-Mason R,Prendergast BD,et al.Contrasting inotropic effects of endogeneous endothelin in the normal and failing human heart[J].Circulation,2000,101:143-147.
24. Prendergast BD,Anning PB,Lewis MJ,et al.Regulation of left venricular relaxation in the isolate guinen-pig heart by endogenous endothelin.Cardiovasc Res.1997;33(1):131-8.
25. Spieker LE,Mitrovic V,Noll G,et al.Acute hemodynamic and neurohumoral effects of selective ETA-receptor blockade in patients with congestive heart failure[J].J Am Coll Cardiol,2000,35:1745-1752.
26. Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med, 2004; 351: 2049-57.
27. Murad S, Tajima SPinnell SR. A paradoxical effect of hydralazine on prolyland lysyl hydroxylase activities in cultured human skin fibroblasts. Arch Biochem Biophys, 1985; 241: 356-63.
28. Bruick RK, McKnight SL. A conserved family of prolyl-4-hydroxylases that modify HIF. Science, 2001; 294: 1337-40.
29. Epstein AC, Gleadle JM, McNeill LA, et al. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell, 2001; 107: 43-54.
30. Knowles HJ, Tian YM, Mole DR, et al. Novel mechanism of action for hydralazine: induction of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and angiogenesis by inhibition of prolyl hydroxylases. Circ Res, 2004; 95: 162-9.
31. Hayakawa H, Hirata Y, Kakoki M, et al. Role of nitric oxide-cGMP pathway in adrenomedullin-induced vasodilation in the rat. Hypertension, 1999; 33: 689-93.
32. Deramaudt BM, Braunstein S, Remy P, et al. Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis. J Cell Biochem, 1998; 68: 121-7.
33. Duckers HJ, Boehm M, True AL, et al. Heme oxygenase-1 protects against vascular constriction and proliferation. Nat Med, 2001; 7: 693-8.
34. Daiber A, Mulsch A, Hink U, et al. The oxidative stress concept of nitrate tolerance and the antioxidant properties of hydralazine. Am J Cardiol, 2005; 96: 25i-36i.
35. Munzel T,Kurz S,Rajagopdan S,et al.Hydralazine prevents nitroglycerin tolerance by inhibing activation of a membrane-bound NADH oxidase[J].J Clin Invest,1996,98:1465-1470
36. Bauer JA,Fung HL.Concurrent hydralazine administration preventsnitroglycerin-induced hemodynamic tolerance in experimental heart failure[J].Circulation,1991,84:35-39
37. Gogia h,Mehra A,Parikh S,et al.Prevention of tolerance to hemodynamic effects of nitrates with concomitant use of hydraiazine in patients with chronic heart failure[J].J Am Coll Cardiol,1995,26;1575-1580
38. Cohn JN,Archibald DG,Ziesche S,et al.Effect of vasodilator therapy on mortality in chronic congestive heart failure.Results of a Veterans Administeration Cooperative Study.N Engl J Med,1986,12;314(24):1547-52.
39. Rabelo E,De Angelis K,Bock P,et al.Baroreflex sensitivity and oxidative stress in adriamycin-induced heart failure.Hypertension.2001;38(3 Pt 2):576-80.
40. Hasenfuss G. Animal model of human cardiovascular disease,heart failure and hypertrophy[J ].Cardiovasc Res,1998,39 (1):60 - 76.
41. Weinberg EO,Schoen FJ,George D,et al. Angiotensin II convertingenzyme inhibition prolongs survival and modifies the transition to heart failure in rats with pressure overload hypertrophy due to ascending aortic stenosis [J ] . Circulation,1994,90(3) :1410– 1422.
42. Armal JF,Philippe M,Laboulandine I,et al.Effect of perindopril in rat cardiac volume overload[J ].Am Heart J,1993,126 (3):776- 782.
43. Underwood RD,Aarhus LL, Heublein DM,et al.Endothelin in thoracic inferior vena caval constriction model of heart failure[J ].Am J Physiol,1992 , 263 (3):H951 - H955.
44. Wilson JR,Douglas P,Hickey WF,et al.Experimental congestive heart failure produced by rapid ventricular pacing in the dog : Cardiac effects [J ].Circulation ,1987 , 75(4) :857– 867.
45. Smith HJ, Nuttall AA. Experimental models of heart failure [ J ] .CardiovascRes,1985,19(4):181 - 186.
46. Sharov VG,Sabbah HN,Shimoyama H,et al,Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure[J].AmJ Pathol ,1996,148(1):141 - 148.
47. Sabbah HN,Shimoyama H,Kono T,et al . Effects of longterm monotheraphy with enalapril,metoprolol and digoxin on the progression of left ventricular dysfunction and dilation in dogs withreduced ejection[J].Circulation,1994,89 (6) :2852-2859.
48. Arnolde L,Mcgrath B,Cocks M,et al.Adriamycin cardiomyopathyin the rabbit:An animal model of low output cardiac failure with activation of vasoconstrictor mechanisms[J].Cardiovasc Res,1985,191(67):378 - 382.
49. Singal PK,Iliskovic N.Doxorubicin induced cardiomyopathy[J].N Engl J Med,1998,339(13) :900- 905.
50. Wallace KB.Doxorubicin-induced cardiac mitochondrionopathy.Pharmacol Toxico1.2003,93(3):105-15.
51. Minotti G,Menna P,Salvatorelli E,et a1.Anthracyclines:molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity.Pharmacol Rev.2004,56(2):185-229.
52. Matsuhisa S,Otani H,Okazaki T,et al.N-acetylcysteine abolishes the protective effect of losartan against left ventricular remodeling in cardiomyopathy hamster.Antioxidants and Redox Signaling,2008,10(12):1998-2008.
53. Elliot JF,Liu Y,Yuan ZN,et al.Autoimmune cardiomyopathy and heart block develop spontaneously in HAL-DQ8 transgenic Iabeta knockout NOD mice.Proc Natl Acad Sci USA,2003,100(23):13447-13452.
54. Cohn JN.A-HeFT,old dog,new endothelial trial.Current Issues inCardiology,2005,32(2):366-368.
55. Cohn JN,Archibald DG,Ziesche S,et al.Effect of vasodilator therapy on mortality in chronic congestive heart failure.Results of a Veterans Administeration Cooperative Study.N Engl J Med,1986,12;314(24):1547-52.
56. Cohn JN,Johnson G,Ziesche S,et al.Comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of congestive heart failure.N Engl J Med,1991,325:303-310.
57. Nakanishi K, Zhao ZQ, Vinten-Johansen J, et al. Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction. J Thorac Cardiovasc Surg, 1995; 109: 1146-54.
58. Lewis NP, Tsao PS, Rickenbacher PR, et al. Induction of nitric oxide synthase in the human cardiac allograft is associated with contractile dysfunction of the left ventricle. Circulation, 1996; 93: 720-9.
59. Oddis CV,et al.Cytokine-Stimulated nitric oxide production inhibits mitochondrial activity in ardia myocytes.Biophys Res Commun,1995;213:1002.
60. Mohan P,et al.Myocardial contractile response to nitric oxide and cGMP.Circulation,1996;93:1223-9.
61. Matsuhisa S,Otani H,Okazaki T,et al.N-acetylcysteine abolishes the protective effect of losartan against left ventricular remodeling in cardiomyopathy hamster.Antioxidants and Redox Signaling,2008,10(12):1998-2008.
62. Cutler JA,Sorlie PD,Wolz M,et al.Trends in hypertension prevalence,awarness,treatment,and control rates in United States auldts between 1988 1994 and 1999 2004.Hypertension,2008;52;818-827.
63. Ferdinand KC.Fixed-dose isosorbide dinitrate-hydralazine:raced-based cardiovascular medicine benefit or mirage?J Law Med Enthics,2008;36(3):458-63.
64. Colvin-Adams M,Taylor AL.Isosorbide dinitrate-hydralazine improves outcomes in African Americans with heart failure.Cleve Clin J Med,2007;74(3):227-34.
65. Miyamoto Y,Saito Y,Kajiyama N,et al.Endothelial nitric oxide synthase gene is positively associated with essential hypertension[J].Hypertension,1998, 32:3 8.
66. Philip I,Plantefeve G,Vuillaumier-Barrot S,et al.G894T Polymorphism in the endothelial nitric oxide synthase gene is associated with an enhanced vascular responsiveness to phenylephrine [J].Circulation,1999,99:3096-3098.
67. McNamara DM,Tam SW,et al.Endothelial nitric oxide synthase(NOS3) polymorphisms in African Americans with heart failure:result from the A-HeFT trial.J card Fail.2009;15(3):191-8.
68.许丹,孙晓江.内皮源性一氧化氮合酶基因G894T多态性与脑梗死的关联性研究.中国老年学杂志2004年4月第24卷:340-343.
69. Yoshimuca M,Yasue H,Nakayama M,et al.A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in theJapanese.Hum Genet,1998,103:65-69.
70. The Beta-blocker Evaluation of Survival Trial Investigators.A trial of the beta-blocker buciondolol in patient with advanced chronic heart failure.N Engl J Med,2001,344:1659-1667.
71. Yancy CW,Flowler MB,Collucci WS,et al.Race and respose to a drenergic blockade with carvedilol in patients with chronic heart failure.N Engl J Med,2001,344:1358-1365.
72. Braunwald E.Expanding indications for beta-blockers in heart failure.N Engl J Med,2001,344:1711-1712.
73. Ferdinand KC.Fixed-dose isosorbide dinitrate-hydralazine:Race-based cardiovascular medicine benefit or mirage?J Law Med Ethics.2008,36(3):458-63.
74. Taylor AL,Ziesche S,Clyde W,et al.Early and sustained benefit on even-free survival and heart failure hospitalization from fixed-dose eombination of isosorbide dinitrate/hydralazine:consistency across subgroups in the African-American Heart Failure Trial.Circulation,2007;115;1747-1753.
75.中国医学会心血管病学分会,中华心血管病杂志编辑委员会,2007中国慢性心力衰竭诊断治疗指南。中华心血管病杂志,2007,35(12).
76. Dickstein K,Cohen-Solal A,Filippatos G,et al.ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008.European Heart Journal,2008,29:2388-2442.
77. American College of Cardiology,Foundation/American Heart Association Task,Force on Practice Guidelines International,Society for Heart and Lung Transplanation.2009 Focused Update:ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults.J Am Coll Cardiol,2009;53:1343-1382.
78. Martin SR,Emanuel K,Sears CE,et al.Are myocardial eNOS and nNOS involved in the beta-adrenergic and muscarinic regulation of inotropy?A systematic investigation.Cardiovascular Research,2006;70(1):97-106.
79. Damy T, Ratajczak P.Increased neuronal nitric oxide synthase-derived NO production in the failing human heart.The lancet.2004,363(9418):1365-1367
80. Hlubocka Z,Umnerova V,Heller S,et al.Circulating intercellular cell adhesion molecule-1,endothelin-1 and vonWillebrand factor 2 markers of endothelialdysfunction in uncomp licated essential hypertension:the effect of treatment with ACE inhibitors[J].J Hum Hypertens,2002,16 (8):557-562.
81. Sauzeau B,Rolli-Drekinderen M,Marionneau C,et al.RhoA expression is controlled by nitric oxide through cGMP-dependent protein kinase activation.J Biol Chem,2003,278(11);9472-80.
82. Kobayashi N,Higashi T,Hara K,et al.Effects of imidapril on NOS expression and myocardial remodeling in failure heart of Dahl salt-sensitive hypertensive rats.Cardiovasculr Research,1999,44:518-526.
83. Pasini AF,Garbin U,Stranieri C,et al.Nebivolol treatment reduces serum levels of asymmetric dimethylarginine and improves endothelial dysfunction in essential hypertensive patients.Am J Hypertens;2008;21(11):1251-7.
84. Dumont D,Pinaud F,Guihot AL,et al.Alteration in flow(shear stress)-induced remodeling in rat resisitance arteries with aging:improvement by a treatment with hydralazine.Cardiovasc Res,2008,77,600-608.
85. Sati Y,Kihara M,Hashimoto T,et al.Alterations in renal endothelial nitric oxide synthase exression by salt diet in angiotensin type-1a receptor gene knockout mice.J Am Soc Nephrol,2004;15:1756-1763.
86.张勇,夏勇,李东野.中国动脉硬化杂志,2006,14(5):391-394.
87. Horinaka S,Kobayashi N,Yagi H,et al.Nicorandil but not ISDN upregulates endothelial nitric synthase expression,preventing left ventricular remodeling and degradation of cardiac function in Dahl salt-sensitive hypertensive rats with congestive heart failure.J Cardiovasc Pharmacol.2006,47(5):629-35.
88. Jiang HB,Hirohito Y,Aizo F,et al.Effect of isosorbide dinitrate on nitric oxide synthase under hypoxia.Pharmacology,2001,62:10-16.
89. Matheis G,Sherman MP,Buckberg GP,et al.Role of L-arginine nitric oxide pathway in myocardial reoxygenation injury[J].Am JPhysiol,1992,262(2Pt2);H162-H620.
90. Jones SP,Greer JJ,van Haperen R,et al.Endothelial nitric oxide synthase overexpression attenuates congestive heart failure in mice.Proc Natl Acad Sci USA,2003,15:100(8):4891-6.
91. Heymes C,Vanderbeyden M,Jean GF,et al.Endomyocardial nitric synthase and left ventricular preload reserve in dilated cardiomyopathy[J].Circulation.1998,6:5009-8016.
92.向芙莉,冯清平.高血压杂志,2005,13(11):673-675.
93. Lewis NP, Tsao PS, Rickenbacher PR, et al. Induction of nitric oxide synthase in the human cardiac allograft is associated with contractile dysfunction of the left ventricle. Circulation, 1996,93: 720-9.
94.毛志芹,许玲芳,李军,等.血浆内皮素与降钙素基因相关肽在新生儿窒息中的动态变化及其临床意义[J].中国危重病急救医学,2002,14:696-697.
95.胡咏梅,李法琦,罗羽慧等.卡维地洛对压力负荷性大鼠心室重构及ET-1 mRNA表达的影响.高血压杂志,200412,03.
96. Smith RS Jr,Agata J,Xia CF,et al.Human endothelial nitric oxide synthase gene delivery protects against cardiac remodeling and reduces oxidative stress after myocardial infarction[J].Life Sci,2005,76(21):2457-2471.
97. Wang X,Ohnishi M,Wada A,et al.Endothelin-1 promotes vascular structural remodeling during the progression of heart failure prevention of vascular remodeling using a specific endothelin-converting enzyme inhibitor[J].Life Sci.2001,69(2):2477-2488.
98. Jugdutt BI,Idikio H,Uwiera RR.Therapeutic drugs during healing after myocardial infarction modify infarct collagens and ventricular distensibility at elevated pressures.Mol Cell Biochem,2007,304(1-2):79-91.
99. Amir O,Paz H,Rogowski O,et al.Serum oxidative stress level correlates withclinical parameters in chronic systolic heart failure patients[J].Clin Cardiol,2009,32(4):199-203.
100. Pu Q,Brassard P,Javeshghani DM,et al.Effects of combined AT1 receptor antagonist/NEP inhibitor on vascular remodeling and cardiac fibrosis in SHRSP.J Hypertensi,2008,26(2):322-33.
101. Quieles JL,Huertas JR,Battino M,et al.Antioxidant nutrents and adriamycin toxicity[J].Toxicology.2002,181(1):79-95.
102.李世红,王邵军.阿霉素心脏毒性发病机制新进展[J].临床心血管杂志,2005,21(4):249-250.
103.吴其夏,余应年,卢建.自由基损伤与疾病[J].病理生理学,2003:247-269.
104. Boucke RJ,Olson RD,Brener DE,et al.The major metabolite of doxorubicin is a potent inhibitor of membrane-associated in pumpa[J].J Biol Chem,1987,262:15815-15816.
105. Liang W,Tan CY,Ang L,et al.Ramipril improves oxidative stress-related vascular endothelial dysfunction in db/db mice[J].J Physiol Sci,2008,58(6):405-11.
106. Munzel T,Kurz S,Rajagopalan S,et al.Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase.A new acion for an old drug[J].J Clin Invest,1996,15,98(6)1465-70.
107. Forstermann U.Janus-faced role of endothelial NO skynthase in vascular disease:uncoupling of oxygen reduction from NO synthesis and its pharmacological reversal.Biol Chem.2006,387(12)1521-33.
108. Rugale C,Delbosc S,Mimran A,et al.Simvastatin reverses target organ damage and oxidative stress in Angiotensin II hypertension:comparison with apocynin,tempol,and hydralazine.J Cardiovasc Pharmacol.2007,50(3)293-8.
109. Reil TD,Moore WS,Kashyap VS.The effects ofthrombosis,thrombectomy and thrombolysis on endothelial function.Eur J Endovas Surg.2000,199(2):162-8.
1. Kannel WB,Ho K,Thom T.Changing epidemiological features of cardiac failure[J].Br Heart J,1994,723-9.
2.中国医学会心血管病学分会,中华心血管病杂志编辑委员会,2007中国慢性心力衰竭诊断治疗指南。中华心血管病杂志,2007,35(12).
3. Greenberg BJ.Treatment of heart failure:states of the art and prospectives.Cardiovascus Pharmacol,2001,38:S59-S63.
4. Van Zwieten PA.Changing insights in the drug treatment of congestive heart failure.Exp Opin Invest Drugs,1995,17:186-190.
5. Cosin J,Diez J,TORIC investigators.Torasemide in chronic heart failure:results of the TORIC study[J].Eur J Heart Fail,2002,4(4):507-513.
6. Chuen JM,MacFadyen RJ.Dose-dependent association between use of loop diuretics and mortality in advanced systolic heart failure[J].Am J Cardiol,2006,98(10):1416-1417.
7. Ferguson DW.Sympathctic mechanisms in heart failure.Pathophysiological and pharmacological implications.Circulation,1993,87(suppl VII):68-75.
8. Uretsky MF,Young JB,Eden Shahidi F,et al.Randomised study assessing the effect of digoxin withdrawl in patients with mild to moderate chronic congestive heart failure;results of the PROVED Trial.J Am Coll Cardiol,1993,22,955-962.
9. Packer M,Geoghiade M,Young JB,et al.Withdrawl of digoxin from patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors.N Engl J Med,1993,329:1-7.
10. Cohn JN,Archibald DG,Ziesche S,et al.Effect of vasodilator therapy onmortality in chronic congestive heart failure.Results of a Veterans Administeration Cooperative Study.N Engl J Med,1986,12;314(24):1547-52.
11. Cohn JN,Johnson G,Ziesche S,et al.A Comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic heart failure[J].N Engl J Med.1991,325:303-310.
12. Cohn JN,Ziesche SM,Loss LE,et al.Effect of felodipine on short-term mortality in heart failure.Results of V-HeFT III.Circulation,1995,92;1-143.
13. O’Connor CM,Belkin RN,Carson PE,et al.For the PRAISE Investigators.Effect of amlodipine on mode of death in severe heart failure:The PRAISE Trial.Circulation,1995,92(suppl I):1-143.
14. Echols MR,Yancy CW.Isosorbide dinitrate-hydralazine combination therapy in African Americans with heart failure.Vascular Health and Risk Management,2006:2(4):423-431.
15. Winlaw DS,Smythe GA,Keogh AM,et al.Nitric Oxide production and heart failure[J].Lancet,1993,341:390.
16. Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med, 2004; 351: 2049-57.
17. Dickstein K,Cohen-Solal A,Filippatos G,et al.ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008:the Task Force for the diagnosis and treatment of acute and Chronic heart failure 2008 of the European Society of Cardiology Developed in Collaboration with the Heart Failure Association of the ESC(HFA) and endorsed by the European Society of Intensive Care Medicine(ESICM).Eur J Heart Fail.2008;10(10):933-89.
18. American College of Cardiology,Foundation/American Heart Association Task,Force on Practice Guidelines International,Society for Heart and LungTransplanation.2009 Focused Update:ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults.J Am Coll Cardiol,2009;53:1343-1382.
19. Paul JR,Widdop RE.Persisitent cardiovascular effect of chronic rein-angiotensin system inhibition following withdraw in adult spontaneously hypertensive rats.J Hypertens,2001,19:1393-1402.
20. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.The SOLVD Investigation [J].N Engl J Med.1991,325:293-302.
21. Cohn JN,Johnson G,Ziesche S,et al.A Comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic heart failure[J].N Engl J Med.1991,325:303-310
22. The CONSENSUS Trial Study Group.Effects of enalapril on mortality in severe congestive heart failure.Results of the Cooperative North Scandinavian Enalapril Survival Study(CONSENSUS)[J].N Engl J Med.1987,316:1249-1345.
23.中国医学会心血管病学分会,中华心血管病杂志编辑委员会,2007中国慢性心力衰竭诊断治疗指南。中华心血管病杂志,2007,35(12).
24. Pitt B,Poole-Wilson PA,Segal R,et al.Effect of losartan compared with captopril on mortality in patients with syptomatic heart failure:randomised trial-the Losartan Heart Failure Survival Study ELITE II.Lancet,2000,355(9215):1582-1587.
25. Granger CB,McMurray JJ,Yusuf S,et al.Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors:the CHARM-Alternative trial.Lancet,2003,362(9386):772-776.
26. Wong M,Staszewsky L,Latini R,et al.Valsartan benefits left ventricular structure and function in heart failure:Val-HeFT echocardiographic study.J Am Coll Cardiol,2002,40(5):970-975.
27. Lijnen P,Petrov V.Induction of cardiac fibrosis by aldosterone[J].Mol Cell Cardiol,2003,32(6):865-879.
28. Pitt B,Zannad F,Remme WJ,et al.The effect of spironolactone on morbidity and mortality in patients with severe heart failure.Randomized Aldosterone Evaluation Study Investigators.N Engl J Med,1999;341(10):709-17
29. Juurlink DN,Mamdani MM,Lee DS,et al.Rates of hyperkalemia after publication of the Randomized Aldosterone Evaluation Study.N Engl J Med.2004,351(6):543-51.
30. Wang D,Liu YH,Yang XP,et al.Role of a selective aldosterone blocker in mice with chronic heart failure[J].Card Fail,2004,10(1):67-73.
31. Pitt B,Remme W,Zannad F,et al.Eplernone,a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.N Engl J Med.2003,348(14):1309-21.
32. The Cardiac Insufficiency Bisoprolol Study II(CIBIS-II):a randomised trial.Lancet,1999;353(9146):9-13.
33. Hjalmarson A,Goldstein S,Fagerberg B,et al.Effects of controlled-release metroprolol on tota mortality,hospitalizations,and well-being in patients with heart failure.the Metoprlol CR/XL Randomized Intervention Trial in congestive heart failure(MERIT-HF).JAMA,2000;283:1295-1302.
34. Dargie HJ.Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction:the CAPRICONN randomised trial.Lancet.2001;357:1385-1390.
35. Cleland JG,Pennell DJ,Ray SG,et al.Myocardial viability as a determinant ofejection fraction response to carvedilol in patients with heart failure(CHRISTMAS trial):randomised controlled trial.Lancet,2003:362:4-21.
36. Flather MD,Shibatta MC,Coats AJ,et al.Randomized trial to determine the effect of nebivolol on mortality and cardovascular hospital admission in elderly patients with heart failure(SENIORS).Eur Heart J,2005;26:215-225.
37. Winlaw DS,Smythe GA,Keogh AM,et al.Nitric Oxide production and heart failure[J].Lancet,1993,341:390.
38. Mulder P,Boujedanini H,Richard V,et al.Selective endothelin-A versum combined endothelin-A/endothelin-B receptor blockeade in rat chronic heart failure[J].Circulation,2000,102(5):491-493.
39. Nakanishi K, Zhao ZQ, Vinten-Johansen J, et al. Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction. J Thorac Cardiovasc Surg, 1995; 109: 1146-54.
40. Ruiz-Hurtado G,Fernandez-Velasco M,Mourelle M,et al.LA419,a novel nitric oxide donor,prevent pathological cardiac remodeling in pressure-overloaded rats via endothelial nitric oxide synthase pathway regulation.Hypertension,2007;50(6):1049-56.
41. Go AS,Lee WY,Yang J,et al.Statins therapy and risks for death and hospitalization in chronic heart.JAMA,2006;296(17):2105-11.
42.赵水平.他汀类药物在慢性心力衰竭防治中的研究现状[J].中华老年心脑血管病杂志,2004,6,6:289-291.
43. Kjekshus J,Apetrei E,Barrios V,et al.Rosuvastatin in older patients with systolic heart failure.N Engl J Med,2007;357(22):2246-61.
44. Gissi-HF Investigators.Effect of rosuvastatin in patients with chronicfailure(the GISSI-HF trial):a randomised,double-blind,placebo-controlled trial.Lancet.2008;372(9645):1231-9.
45. Fenster BE,Tsao S,Rockson SG,et al.Endothelial dysfunction:Clinical strategies for treating oxidant stress[J].Am Heart J,2003,146(2):216-226.
46. Yancy CW.Treatment with B-type natriuretic peptide for chronic decopensated heart failure:insights learned from the follow-up serial infusion of nesiritide(FUSION)trial[J].Heart Fail Rev,2004,9 (3):209-16.
47. Kyrzopoulos S,Adamopoulos S,Parissis JT,et al.Levosimendan reduces plasma B-type natriuretic peptide and interleukin 6,and improves central hemodynamics in severe heart failure patients.Int J Cardiol.2005;99(3):409-13.
48. Abraham WT.Rationale and design of a randomized clinical trial to assess the safty and efficacy of cardiac resynchronization therapy in patients with advanced heart failure:the Multicenter InSync Randomized Clinical Evaluation(MIRACLE)[J].J Card Fail,2000,6(4):369-380.
49. Bristow MR,Saxon LA,Boehmer J,et al.The comparison of Medical Therapy,Pacing and Defibrillation in Heart Failure(COMPANION)Investigators.Cardiac-Resynchronization Therapy with or without an Implantable Defibrillation in Adbanced Chronic Heart Failure[J].N Engl J Med,2004,350:2140-2150.
50. Mark DB,Nelson CL,Anstron KJ,et al.Cost-effectiveness of defribrillator therapy or amiodarone in chronic stable heart failure:results from the Sudden Cardiac Death in Heart Failure Trial(SCD-HeFT)[J].Circulation,2001,114(2):135-142.
51. Young JB,Abraham WT,Smith AL,et al.Combined cardiac resynchronization and implantable cardio version defibrillator in advanced chronic heartfailure:the MIRACLE ICD trial[J].JAMA,2003,289:2685-2694.
52. Graf T.Differntiation plasticity of hematopoietic cells[J].Blood,2002,99:3089-3101.
53. Schaefer A,meyer GP,Fuchs M,et al.Impact of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction:results from the BOOTS trial[J].Eur Heart J,2006,27(8):929-935.
54. Anker SD,von Heahling S.Inflammatory mediators in chronic heart failure:an over-view[J].Heart,2004;90:464
55. Gullestad L,Aukrust P.Review of trials in chronic heart failure showing broad-spectrum anti-inflammatory approaches[J].Am J Cardiol,2005,95(suppl):17C.
56. Chung ES,Packer M,Lo KH,et al.Randomized,double-blind,placebo-cntrolled,pilot trial of infliximab,a chimeric monoclonal antibody to tumor necrosis factor-alpha,in patients with moderate-to-severe heart failure:results of anti-TNF Therapy Against Congestive Heart Failure(ATTACH)trial[J].Circulation,2003,107(25):3133.
57. Mann DL,McMurry JJ,Packer M,et al.Targeted anticytokine therapy in patients with chronic heart failure:results of the Randomized Etanercept Worldwide Evaluation(RENEWAL)[J].Circulation,2004,109(13):1594.
58. Torre-Amione G,Sestier F,Radovancevic B,et al.Effects of a novel immune modulation therapy in patients with advanced chronic heart failure:results of a randomized,controlled phaseⅡtrial[J].J Am Coll Cardiol.2004,44(6):1181-6.
59. Torre-Amione G,Anker SD,Bourge RC,et al.Results of a non-specific immnomodulation therapy in chronic heart failure(ACCLAIM trial):a placebo-controlled randomized tral[J].Lancet,2008;371(9608):228-36.
2. Hunt SA,et al.ACC/AHA 2005 Chronic heart failure guideline update.J Am Coll Cardiol,2005:1116-43
3. Cleland JG,Khand A,Clark A.The heart failure epidemic:exactly how big is it?Eur Heart J.2001,22(8):623-6.
4.中国医学会心血管病学分会,中华心血管病杂志编辑委员会,2007中国慢性心力衰竭诊断治疗指南。中华心血管病杂志,2007,35(12).
5. Ho KK,Anderson KM,Kannel WB,et al.Survival after the onset of congestive heart failure in Framingham Heart Study subjects.Circulation,1993:88:107-15.
6. Greenberg BJ.Treatment of heart failure:states of the art and prospectives.Cardiovascus Pharmacol,2001,38:S59-S63.
7. Greenberg BJ.Treatment of heart failure:states of the art and prospectives.Cardiovascus Pharmacol,2001,38:S59-S63.
8. Hasegawa K,Iwaikanai E,Sasayama S.Neurohormonal regulation of myocardial cell apoptosis during the development of heart failure.J Cell Physiol,2001,186:11-18.
9. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.The SOLVD Investigation [J].N Engl J Med.1991,325:293-302.
10. The CONSENSUS Trial Study Group.Effects of enalapril on mortality in severe congestive heart failure.Results of the Cooperative NorthScandinavian Enalapril Survival Study(CONSENSUS)[J].N Engl J Med.1987,316:1249-1345
11. Cohn JN,Johnson G,Ziesche S,et al.A Comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic heart failure[J].N Engl J Med.1991,325:303-310
12. Waagstein F,Bristow MR,Swedberg K.et al.Beneficial effects of metaprolol in idiopathic in dilated cardiopmyopathy.The SPIC(Italian Multicentre Cardiomyopathy Study[J].Lancet,1993,342:141-1446.
13. Di Lenarda A,De Maria R,Gavazzi A,et al.Long-term survival effect of metaprolol in dilated cardiomyopathy. The SPIC(Italian Multicentre Cardiomyopathy Study) Group[J].Heart,1998,79:337-344.
14. The Cardiac Insufficiency Bisoprolol Study II(CIBIS-II):a randomized tril [J].Lancet,1999,353:9-13.
15. Packer M,Colucci US,Sackner-Bernstein JD,et al.Double-blind,placebo-controlled study of the effects of carvedilol in patients with moderate to sever heart failure.The PRICISE Trial Prospective randomized evaluation of carvedilol on symptoms and exercise[J].Circulation,1996,94:2793-2799.
16. Hunt SA,Abraham WT,Chin MH,et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society.Circulation,2005,112(12):e154-235.
17. Winlaw DS,Smythe GA,Keogh AM,et al.Nitric Oxide production and heart failure[J].Lancet,1993,341:390.
18. Ledoux J,Gee DM,Leblanc N.Increased peripheral resisitance in heart failure:new evdence suggests an alteration in vascular smooth muscle funtion[J].Bri J Pharmacol.2003,139:1245-1248.
19. Martin SR,Emanuel K,Sears CE,et al.Are myocardial eNOS and nNOS involved in the beta-adrenergic and muscarinic regulation of inotropy?A systematic investigation.Cardiovascular Research,2006,70(1):97-106.
20. Brown GC,Borvtaite V.Nitric oxide,cytochromec and mitochondria[J].Biochem Soc Symp,1999,66:17-25.
21. Rastaldo R,Pagliaro P,Cappello S,et al.Nitric Oxide and cardiac function.Life Sciences.2007,81:779-793.
22. Thomas SR,Chen K,Keaney JF.Oxidative stress and endothelial nitric oxide bioactivity[J].Antioxid Redox Signal,2003,5(2):181-194.
23. MacCarthy PY,Grocott-Mason R,Prendergast BD,et al.Contrasting inotropic effects of endogeneous endothelin in the normal and failing human heart[J].Circulation,2000,101:143-147.
24. Prendergast BD,Anning PB,Lewis MJ,et al.Regulation of left venricular relaxation in the isolate guinen-pig heart by endogenous endothelin.Cardiovasc Res.1997;33(1):131-8.
25. Spieker LE,Mitrovic V,Noll G,et al.Acute hemodynamic and neurohumoral effects of selective ETA-receptor blockade in patients with congestive heart failure[J].J Am Coll Cardiol,2000,35:1745-1752.
26. Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med, 2004; 351: 2049-57.
27. Murad S, Tajima SPinnell SR. A paradoxical effect of hydralazine on prolyland lysyl hydroxylase activities in cultured human skin fibroblasts. Arch Biochem Biophys, 1985; 241: 356-63.
28. Bruick RK, McKnight SL. A conserved family of prolyl-4-hydroxylases that modify HIF. Science, 2001; 294: 1337-40.
29. Epstein AC, Gleadle JM, McNeill LA, et al. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell, 2001; 107: 43-54.
30. Knowles HJ, Tian YM, Mole DR, et al. Novel mechanism of action for hydralazine: induction of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and angiogenesis by inhibition of prolyl hydroxylases. Circ Res, 2004; 95: 162-9.
31. Hayakawa H, Hirata Y, Kakoki M, et al. Role of nitric oxide-cGMP pathway in adrenomedullin-induced vasodilation in the rat. Hypertension, 1999; 33: 689-93.
32. Deramaudt BM, Braunstein S, Remy P, et al. Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis. J Cell Biochem, 1998; 68: 121-7.
33. Duckers HJ, Boehm M, True AL, et al. Heme oxygenase-1 protects against vascular constriction and proliferation. Nat Med, 2001; 7: 693-8.
34. Daiber A, Mulsch A, Hink U, et al. The oxidative stress concept of nitrate tolerance and the antioxidant properties of hydralazine. Am J Cardiol, 2005; 96: 25i-36i.
35. Munzel T,Kurz S,Rajagopdan S,et al.Hydralazine prevents nitroglycerin tolerance by inhibing activation of a membrane-bound NADH oxidase[J].J Clin Invest,1996,98:1465-1470
36. Bauer JA,Fung HL.Concurrent hydralazine administration preventsnitroglycerin-induced hemodynamic tolerance in experimental heart failure[J].Circulation,1991,84:35-39
37. Gogia h,Mehra A,Parikh S,et al.Prevention of tolerance to hemodynamic effects of nitrates with concomitant use of hydraiazine in patients with chronic heart failure[J].J Am Coll Cardiol,1995,26;1575-1580
38. Cohn JN,Archibald DG,Ziesche S,et al.Effect of vasodilator therapy on mortality in chronic congestive heart failure.Results of a Veterans Administeration Cooperative Study.N Engl J Med,1986,12;314(24):1547-52.
39. Rabelo E,De Angelis K,Bock P,et al.Baroreflex sensitivity and oxidative stress in adriamycin-induced heart failure.Hypertension.2001;38(3 Pt 2):576-80.
40. Hasenfuss G. Animal model of human cardiovascular disease,heart failure and hypertrophy[J ].Cardiovasc Res,1998,39 (1):60 - 76.
41. Weinberg EO,Schoen FJ,George D,et al. Angiotensin II convertingenzyme inhibition prolongs survival and modifies the transition to heart failure in rats with pressure overload hypertrophy due to ascending aortic stenosis [J ] . Circulation,1994,90(3) :1410– 1422.
42. Armal JF,Philippe M,Laboulandine I,et al.Effect of perindopril in rat cardiac volume overload[J ].Am Heart J,1993,126 (3):776- 782.
43. Underwood RD,Aarhus LL, Heublein DM,et al.Endothelin in thoracic inferior vena caval constriction model of heart failure[J ].Am J Physiol,1992 , 263 (3):H951 - H955.
44. Wilson JR,Douglas P,Hickey WF,et al.Experimental congestive heart failure produced by rapid ventricular pacing in the dog : Cardiac effects [J ].Circulation ,1987 , 75(4) :857– 867.
45. Smith HJ, Nuttall AA. Experimental models of heart failure [ J ] .CardiovascRes,1985,19(4):181 - 186.
46. Sharov VG,Sabbah HN,Shimoyama H,et al,Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure[J].AmJ Pathol ,1996,148(1):141 - 148.
47. Sabbah HN,Shimoyama H,Kono T,et al . Effects of longterm monotheraphy with enalapril,metoprolol and digoxin on the progression of left ventricular dysfunction and dilation in dogs withreduced ejection[J].Circulation,1994,89 (6) :2852-2859.
48. Arnolde L,Mcgrath B,Cocks M,et al.Adriamycin cardiomyopathyin the rabbit:An animal model of low output cardiac failure with activation of vasoconstrictor mechanisms[J].Cardiovasc Res,1985,191(67):378 - 382.
49. Singal PK,Iliskovic N.Doxorubicin induced cardiomyopathy[J].N Engl J Med,1998,339(13) :900- 905.
50. Wallace KB.Doxorubicin-induced cardiac mitochondrionopathy.Pharmacol Toxico1.2003,93(3):105-15.
51. Minotti G,Menna P,Salvatorelli E,et a1.Anthracyclines:molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity.Pharmacol Rev.2004,56(2):185-229.
52. Matsuhisa S,Otani H,Okazaki T,et al.N-acetylcysteine abolishes the protective effect of losartan against left ventricular remodeling in cardiomyopathy hamster.Antioxidants and Redox Signaling,2008,10(12):1998-2008.
53. Elliot JF,Liu Y,Yuan ZN,et al.Autoimmune cardiomyopathy and heart block develop spontaneously in HAL-DQ8 transgenic Iabeta knockout NOD mice.Proc Natl Acad Sci USA,2003,100(23):13447-13452.
54. Cohn JN.A-HeFT,old dog,new endothelial trial.Current Issues inCardiology,2005,32(2):366-368.
55. Cohn JN,Archibald DG,Ziesche S,et al.Effect of vasodilator therapy on mortality in chronic congestive heart failure.Results of a Veterans Administeration Cooperative Study.N Engl J Med,1986,12;314(24):1547-52.
56. Cohn JN,Johnson G,Ziesche S,et al.Comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of congestive heart failure.N Engl J Med,1991,325:303-310.
57. Nakanishi K, Zhao ZQ, Vinten-Johansen J, et al. Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction. J Thorac Cardiovasc Surg, 1995; 109: 1146-54.
58. Lewis NP, Tsao PS, Rickenbacher PR, et al. Induction of nitric oxide synthase in the human cardiac allograft is associated with contractile dysfunction of the left ventricle. Circulation, 1996; 93: 720-9.
59. Oddis CV,et al.Cytokine-Stimulated nitric oxide production inhibits mitochondrial activity in ardia myocytes.Biophys Res Commun,1995;213:1002.
60. Mohan P,et al.Myocardial contractile response to nitric oxide and cGMP.Circulation,1996;93:1223-9.
61. Matsuhisa S,Otani H,Okazaki T,et al.N-acetylcysteine abolishes the protective effect of losartan against left ventricular remodeling in cardiomyopathy hamster.Antioxidants and Redox Signaling,2008,10(12):1998-2008.
62. Cutler JA,Sorlie PD,Wolz M,et al.Trends in hypertension prevalence,awarness,treatment,and control rates in United States auldts between 1988 1994 and 1999 2004.Hypertension,2008;52;818-827.
63. Ferdinand KC.Fixed-dose isosorbide dinitrate-hydralazine:raced-based cardiovascular medicine benefit or mirage?J Law Med Enthics,2008;36(3):458-63.
64. Colvin-Adams M,Taylor AL.Isosorbide dinitrate-hydralazine improves outcomes in African Americans with heart failure.Cleve Clin J Med,2007;74(3):227-34.
65. Miyamoto Y,Saito Y,Kajiyama N,et al.Endothelial nitric oxide synthase gene is positively associated with essential hypertension[J].Hypertension,1998, 32:3 8.
66. Philip I,Plantefeve G,Vuillaumier-Barrot S,et al.G894T Polymorphism in the endothelial nitric oxide synthase gene is associated with an enhanced vascular responsiveness to phenylephrine [J].Circulation,1999,99:3096-3098.
67. McNamara DM,Tam SW,et al.Endothelial nitric oxide synthase(NOS3) polymorphisms in African Americans with heart failure:result from the A-HeFT trial.J card Fail.2009;15(3):191-8.
68.许丹,孙晓江.内皮源性一氧化氮合酶基因G894T多态性与脑梗死的关联性研究.中国老年学杂志2004年4月第24卷:340-343.
69. Yoshimuca M,Yasue H,Nakayama M,et al.A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in theJapanese.Hum Genet,1998,103:65-69.
70. The Beta-blocker Evaluation of Survival Trial Investigators.A trial of the beta-blocker buciondolol in patient with advanced chronic heart failure.N Engl J Med,2001,344:1659-1667.
71. Yancy CW,Flowler MB,Collucci WS,et al.Race and respose to a drenergic blockade with carvedilol in patients with chronic heart failure.N Engl J Med,2001,344:1358-1365.
72. Braunwald E.Expanding indications for beta-blockers in heart failure.N Engl J Med,2001,344:1711-1712.
73. Ferdinand KC.Fixed-dose isosorbide dinitrate-hydralazine:Race-based cardiovascular medicine benefit or mirage?J Law Med Ethics.2008,36(3):458-63.
74. Taylor AL,Ziesche S,Clyde W,et al.Early and sustained benefit on even-free survival and heart failure hospitalization from fixed-dose eombination of isosorbide dinitrate/hydralazine:consistency across subgroups in the African-American Heart Failure Trial.Circulation,2007;115;1747-1753.
75.中国医学会心血管病学分会,中华心血管病杂志编辑委员会,2007中国慢性心力衰竭诊断治疗指南。中华心血管病杂志,2007,35(12).
76. Dickstein K,Cohen-Solal A,Filippatos G,et al.ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008.European Heart Journal,2008,29:2388-2442.
77. American College of Cardiology,Foundation/American Heart Association Task,Force on Practice Guidelines International,Society for Heart and Lung Transplanation.2009 Focused Update:ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults.J Am Coll Cardiol,2009;53:1343-1382.
78. Martin SR,Emanuel K,Sears CE,et al.Are myocardial eNOS and nNOS involved in the beta-adrenergic and muscarinic regulation of inotropy?A systematic investigation.Cardiovascular Research,2006;70(1):97-106.
79. Damy T, Ratajczak P.Increased neuronal nitric oxide synthase-derived NO production in the failing human heart.The lancet.2004,363(9418):1365-1367
80. Hlubocka Z,Umnerova V,Heller S,et al.Circulating intercellular cell adhesion molecule-1,endothelin-1 and vonWillebrand factor 2 markers of endothelialdysfunction in uncomp licated essential hypertension:the effect of treatment with ACE inhibitors[J].J Hum Hypertens,2002,16 (8):557-562.
81. Sauzeau B,Rolli-Drekinderen M,Marionneau C,et al.RhoA expression is controlled by nitric oxide through cGMP-dependent protein kinase activation.J Biol Chem,2003,278(11);9472-80.
82. Kobayashi N,Higashi T,Hara K,et al.Effects of imidapril on NOS expression and myocardial remodeling in failure heart of Dahl salt-sensitive hypertensive rats.Cardiovasculr Research,1999,44:518-526.
83. Pasini AF,Garbin U,Stranieri C,et al.Nebivolol treatment reduces serum levels of asymmetric dimethylarginine and improves endothelial dysfunction in essential hypertensive patients.Am J Hypertens;2008;21(11):1251-7.
84. Dumont D,Pinaud F,Guihot AL,et al.Alteration in flow(shear stress)-induced remodeling in rat resisitance arteries with aging:improvement by a treatment with hydralazine.Cardiovasc Res,2008,77,600-608.
85. Sati Y,Kihara M,Hashimoto T,et al.Alterations in renal endothelial nitric oxide synthase exression by salt diet in angiotensin type-1a receptor gene knockout mice.J Am Soc Nephrol,2004;15:1756-1763.
86.张勇,夏勇,李东野.中国动脉硬化杂志,2006,14(5):391-394.
87. Horinaka S,Kobayashi N,Yagi H,et al.Nicorandil but not ISDN upregulates endothelial nitric synthase expression,preventing left ventricular remodeling and degradation of cardiac function in Dahl salt-sensitive hypertensive rats with congestive heart failure.J Cardiovasc Pharmacol.2006,47(5):629-35.
88. Jiang HB,Hirohito Y,Aizo F,et al.Effect of isosorbide dinitrate on nitric oxide synthase under hypoxia.Pharmacology,2001,62:10-16.
89. Matheis G,Sherman MP,Buckberg GP,et al.Role of L-arginine nitric oxide pathway in myocardial reoxygenation injury[J].Am JPhysiol,1992,262(2Pt2);H162-H620.
90. Jones SP,Greer JJ,van Haperen R,et al.Endothelial nitric oxide synthase overexpression attenuates congestive heart failure in mice.Proc Natl Acad Sci USA,2003,15:100(8):4891-6.
91. Heymes C,Vanderbeyden M,Jean GF,et al.Endomyocardial nitric synthase and left ventricular preload reserve in dilated cardiomyopathy[J].Circulation.1998,6:5009-8016.
92.向芙莉,冯清平.高血压杂志,2005,13(11):673-675.
93. Lewis NP, Tsao PS, Rickenbacher PR, et al. Induction of nitric oxide synthase in the human cardiac allograft is associated with contractile dysfunction of the left ventricle. Circulation, 1996,93: 720-9.
94.毛志芹,许玲芳,李军,等.血浆内皮素与降钙素基因相关肽在新生儿窒息中的动态变化及其临床意义[J].中国危重病急救医学,2002,14:696-697.
95.胡咏梅,李法琦,罗羽慧等.卡维地洛对压力负荷性大鼠心室重构及ET-1 mRNA表达的影响.高血压杂志,200412,03.
96. Smith RS Jr,Agata J,Xia CF,et al.Human endothelial nitric oxide synthase gene delivery protects against cardiac remodeling and reduces oxidative stress after myocardial infarction[J].Life Sci,2005,76(21):2457-2471.
97. Wang X,Ohnishi M,Wada A,et al.Endothelin-1 promotes vascular structural remodeling during the progression of heart failure prevention of vascular remodeling using a specific endothelin-converting enzyme inhibitor[J].Life Sci.2001,69(2):2477-2488.
98. Jugdutt BI,Idikio H,Uwiera RR.Therapeutic drugs during healing after myocardial infarction modify infarct collagens and ventricular distensibility at elevated pressures.Mol Cell Biochem,2007,304(1-2):79-91.
99. Amir O,Paz H,Rogowski O,et al.Serum oxidative stress level correlates withclinical parameters in chronic systolic heart failure patients[J].Clin Cardiol,2009,32(4):199-203.
100. Pu Q,Brassard P,Javeshghani DM,et al.Effects of combined AT1 receptor antagonist/NEP inhibitor on vascular remodeling and cardiac fibrosis in SHRSP.J Hypertensi,2008,26(2):322-33.
101. Quieles JL,Huertas JR,Battino M,et al.Antioxidant nutrents and adriamycin toxicity[J].Toxicology.2002,181(1):79-95.
102.李世红,王邵军.阿霉素心脏毒性发病机制新进展[J].临床心血管杂志,2005,21(4):249-250.
103.吴其夏,余应年,卢建.自由基损伤与疾病[J].病理生理学,2003:247-269.
104. Boucke RJ,Olson RD,Brener DE,et al.The major metabolite of doxorubicin is a potent inhibitor of membrane-associated in pumpa[J].J Biol Chem,1987,262:15815-15816.
105. Liang W,Tan CY,Ang L,et al.Ramipril improves oxidative stress-related vascular endothelial dysfunction in db/db mice[J].J Physiol Sci,2008,58(6):405-11.
106. Munzel T,Kurz S,Rajagopalan S,et al.Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase.A new acion for an old drug[J].J Clin Invest,1996,15,98(6)1465-70.
107. Forstermann U.Janus-faced role of endothelial NO skynthase in vascular disease:uncoupling of oxygen reduction from NO synthesis and its pharmacological reversal.Biol Chem.2006,387(12)1521-33.
108. Rugale C,Delbosc S,Mimran A,et al.Simvastatin reverses target organ damage and oxidative stress in Angiotensin II hypertension:comparison with apocynin,tempol,and hydralazine.J Cardiovasc Pharmacol.2007,50(3)293-8.
109. Reil TD,Moore WS,Kashyap VS.The effects ofthrombosis,thrombectomy and thrombolysis on endothelial function.Eur J Endovas Surg.2000,199(2):162-8.
1. Kannel WB,Ho K,Thom T.Changing epidemiological features of cardiac failure[J].Br Heart J,1994,723-9.
2.中国医学会心血管病学分会,中华心血管病杂志编辑委员会,2007中国慢性心力衰竭诊断治疗指南。中华心血管病杂志,2007,35(12).
3. Greenberg BJ.Treatment of heart failure:states of the art and prospectives.Cardiovascus Pharmacol,2001,38:S59-S63.
4. Van Zwieten PA.Changing insights in the drug treatment of congestive heart failure.Exp Opin Invest Drugs,1995,17:186-190.
5. Cosin J,Diez J,TORIC investigators.Torasemide in chronic heart failure:results of the TORIC study[J].Eur J Heart Fail,2002,4(4):507-513.
6. Chuen JM,MacFadyen RJ.Dose-dependent association between use of loop diuretics and mortality in advanced systolic heart failure[J].Am J Cardiol,2006,98(10):1416-1417.
7. Ferguson DW.Sympathctic mechanisms in heart failure.Pathophysiological and pharmacological implications.Circulation,1993,87(suppl VII):68-75.
8. Uretsky MF,Young JB,Eden Shahidi F,et al.Randomised study assessing the effect of digoxin withdrawl in patients with mild to moderate chronic congestive heart failure;results of the PROVED Trial.J Am Coll Cardiol,1993,22,955-962.
9. Packer M,Geoghiade M,Young JB,et al.Withdrawl of digoxin from patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors.N Engl J Med,1993,329:1-7.
10. Cohn JN,Archibald DG,Ziesche S,et al.Effect of vasodilator therapy onmortality in chronic congestive heart failure.Results of a Veterans Administeration Cooperative Study.N Engl J Med,1986,12;314(24):1547-52.
11. Cohn JN,Johnson G,Ziesche S,et al.A Comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic heart failure[J].N Engl J Med.1991,325:303-310.
12. Cohn JN,Ziesche SM,Loss LE,et al.Effect of felodipine on short-term mortality in heart failure.Results of V-HeFT III.Circulation,1995,92;1-143.
13. O’Connor CM,Belkin RN,Carson PE,et al.For the PRAISE Investigators.Effect of amlodipine on mode of death in severe heart failure:The PRAISE Trial.Circulation,1995,92(suppl I):1-143.
14. Echols MR,Yancy CW.Isosorbide dinitrate-hydralazine combination therapy in African Americans with heart failure.Vascular Health and Risk Management,2006:2(4):423-431.
15. Winlaw DS,Smythe GA,Keogh AM,et al.Nitric Oxide production and heart failure[J].Lancet,1993,341:390.
16. Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med, 2004; 351: 2049-57.
17. Dickstein K,Cohen-Solal A,Filippatos G,et al.ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008:the Task Force for the diagnosis and treatment of acute and Chronic heart failure 2008 of the European Society of Cardiology Developed in Collaboration with the Heart Failure Association of the ESC(HFA) and endorsed by the European Society of Intensive Care Medicine(ESICM).Eur J Heart Fail.2008;10(10):933-89.
18. American College of Cardiology,Foundation/American Heart Association Task,Force on Practice Guidelines International,Society for Heart and LungTransplanation.2009 Focused Update:ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults.J Am Coll Cardiol,2009;53:1343-1382.
19. Paul JR,Widdop RE.Persisitent cardiovascular effect of chronic rein-angiotensin system inhibition following withdraw in adult spontaneously hypertensive rats.J Hypertens,2001,19:1393-1402.
20. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.The SOLVD Investigation [J].N Engl J Med.1991,325:293-302.
21. Cohn JN,Johnson G,Ziesche S,et al.A Comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic heart failure[J].N Engl J Med.1991,325:303-310
22. The CONSENSUS Trial Study Group.Effects of enalapril on mortality in severe congestive heart failure.Results of the Cooperative North Scandinavian Enalapril Survival Study(CONSENSUS)[J].N Engl J Med.1987,316:1249-1345.
23.中国医学会心血管病学分会,中华心血管病杂志编辑委员会,2007中国慢性心力衰竭诊断治疗指南。中华心血管病杂志,2007,35(12).
24. Pitt B,Poole-Wilson PA,Segal R,et al.Effect of losartan compared with captopril on mortality in patients with syptomatic heart failure:randomised trial-the Losartan Heart Failure Survival Study ELITE II.Lancet,2000,355(9215):1582-1587.
25. Granger CB,McMurray JJ,Yusuf S,et al.Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors:the CHARM-Alternative trial.Lancet,2003,362(9386):772-776.
26. Wong M,Staszewsky L,Latini R,et al.Valsartan benefits left ventricular structure and function in heart failure:Val-HeFT echocardiographic study.J Am Coll Cardiol,2002,40(5):970-975.
27. Lijnen P,Petrov V.Induction of cardiac fibrosis by aldosterone[J].Mol Cell Cardiol,2003,32(6):865-879.
28. Pitt B,Zannad F,Remme WJ,et al.The effect of spironolactone on morbidity and mortality in patients with severe heart failure.Randomized Aldosterone Evaluation Study Investigators.N Engl J Med,1999;341(10):709-17
29. Juurlink DN,Mamdani MM,Lee DS,et al.Rates of hyperkalemia after publication of the Randomized Aldosterone Evaluation Study.N Engl J Med.2004,351(6):543-51.
30. Wang D,Liu YH,Yang XP,et al.Role of a selective aldosterone blocker in mice with chronic heart failure[J].Card Fail,2004,10(1):67-73.
31. Pitt B,Remme W,Zannad F,et al.Eplernone,a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.N Engl J Med.2003,348(14):1309-21.
32. The Cardiac Insufficiency Bisoprolol Study II(CIBIS-II):a randomised trial.Lancet,1999;353(9146):9-13.
33. Hjalmarson A,Goldstein S,Fagerberg B,et al.Effects of controlled-release metroprolol on tota mortality,hospitalizations,and well-being in patients with heart failure.the Metoprlol CR/XL Randomized Intervention Trial in congestive heart failure(MERIT-HF).JAMA,2000;283:1295-1302.
34. Dargie HJ.Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction:the CAPRICONN randomised trial.Lancet.2001;357:1385-1390.
35. Cleland JG,Pennell DJ,Ray SG,et al.Myocardial viability as a determinant ofejection fraction response to carvedilol in patients with heart failure(CHRISTMAS trial):randomised controlled trial.Lancet,2003:362:4-21.
36. Flather MD,Shibatta MC,Coats AJ,et al.Randomized trial to determine the effect of nebivolol on mortality and cardovascular hospital admission in elderly patients with heart failure(SENIORS).Eur Heart J,2005;26:215-225.
37. Winlaw DS,Smythe GA,Keogh AM,et al.Nitric Oxide production and heart failure[J].Lancet,1993,341:390.
38. Mulder P,Boujedanini H,Richard V,et al.Selective endothelin-A versum combined endothelin-A/endothelin-B receptor blockeade in rat chronic heart failure[J].Circulation,2000,102(5):491-493.
39. Nakanishi K, Zhao ZQ, Vinten-Johansen J, et al. Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction. J Thorac Cardiovasc Surg, 1995; 109: 1146-54.
40. Ruiz-Hurtado G,Fernandez-Velasco M,Mourelle M,et al.LA419,a novel nitric oxide donor,prevent pathological cardiac remodeling in pressure-overloaded rats via endothelial nitric oxide synthase pathway regulation.Hypertension,2007;50(6):1049-56.
41. Go AS,Lee WY,Yang J,et al.Statins therapy and risks for death and hospitalization in chronic heart.JAMA,2006;296(17):2105-11.
42.赵水平.他汀类药物在慢性心力衰竭防治中的研究现状[J].中华老年心脑血管病杂志,2004,6,6:289-291.
43. Kjekshus J,Apetrei E,Barrios V,et al.Rosuvastatin in older patients with systolic heart failure.N Engl J Med,2007;357(22):2246-61.
44. Gissi-HF Investigators.Effect of rosuvastatin in patients with chronicfailure(the GISSI-HF trial):a randomised,double-blind,placebo-controlled trial.Lancet.2008;372(9645):1231-9.
45. Fenster BE,Tsao S,Rockson SG,et al.Endothelial dysfunction:Clinical strategies for treating oxidant stress[J].Am Heart J,2003,146(2):216-226.
46. Yancy CW.Treatment with B-type natriuretic peptide for chronic decopensated heart failure:insights learned from the follow-up serial infusion of nesiritide(FUSION)trial[J].Heart Fail Rev,2004,9 (3):209-16.
47. Kyrzopoulos S,Adamopoulos S,Parissis JT,et al.Levosimendan reduces plasma B-type natriuretic peptide and interleukin 6,and improves central hemodynamics in severe heart failure patients.Int J Cardiol.2005;99(3):409-13.
48. Abraham WT.Rationale and design of a randomized clinical trial to assess the safty and efficacy of cardiac resynchronization therapy in patients with advanced heart failure:the Multicenter InSync Randomized Clinical Evaluation(MIRACLE)[J].J Card Fail,2000,6(4):369-380.
49. Bristow MR,Saxon LA,Boehmer J,et al.The comparison of Medical Therapy,Pacing and Defibrillation in Heart Failure(COMPANION)Investigators.Cardiac-Resynchronization Therapy with or without an Implantable Defibrillation in Adbanced Chronic Heart Failure[J].N Engl J Med,2004,350:2140-2150.
50. Mark DB,Nelson CL,Anstron KJ,et al.Cost-effectiveness of defribrillator therapy or amiodarone in chronic stable heart failure:results from the Sudden Cardiac Death in Heart Failure Trial(SCD-HeFT)[J].Circulation,2001,114(2):135-142.
51. Young JB,Abraham WT,Smith AL,et al.Combined cardiac resynchronization and implantable cardio version defibrillator in advanced chronic heartfailure:the MIRACLE ICD trial[J].JAMA,2003,289:2685-2694.
52. Graf T.Differntiation plasticity of hematopoietic cells[J].Blood,2002,99:3089-3101.
53. Schaefer A,meyer GP,Fuchs M,et al.Impact of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction:results from the BOOTS trial[J].Eur Heart J,2006,27(8):929-935.
54. Anker SD,von Heahling S.Inflammatory mediators in chronic heart failure:an over-view[J].Heart,2004;90:464
55. Gullestad L,Aukrust P.Review of trials in chronic heart failure showing broad-spectrum anti-inflammatory approaches[J].Am J Cardiol,2005,95(suppl):17C.
56. Chung ES,Packer M,Lo KH,et al.Randomized,double-blind,placebo-cntrolled,pilot trial of infliximab,a chimeric monoclonal antibody to tumor necrosis factor-alpha,in patients with moderate-to-severe heart failure:results of anti-TNF Therapy Against Congestive Heart Failure(ATTACH)trial[J].Circulation,2003,107(25):3133.
57. Mann DL,McMurry JJ,Packer M,et al.Targeted anticytokine therapy in patients with chronic heart failure:results of the Randomized Etanercept Worldwide Evaluation(RENEWAL)[J].Circulation,2004,109(13):1594.
58. Torre-Amione G,Sestier F,Radovancevic B,et al.Effects of a novel immune modulation therapy in patients with advanced chronic heart failure:results of a randomized,controlled phaseⅡtrial[J].J Am Coll Cardiol.2004,44(6):1181-6.
59. Torre-Amione G,Anker SD,Bourge RC,et al.Results of a non-specific immnomodulation therapy in chronic heart failure(ACCLAIM trial):a placebo-controlled randomized tral[J].Lancet,2008;371(9608):228-36.