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Future Pharmacologic Agents for Treatment of Heart Failure in Children

Pediatric Cardiology volume 27, pages 533–551 (2006)Cite this article

Abstract

The addition of new agents to the armamentarium of treatment options for heart failure in pediatric patients is exciting and challenging. Administration of these therapies to pediatric patients will require careful scrutiny of the data and skilled application. Developmental changes in drug metabolism, excretion, and distribution are concerning in pediatric patients, and inappropriate evaluation of these parameters can have disastrous results. Manipulation of the neurohormonal pathways in heart failure has been the target of most recently developed pharmacologic agents. Angiotensin receptor blockers (ARBs), aldosterone antagonists, beta-blockers, and natriuretic peptides are seeing increased use in pediatrics. In particular, calcium sensitizing agents represent a new frontier in the treatment of acute decompensated heart failure and may replace traditional inotropic therapies. Endothelin receptor antagonists have shown benefit in the treatment of pulmonary hypertension, but their use in heart failure is still debatable. Vasopressin antagonists, tumor necrosis factor inhibitors, and neutral endopeptidase inhibitors are also targeting aspects of the neurohormonal cascade that are currently not completely understood. The future of pharmacologic therapies will include pharmacogenomic studies on new and preexisting therapies for pediatric heart failure. The education and skill of the practitioner when applying these agents in pediatric heart failure is of utmost importance.

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References

  1. Anker SD, Coats AJ (2002) How to RECOVER from RENAISSANCE? The significance of the results of RECOVER, RENAISSANCE, RENEWAL and ATTACH. Int J Cardiol 86:123–130

    PubMed  Google Scholar 

  2. Antila S, Asko J, Honkanen T, Letonen L (2000) Pharmacokinetic and pharmacodynamic interactions between the novel calcium sensitizer levosimendan and warfarin. Eur J Clin Pharmacol 56:705–710

    Google Scholar 

  3. Antila S, Eha J, Heinpalu M, et al. (1996) Haemodynamic interactions of a new calcium sensitizing drug levosimendan and captopril. Eur J Clin Pharmacol 49:451–458

    PubMed  CAS  Google Scholar 

  4. Antila S, Honkanen T, Lehtonen L, Neuvonen PJ (1998) The CYP3A4 inhibitor intraconazole does not affect the pharmacokinetics of a new calcium sensitizing drug levosimendan. Int J Clin Pharmacol Ther 36:446–449

    PubMed  CAS  Google Scholar 

  5. Antila S, Huuskohen H, Nevalainen T, et al. (1999) Site dependent bioavailability and metabolism of levosimendan in dogs. Eur J Pharm Sci 9:85–91

    PubMed  CAS  Google Scholar 

  6. Antila S, Jarvinen A, Akkila J, et al. (1997) Studies on psychomotoric effects and pharmacokinetic drug interactions of the new calcium sensitizing drug levosimendan and ethanol. Arnzneimittelforschung 47:816–820

    CAS  Google Scholar 

  7. Azeka E, Ramires JAF, Valler C, Bocchi EA (2002) Delisting of infants and children from the heart transplantation waiting list after carvedilol treatment. J Am Coll Cardiol 40:2034–2038

    PubMed  CAS  Google Scholar 

  8. Berger R, Stanek B, Hulsmann M, et al. (2001) Effects of endothelin A receptor blockade on endothelin function in patients with chronic heart failure. Circulation 103:981–986

    PubMed  CAS  Google Scholar 

  9. Boekstegers P, Wedenhofer S, Zell R, et al. (1994) Repeated administration of a F(ab’)2 fragment of an anti-tumor necrosis factor alpha monoclonal antibody in patients with severe sepsis: effects on the cardiovascular system and cytokine levels. Shock 1:237–245

    PubMed  CAS  Google Scholar 

  10. Book WM, Hott BJ, McConnell M (2005) B-type natriuretic peptide levels in adults with congenital heart disease and right ventricular failure. Am J Cardiol 95:545–546

    PubMed  CAS  Google Scholar 

  11. Bosentan package insert (2003) Actelion Pharmaceuticals US South San Francisco,CA

  12. Bozkurt B, Torre-Amione G, Warren M, et al. (2001) Results of targeted anti-tumor necrosis factor therapy with Etanercept (ENBREL) in patients with advanced heart failure. Circulation 103:l044–1047

    Google Scholar 

  13. Braun JP, Schneider M, Dohmen P, Dopfmer U (2004) Succesful treatment of dilative cardiomyopathy in a 12-year-old girl using the calcium sensitizer levosimendan after weaning from mechanical biventricular assist support. J Cardiothorac Vasc Anesth 18:772–774

    PubMed  Google Scholar 

  14. Braur JP, Schneider M, Kastrup M, Liu J (2004) Treatment of acute heart failure in an infant after cardiac surgery using levosimendan. Eur J Cardiothorac Surg 26:228–230

    Google Scholar 

  15. Brehm BR, Wolf SC, Bertsch D, et al. (2001) Effects of nebivolol on proliferation and apsoptosis on human coronary artery smooth muscle and endothelial cells. Cardiovasc Res 49:430–439

    PubMed  CAS  Google Scholar 

  16. Brehm BR, Wolf SC, Corner S, et al. (2002) Effect of nebivolol on left ventricular function in patients with chronic heart failure: a pilot study. Eur J Heart Fail 4:757–763

    PubMed  CAS  Google Scholar 

  17. Brickner ME, Hillis LD, Lange RA (2000) Congenital heart disease in adults. N Engl J Med 342:252–263

    Google Scholar 

  18. Bristow MR (1997) Mechanism of action of beta-blocking agents in heart failure. Am J Cardiol 80:26L–40L

    PubMed  CAS  Google Scholar 

  19. Brouard R, Laporte V, Serradeil-Le Gal C, et al. (1998) Safety, tolerability, and pharmacokinetics of SR 49059, a VI a vasopressin receptor antagonist, after repeated oral administration in healthy volunteers. Adv Exp Med Biol 449:455–465

    PubMed  CAS  Google Scholar 

  20. Bruns LA, Chrisant MK, Lamour JM, et al. (2001) Carvedilol as therapy in pediatric heart failure: an initial multicenter experience. J Pediatr 138:505–511

    PubMed  CAS  Google Scholar 

  21. Burger AJ, Elkayam U, Neibaur M, et al. (2001) Comparison of the occurrence of ventricular arrhythmias in patients with acutely decompensated congestive heart failure receiving dobutamine vs. nesiritide therapy. Am J Cardiol 88:35–39

    PubMed  CAS  Google Scholar 

  22. Burnier M (2000) Angiotensin II type I receptor blockers. Circulation 103:904–912

    Google Scholar 

  23. Burnier M, Fricker AF, Hayoz D, et al. (1999) Pharmacokinetic and pharmacodynamic effects of YM087, a combined V1/V2 vasopressin receptor antagonist in normal subjects. Eur J Clin Pharmacol 55:633–637

    PubMed  CAS  Google Scholar 

  24. Campbell H, Surry SAM, Royle EM (1998) A review of randomized controlled trial published in the Archives of Disease in Childhood from 1982–96. Arch Dis Child 79:192–197

    PubMed  CAS  Article  Google Scholar 

  25. Carson P, Ziesche S, Johnson G, et al. (1999) Racial differences in response to therapy for heart failure: analysis of the vasodilator heart failure trials. Vasodilator-Heart Failure Trial Study Group. J Card Fail 5:178–187

    PubMed  CAS  Google Scholar 

  26. Cascorbil, Gerloff T, Johne A, et al. (2001) Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther 69:169–174

    Google Scholar 

  27. Colucci WS, Elkayam U, Horton DP (2000) Intravenous nesritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide study group. N Engl J Med 343:246–253

    PubMed  CAS  Google Scholar 

  28. Costello-Boerrigter LC, Smith WB, Boerrigter G, et al. (2006) Vasopressin-2 receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure. Am J Physiol Renal Physiol 290(2):F273–F278

    PubMed  CAS  Google Scholar 

  29. Cotter G, Kaluski E, Stangl K, et al. (2004) The hemodynamic and neurohormonal effects of low doses of tezosentan (an endothelin A/B receptor antagonist) in patients with acute heart failure. Eur J Heart Fail 6:601–609

    PubMed  CAS  Google Scholar 

  30. Crozier I, Ikram H, Awan N, et al. (1995) Losartan in heart failure: hemodynamic effects and tolerability. Circulation 91:691–697

    PubMed  CAS  Google Scholar 

  31. Danser AH, Schalekamp MA, Bax WA, et al. (1995) Angiotensin converting enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation 92: 1387–1388

    PubMed  CAS  Google Scholar 

  32. Data on file. Bosentan use in pediatrics. Actelion Pharmaceuticals, South San Francisco, CA

  33. Data on file. Use in pediatrics. Pfizer Pharmaceuticals Group, Kalamazoo, MI

  34. de Gasparo M, Levens N (1988) Does blockade of angiotensin II receptors offer clinical benefits over inhibition of angiotensin-converting enzyme? Pharmacol Toxicol 82:257–271

    Article  Google Scholar 

  35. Delyani JA, Myles K, Funder J (1998) Eplerenone (SC 66110), a highly selective aldosterone antagonist [Abstract]. Am J Hypertens 11:94A

    Google Scholar 

  36. Delyani JA, Robinson EL, Rudolph AE (2001) Effect of a selective aldosterone receptor antagonist in myocardial infarction. Am J Physiol Heart Circ Physiol 281:H647–H654

    PubMed  CAS  Google Scholar 

  37. Delyani JA, Rocha R, Cook CS, et al. (2001) Eplerenone: a selective aldosterone receptor antagonist (SARA). Cardiovasc Drug Rev 19:185–200

    PubMed  CAS  Article  Google Scholar 

  38. Deswal A, Bozkurt B, Seta Y, et al. (1999) Safety and efficacy of a soluble P75 tumor necrosis factor receptor (Enbrel, Entanercept) in patients with advanced heart failure. Circulation 99:3224–3226

    PubMed  CAS  Google Scholar 

  39. Dieaguez-Lucena JL, Aranda-Lara P, Ruiz-Galdoh M, et al. (1996) Angiotensin I-converting enzyme genotypes and angiotensin II receptors. Response to therapy. Hypertension 28:98–103

    Google Scholar 

  40. Edes I, Gasior Z, Wita K (2005) Effects of nebivolol on left ventricular function in elderly patients with chronic heart failure: results of the ENECA study. Eur J Heart Fail 7:631–639

    PubMed  CAS  Google Scholar 

  41. Edes I, Kiss E, Kitada Y et al. (1995) Effects of levosimendan, a cardiotonic agent targeted to troponin C, on cardiac function and on phosphorylation and Ca2+ sensitivity of cardiac myofibrils and sarcoplasmic reticulum in guinea pig heart. Circ Res 77:107–131

    PubMed  CAS  Google Scholar 

  42. Edwards BS, Zimmerman RS, Schwab TR, et al. (1988) Atrial stretch, not pressure, is the prinicipal determinant controlling the release of atrial natriuretic factor. Circ Res 62:191–195

    PubMed  CAS  Google Scholar 

  43. Ellis D, Moritz ML, Vats A, Janosky JE (2004) Antihypertensive and renoprotective efficacy and safety of losartan. A long-term study in children with renal disorders. Am J Hypertens 17:928–935

    PubMed  CAS  Google Scholar 

  44. Eplerenone Package insert (2003) Pfizer Pharmaceuticals Group, Kalamazoo, MI

  45. Etanercept (Enbrel). Data on File. Amgen Corporation, Seattle, WA

  46. Etanercept (Enbrel) (2002) Package insert. Amgen Corporation, Seattle, WA

  47. Exner DV, Dries DL, Domanski MJ, et al. (2001) Lesser response to angiotensin-converting enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. N Engl J Med 344:1351–1357

    PubMed  CAS  Google Scholar 

  48. Feingold B, Law YM (2004) Use of nesiritide in pediatric patients with congestive heart failure. J Heart Lung Transplant 23:1455–1459

    PubMed  Google Scholar 

  49. Feldman AM, McTiernan C (2004) Is there any future for tumor necrosis factor antagonists in chronic heart failure? Am J Cardiovasc Drugs 4:11–19

    PubMed  CAS  Google Scholar 

  50. Fichtischerer S, Rossig L, Breuer S, et al. (2001) Tumor necrosis factor antagonism with Etanercept improves systemic endothelial vasoreactivity in patients with advanced heart failure. Circulation 104:3023–3025

    Google Scholar 

  51. Flather MD, Shibata MC, Coat AJ, et al. (2005) SENIORS Investigators. Randomized trial to determine the effect of nebivolol an mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 26:215–252

    PubMed  CAS  Google Scholar 

  52. Follath F, Cleland JGF, Just H, et al. (2002) Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LiDO study): a randomized double-blind trial. Lancet 360:196–202

    PubMed  CAS  Google Scholar 

  53. Follath F, Franco F, Cardoso JS (2005) European experience on the practical use of levosimendan in patients with acute heart failure syndromes. Am J Cardiol 96:80G–85G

    PubMed  CAS  Google Scholar 

  54. Francis GS (1999) Is there still a future neutral endopeptidase inhibitors? Am Heart J 138:1007–1008

    PubMed  CAS  Google Scholar 

  55. Garban HJ, Buga GM, Ignarro LJ (2004) Estrogen receptor-mediated vascular responsiveness to nebivolol: a novel endothelium-related mechanim of therapeutic vasorelaxation. J Cardiovasc Pharmacol 439:638–644

    Google Scholar 

  56. Gheorghiade M, Niazi I, Ouyang J (2003) Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation 107:2690–2696

    PubMed  CAS  Google Scholar 

  57. Gheorghiade M, Orlandi C, Burnett JC, et al. (2005) Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of vasopressin antagonism heart failure: outcome study with tolvaptan (EVEREST). J Card Fail 11:260–269

    PubMed  CAS  Google Scholar 

  58. Giardini A, Formigari R, Bronzetti G, et al. (2003) Modulation of neurohormonal activity after treatment of children in heart failure with carvedilol. Cardiol Young 13:333–336

    PubMed  Google Scholar 

  59. Givertz MM, Colucci WS, LeJemtel TH, et al. (2000) Acute endothelin a receptor blockade causes selective pulmonary vasodilation in patients with chronic heart failure. Circulation 101:2922–2927

    PubMed  CAS  Google Scholar 

  60. Goldsmith SR, Francis GS, Cowley AW Jr (1986) Arginine vasopressin and the renal response to water loading in congestive heart failure. Am J Cardiol 58:295–299

    Google Scholar 

  61. Granger CB, McMurray JJ, Yusuf S, et al. (2003) CHARM Investigators and Committees. Effects of candesartan patients with chronic heart failure and preserved left-ventricularjejection fraction: the CHARM-Preserved Trial. Lancet 362:777–781

    PubMed  Google Scholar 

  62. Haikala H, Linden I-B (1995) Mechanisms of action of calcium-sensitizing drugs. J Cardiovasc Pharmacol 26(Suppl 1): S10–S19

    PubMed  CAS  Google Scholar 

  63. Harjola V, Peuhkurinen K, Nieminen M, et al. (1999) Oral levosimendan improves cardiac function and hemodynamics in patients with severe congestive heart failure. Am J Cardiol 83:4(l)–8(l)

    Google Scholar 

  64. Heinemann A, Horina G, Stauber RE, et al. (1998) Lack of effect of a selective vasopressin V1a receptor anatagonist SR 49059, on potentiation by vasopressin of adrenoceptor-mediated pressor responses in the rat mesenteric arterial bed. Br J Pharmacol 125:1120–1127

    CAS  Google Scholar 

  65. Hoch M, Netz H (2005) Heart failure in pediatric patients. Thorac Cardiovasc Surg 53(Suppl 2):S129–S134

    PubMed  Google Scholar 

  66. Horenstein MS, Ross RD, Singh TP, Epstein ML (2002) Carvedilol reverses elevated pulmonary vascular resistance in a child with dilated cardiomyopathy. Pediatr Cardiol 23:100–102

    PubMed  CAS  Google Scholar 

  67. Horiuchi M, Nishiyana H, Hama J, et al. (1993) Characterization of renal aldosterone receptors in genetically hypertensive rats. Am J Physiol 264:F286–F291

    PubMed  CAS  Google Scholar 

  68. Hosenpud J, Levosimendan, (1999) a novel myofilament calcium sensitizer, allows weaning of parenteral inotropic therapy in patients with severe congestive heart failure. Am J Cardiol 83:9(l)–11(l)

    Google Scholar 

  69. Infliximab (Remicade) Package insert (2003) Centocor, Malvern, PA

  70. Intravenous nesiritide vs. nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial (2002) J Am Med Assoc 287:1531–1540

    Google Scholar 

  71. Itoh H, Pratt RE, Dzau VJ (1990) Atrial natriuretic polypeptide inhibits hypertrophy of vascular smooth muscle cells. J Clin Invest 86:1690–1697

    PubMed  CAS  Google Scholar 

  72. Jain KK (2004) Role of pharmacoproteomics in the development of personalized medicine. Pharmacogenomics 5:331–336

    PubMed  CAS  Google Scholar 

  73. Janssen PM, Zeitz O, Hasenfuss G (1999) Transient and sustained impacts of hydroxy radicals on sarcoplasmic reticulum function: the protective effects of nebivolol. Eur J Pharmacol 366:223–232

    PubMed  CAS  Google Scholar 

  74. Jong P, Demers C, McKelvie RS, Liu PP (2002) Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials. J Am Coll Cardiol 39:463–470

    PubMed  CAS  Google Scholar 

  75. Kahn JC, Patey M, Dubois-Rande JL, et al. (1990) Effect of sinorphan on plasma atrial natriuretic factor in congestive heart failure. Lancet 335:118–119

    PubMed  CAS  Google Scholar 

  76. Kaluski E, Kobrin I, Zimlichman R, et al. (2003) RITZ-5: randomized intravenous tezosentan (an endothelin A/B antagonist) for the treatmert of pulmonary edema. J Am Coll Cardiol 41:204–210

    PubMed  CAS  Google Scholar 

  77. Kaye DM, Lefkovits J, Jennings GL, et al. (1995) Adverse consequences of high sympathetic nervous activity in the failing heart. J Am Coll Cardiol 26:1257–1263

    PubMed  CAS  Google Scholar 

  78. Kearns GL (1995) Pharmacogenetics and development: are infants and increased risk for adverse outcomes? Curr Opin Pediatr 7:220–233

    PubMed  CAS  Google Scholar 

  79. Kearns GL (2000) Impact of developmental pharmacology on pediatric study design: overcoming the challenges. J Allergy Clin Immunol 106:S128–S138

    PubMed  CAS  Google Scholar 

  80. Kim S, Ohta K, Hamaguchi A, et al. (1995) Angiotensin II type 1 receptor antagonist inhibits gene expression of transforming growth factor-ß1 and extracellular matrix in cardiac and vascular tissue of hypertensive rats. J Pharmacol Exp Ther 273:509–551

    PubMed  CAS  Google Scholar 

  81. Kiowski W, Sutsch G, Hunziker P, et al. (1995) Evidence for endothelin-l-mediated vasoconstriction in severe chronic heart failure. Lancet 246:732–736

    Google Scholar 

  82. Kivikko M, Antila S, Eha J, et al. (2002) Pharmacodynamics and safety of a new calcium sensitizer, levosimendan, and its metabolites during an extended infusion in patients with severe heart failure. J Clin Pharmacol 42:43–51

    PubMed  CAS  Google Scholar 

  83. Kivikko M, Antila S,Eha J, et al. (2003) Pharmacokinetics of levosimendan and its metabolites during and after a 24-hour continuous infusion in patients with severe heart failure. Int J Clin Pharmacol Ther 40:465–471

    Google Scholar 

  84. Kivikko M, Lehtonen L, Colucci W, et al. (2003) Sustained hemodynamic effects of intravenous levosimendan. Circulation 107:81–86

    PubMed  CAS  Google Scholar 

  85. Kleerekoper Q, Putkey JA (1999) Drug binding to cardiac troponin C. J Biol Chem 274:23932–23939

    PubMed  CAS  Google Scholar 

  86. Koller KJ, Goeddel DV (1992) Molecular biology of the natriuretic peptides and their receptors. Circulation 86:1081–1088

    PubMed  CAS  Google Scholar 

  87. Kopustinskiene D, Pollesello P, Saris N (2001) Levosimendan is a mitochondrial KATP channel opener. Eur J Pharmacol 428:311–314

    PubMed  CAS  Google Scholar 

  88. Kopustinskiene DM, Pollesello P, Saris NE (2004) Potassium-specific effecrs of levosimendan on heart mitochondria. Biochem Pharmacol 68:807–821

    PubMed  CAS  Google Scholar 

  89. Kostrzewska A, Laudanski T, Steinwall M, et al. (1998) Effects of the vasopressin V1a receptor antagonist, SR 49059, on the response of human uterine arteries to vasopressin and other vasoactive substances. Acta Obstet Gynecol Scand 77:3–7

    PubMed  CAS  Google Scholar 

  90. Laer S, Mir TS, Behn F, Eiselt M, et al. (1998) Carvedilol therapy in pediatric patients with congestive heari failure: a study investigating clinical and pharmacokinetic parameters. Am Heart J 143:916–922

    Google Scholar 

  91. Law YM, Keller BB, Feingold BM, Boyle GJ (2005) Usefulness of plasma B-type natriuretic peptide to identify ventricular dysfunction in pediatric and adult patients with congenital heart disease. Am J Cardiol 95:474–478

    PubMed  CAS  Google Scholar 

  92. Leeder JS, Kearns GL (1997) Pharmacogenetics in pediatrics. Implications for practice. Pediatr Clin North Am 44:55–77

    PubMed  CAS  Google Scholar 

  93. Lehtonen LA, Antila S, Pentikainen PJ (2004) Pharmacokinetics and pharmacodynamics of intravenous inotropic agents. Clin Pharmacokinet 43:187–203

    PubMed  CAS  Google Scholar 

  94. Lepran I, Papp J (2003) Effect of long-term oral pretreatment with levosimendan on cardiac arrhythmias during coronary artery occlusion in conscious rats. Eur J Pharmacol 464:171–176

    PubMed  CAS  Google Scholar 

  95. Levijoki J, Piero P, Kaivola J, et al. (2000) Further evidence for the cardiac troponin C mediated calcium sensitization by levosimedan: structure–response and binding analysis with analogs of levosimendan. J Mol Cell Cardiol 32:479–491

    PubMed  CAS  Google Scholar 

  96. Levine B, Kalman H, Mayer L, et al. (1990) Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Eng J Med 323:236–241

    CAS  Article  Google Scholar 

  97. Lilleberg J, Antila S, Karlsson M, et al. (1994) Pharmacokinetics and pharmacodynamics of simendan, a novel calcium sensitizer, in healthy volunteers. Clin Pharmacol Ther 56:554–563

    PubMed  CAS  Article  Google Scholar 

  98. Lilleberg J, Nieminen S, Akkila J, et al. (1998) Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting. Eur Heart J 19:660–668

    PubMed  CAS  Google Scholar 

  99. Liu JJ, Chen JR, Buxton BB, et al. (1995) Potent inhibitory effect of SR 49059, an orally active non-peptide vasopressin Via receptor antagonist, on human arterial coronary bypass graft. Clin Sci (Londn) 89:481–485

    CAS  Google Scholar 

  100. Loichot C, Cazaubon C, De Jong W, et al. (2000) Nitric oxide, but not vasopressin V2 receptor-mediated vasodilation, modulates vasopressin-induced renal vasoconstriction in rats. Naunyn Schmeidebergs Arch Pharmacol 361:319–326

    Google Scholar 

  101. Luscher TF, Enseleit F, Pacher R, et al. (2002) Hemodynamic and neurohormonal effects of selective endothelin A (ET A ) receptor blockade in chronic heart failure. Circulation 106:2666–2672

    PubMed  Google Scholar 

  102. Luther YC, Schulze-Neick I, Stiller B, et al. (2004) Levosimendan–long-term inodilation in an infant with myocardial infarction. Z Kardiol 93:234–239

    PubMed  CAS  Google Scholar 

  103. Maggioni AP, Anand I, Gottlieb SO, et al. Val-HeFT investigators (2002) Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors. J Am Coll Cardiol 40:1414–1421

    PubMed  CAS  Google Scholar 

  104. Mahle WT, Cuadrado AR, Kirshborn PM, Kanter KR, Simsic JM (2005) Nesiritide in infants and children with congestive heart failure. Pediatr Crit Care Med 6:543– 546

    PubMed  Google Scholar 

  105. Marcus LS, Hart D, Packer M, et al. (1996) Hemodynamic and renal excretory effects of human brain natriuretic peptide infusion in patients with congestive heart failure: a double-blind, placebo-controlled, randomized crossover trial. Circulation 94:3184–3189

    PubMed  CAS  Google Scholar 

  106. Marez D, Legrand M, Sabbagh N, et al. (1997) Ploymorphism of the cytochrome P450 CYP2D6 gene in a European papulation: characterization of 48 mutations and 53 alleles, their frequencies and evolution. Pharmacogenetics 7:193–202

    PubMed  CAS  Google Scholar 

  107. Marino MR, Vachharajani NN (2002) Pharmacokinetics of irbesartan are not altered in special populations. J Cardiovasc Pharmacol 40:112–122

    PubMed  CAS  Google Scholar 

  108. Marshall J, Berkenbosch JW, Russo P, Tobias JD (2004) Preliminary experience with nesiritide in the pediatric population. J Intensive Care Med 19:164–170

    PubMed  Google Scholar 

  109. Martin J, Krum H (2001) Eplerenone (GD Searle & Co.). Curr Opin Invest Drugs 12:521–524

    Google Scholar 

  110. Materson BJ, Reda DJ, Cushman WC (1995) Department of Veterans Affairs single drug therapy of hypertension study. Revised figures and new data. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. Am J Hypertens 8:189–192

    PubMed  CAS  Google Scholar 

  111. McDowell G, Coutie W, Shaw C, et al. (1997) The effect of the neutral endopeptidase inhibitor drug, candoxatril, on circulating levels of two of the most potent vasoactive peptides. Br J Clin Pharmgcol 43:329–332

    CAS  Google Scholar 

  112. !McKelvie RS, Yusuf S, Pericak D, et al; RESOLVD pilot study investigators (1999) Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. Circulation 100:1056–1064

    PubMed  CAS  Google Scholar 

  113. McMurray JJ, Ostergren J, Swedberg K, CHARM et al. investigators and committee (2003) 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 362:772–776

    PubMed  Google Scholar 

  114. McNamara DM, Holubkov R, Janosko K, et al. (2001) Pharmacogenetic interactions between beta-blocker therapy and the angiotensin converting enzyme deletion polymorphism in patients with congestive heart failure. Circulation 103:1644–1648

    PubMed  CAS  Google Scholar 

  115. Micromedex. Spironolactone—drug evaluation. Online healthcare series. (2003, October 12) Available at http://www. micromedex.com/products/hcsonline/

  116. Mills RM, LeJemtel TH, Horton DP, et al. (1999) Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure. J Am Coll Cardiol 34:155–162

    PubMed  CAS  Google Scholar 

  117. Mir TS, Marohn S, Laer S, et al. (2002) Plasma concentrations of N-terminal pro-brain natriuretic peptide in control children from the neonatal to adolescent period and in children with congestive heart failure. Pediatrics 110:e76

    PubMed  Google Scholar 

  118. Moiseyev V, Poder P, Andrejevs N, et al. (2002) Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN). Eur Heart J 23:1422–1432

    PubMed  CAS  Google Scholar 

  119. Mou S, Haudek S, Lequier L, et al. (2002) Myocardial inflammatory activation in children with congenital heart disease. Crit Care Med 30:827–832

    PubMed  Google Scholar 

  120. National Institutes of Health Clinical Trials Web page, http://www.clinicaltrials.gov (accessed 2004, April 30)

  121. Nieminen M, Akkila J, Hasenfuss G, et al. (2000) Hemodynamic and neurohormonal effects of continuous infusion of levosimendan in patients with congestive heart failure. J Am Coll Cardiol 36:1903–1912

    PubMed  CAS  Google Scholar 

  122. Nijwahan N, Nicolosi A, Montgomery M, et al. (1999) Levosimendan enchances cardiac performance after cardio- pulmonary bypass: a prospective, randomized placebo-controlled trial. J Cardiovasc Pharmacol 34:219–228

    Google Scholar 

  123. Northridge DB, Currie PF, Newby DE, et al. (1999) Placebo-controlled comparison of candoxatril, an orally active neutral endopeptidase inhibitor, and captopril in patients with chronic heart failure. Eur J Heart Failure 1:67–72

    CAS  Google Scholar 

  124. Northridge DB, Newby DE, Rooney E, et al. (1999) Comparison of the short-term effects of candoxatril, an orally active neutral endopeptidase inhibitor, and frusemide in the treatment of patients with chronic heart failure. Am Heart J 138:1149–1157

    PubMed  CAS  Google Scholar 

  125. Obayashi M, Yano M, Kohno M, et al. (1997) Dose-dependent effect of ANG II-receptor antagonist on myocyte remodeling in rat cardiac hypertrophy. Am J Physiol 273 (4 pt 2):H1824–H1831

    PubMed  CAS  Google Scholar 

  126. O’Conner CM, Gattis WA, Adams KF, et al. (2003) Tezosentan in patients with acute heart failure and acute coronary syndromes. Results of the Randomized Intravenous Tezosentan Study (RITZ-4). J Am Coll Cardiol 41:1452–1457

    Google Scholar 

  127. O’Conner CM, Gattis WA, Gheorghiade M, et al. (1999) A randomized trial of ecadotril versus placebo in patients with mild to moderate heart failure: the U.S. ecadotril pilot safety study. Am Heart J 138:1140–1148

    Google Scholar 

  128. Ooi H, Colucci WS, Givertz MM (2002) Endothelin mediates increased plumonary vascular tone in patients with failure. Circulation 106:1618–1621

    PubMed  CAS  Google Scholar 

  129. Packer M, Colucci WS, Fisher L, et al. (2003) Development of a comprehensive new end point for the evaluation of new treatments for acute decompensated heart failure: result with levosimendan in the REVIVE-1 study [Abstract]. J Card Failure 9:S61

    Google Scholar 

  130. Pataricza J, Krassoi I, Hohn J, Kun A, Papp JG (2003) Functional channels in the vasodilating mechanism of levosimendan in porcine isolated coronary artery. Cardiovasc Drugs Ther 17:115–121

    PubMed  CAS  Google Scholar 

  131. Patterson JH, Rodgers JE (2003) Expanding role of beta-blockade in the management of chronic heart failure. Pharmacotherapy 23:451–459

    PubMed  CAS  Google Scholar 

  132. Paulus WJ, Shah AM (1999) NO and cardiac diastolic function. Cardiovasc Res 43:595–606

    PubMed  CAS  Google Scholar 

  133. Philipp S, Monti J, Pagel I, et al. (2002) Treatment with darusentan over 21 days improved cGMP generation in patients with chronic heart failure. Clin Sci 103:2495–2535

    Google Scholar 

  134. Pitt B, Poole-Wilson PA, Segal R, et al. (2000) Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomized trial—The losartan heart failure survival study ELITE II. Lancet 355:1582–1587

    PubMed  CAS  Google Scholar 

  135. Pitt B, Reicheck N, Willnebrock R, et al. (2003) Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy. The 4E-left ventricular hypertrophy study. Circulation 108:1831–1838

    PubMed  CAS  Google Scholar 

  136. Pitt B, Reichek N, Metscher B, et al. (2002) Efficacy and safety of eplerenone, enalapril, and eplerenone/enalapril combination therapy in patients with left ventricular hypertrophy [Abstract]. Am J Hypertens 15 (part 2):23A

    Google Scholar 

  137. Pitt B, Remme W, Zannad F, for the EPHESUS study group et al. (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348:1309–1321

    PubMed  CAS  Google Scholar 

  138. Pitt B, Roniker B (1999) Eplerenone, a novel selective aldosterone receptor antagonist (SARA) dose finding study in patients with heart failure [Abstract]. J Am Coll Cardiol 33S188A–33S189A

  139. Pitt B, Segal R, Martinez FA, et al. (1997) Randomised trial of losartan versus captopril in patients greater than 65 with heart failure (evaluation of losartan in the elderly study, ELITE). Lancet 349:747–752

    PubMed  CAS  Google Scholar 

  140. Puddy VF, Amirmansour C, Williams AF, Singer DR (2002) Plasma brain natriuretic peptide as a predictor of haemodynamically significant patent ductus arteriosus in preterm infants. Clin Sci (London) 103:75–77

    CAS  Google Scholar 

  141. Quashning L Ruschitzka F, Shaw S, et al. (2001) Aldosterone receptor antagonism normalizes vascular function in liquorice-induced hypertension. Hypertension 37 (2 pt 2):801–805

    Google Scholar 

  142. Roberston WO (1998) Chemicals, children, and research $’s. Vet Hum Toxicol 40:308–309

    Google Scholar 

  143. Rocha R, Chander PN, Zuckerman A, et al. (1999) Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension 33(1 pt 2) 232–237

    PubMed  CAS  Google Scholar 

  144. Rocha R, Stier CT, Kifor I, et al. (2000) Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. Endocrinology 141:3871–3878

    PubMed  CAS  Google Scholar 

  145. Rockman HA, Wachorst SP, Mao L, Ross J Jr (1994) ANG II receptor blockade prevents ventricular hypertrophy and ANF gene expression with pressure overload in mice. Am J Physiol 226(6 pt 2):H2468–H2475

    Google Scholar 

  146. Roniker B (1997) Eplerenone, a selective antagonist of the aldosterone receptor [Abstract]. Hypertension 30:995

    Google Scholar 

  147. Ross RD, Daniels SR, Schwartz DC, et al. (1987) Plasma norepinephrine levels in infants and childern with congestive heart failure. Am J Cardiol 59:911–914

    PubMed  CAS  Google Scholar 

  148. Rouleau JU Pfeffer MA, Stewart DJ, et al. (2000) Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomized trial. Lancet 356:615–620

    Google Scholar 

  149. Rusconi P, Gomez-Marin O, Rossique-Gonzalez M, et al. (2004) Carvedilol in children with cardiomyopthy: 3-year experience at a single institution. J Heart Lung Transplant 23:832–838

    PubMed  Google Scholar 

  150. Sackner-Bernstein JD, Kowalski M, Fox M, Aaronson K (2005) Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis randomized controlled trials. J Am Med Assoc 293:1900–1905

    CAS  Google Scholar 

  151. Sackner-Bernstein JD, Skopicki HA, Aaronson KD (2005) Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation 111:1487–1491

    PubMed  CAS  Google Scholar 

  152. Sakarcan A, Tenney F, Wilson JT, et al. (2001) The pharmacokinetics of irbesartan in hypertensive children and adolescents. J Clin Pharmacol 41:742–749

    PubMed  CAS  Google Scholar 

  153. Sasaki M, Oki T, Iuchi A, et al. (1996) Relationship between the angiotensin converting enzyme gene polymorphism and the effects of enalapril on left ventricular hypertrophy and impaired diastolic filling in essential: M-mode and pulsed Doppler echocardiographic studies. J Hypertens 14:1403–1408

    PubMed  CAS  Google Scholar 

  154. Sato S, Hassan Talukder M, Sugawara H, et al. (1998) Effects of levosimendan on myocardial contractility and Ca++ transients in aequorin-loaded right ventricular papillary muscles and indo-1-loaded single ventricular cardiomyocytes of the rabbit. J Mol Cell Cardiol 30:1115–1128

    PubMed  CAS  Google Scholar 

  155. Schalcher C, Cotter G, Reisin L, et al. (2001) The dual endothelin receptor antagonist tezosentan acutely improves hemodynamic parameters in patients with advanced heart failure. Am Heart J 142:340–349

    PubMed  CAS  Google Scholar 

  156. Schulze-Neick I, Luther YC, Ewert P, et al. (2004) End stage heart failure with pulmonary hypertension: levosimendan to evaluate for heart transplantation alone versus combined heart–lung transplantation. Transplantation 78:1237–1238

    PubMed  Google Scholar 

  157. Scios, lnc. (2001) NDA 20-920: Natrecor (nesiritide) Cardiovascular and Renal Drugs Advisory Committee briefing document. Food and Drug Administration, Rockville, MD

  158. Segarra G, Medina P, Vila JM, et al. (2002) Increased contraction to noradrenaline by vasopressin in human renal arteries. J Hypertension 20:1373–1379

    CAS  Google Scholar 

  159. Sehra R, Underwood K (2003) Nesiritide improves urine output in severely ill pediatric patients awaiting heart transplant without severe hypotension. J Card Failure 5:254

    Google Scholar 

  160. Serradeil Le-Gal G, Bourrie B, Raufaste D, et al. (1994) Effect of a new, potent, non-peptide V1a vasopressin antagonist, SR 49059, on the binding and mitogenic actiyity of vasopressin on Swiss 3T3 cells. Biochem Pharmacol 47:633–641

    PubMed  CAS  Google Scholar 

  161. Serradeil Le-Gal C, Herbert JM, Delisse C, et al. (1995) Effect of SR-49059, a vasopressin V1a antagonist, on human vascular smooth muscle cells. Am J Physiol 268(1 pt 2):H404–H410

    PubMed  CAS  Google Scholar 

  162. Serradeil-Le Gal C, Villanova G, Boutin M, et al. (1995) Effects of SR 49059, a non-peptide antagonist of vasopressin-induced coronary vasoconstriction in conscious rabbits. Fundam Clin Pharmacol 9:17–24

    PubMed  CAS  Article  Google Scholar 

  163. Serradeil-Le Gal C, Wagnon J, Garcia C, et al. (1993) Biochemical and pharmacological properties of SR 49059, a new, potent, nonpeptide antagonist of rat and human vasopressin V1a receptors. J Clin Invest 92:224–231

    PubMed  CAS  Article  Google Scholar 

  164. Seymour AA, Swerdel JN, Abboa-Offei B (1991) Antihypertensive activity during inhibition of neutral endopeptidase and angiotensin converting enzyme. J Cardiovasc Pharmacol 17:456–465

    PubMed  CAS  Google Scholar 

  165. Shaddy R (2000) Beta-adrenergic blockers in the treatment of pediatric heart failure. Prog Pediatr Cardiol 12:113–118

    PubMed  Google Scholar 

  166. Shaddy RE, Tani LY, Gidding SS, et al. (1999) Beta-blocker treatment of dilated cardiomyopathy with congestive heart failure in children: a multi-institutional experience. J Heart Lung Transplant 18:269–274

    PubMed  CAS  Google Scholar 

  167. Shaddy RE (1998) Beta-blocker therapy in young children with congestive heart failure under consideration for heart transplantation. Am Heart J 136:19–21

    PubMed  CAS  Google Scholar 

  168. Shahinfar S, Cano F, Soffer BA, et al. (2005) A double-blind, dose–response study of losartan in hypertensive children. Am J Hypertens 18(2 pt 1):183–190

    PubMed  CAS  Google Scholar 

  169. Silver MA, Horton DP, Ghali JK, et al. (2002) Effect of nesiritide versus dobutamine on short term outcomes in the treatment of patients with acutely decompensated heart failure. J Am Coll Cardiol 39:798–803

    PubMed  CAS  Google Scholar 

  170. Simsic JM, Reddy VS, Kanter KR, Kirshbom PM, Forbess JM (2004) Use of nesiritide (human B-type natriuretic peptide) in infants following cardigc surgery. Pediatr Cardiol 25(6):668–670

    PubMed  CAS  Google Scholar 

  171. Slawsky M, Colucci W, Gottlieb S, et al. (2000) Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Circulation 102:2222–2227

    PubMed  CAS  Google Scholar 

  172. Smith T, Rosen DA, Russo P, et al. (2005) Nesiritide during extracorporeal membrane oxygenation. Paediatr Anaesth 15:152–157

    PubMed  Google Scholar 

  173. Smyth RL, Weindling AM (1999) Research in children: ethical and scientific aspects. Lancet 354(suppl 2):SII21–SII24

    PubMed  Google Scholar 

  174. Solomon SD, Skali H, Bourgoun M, OVERTURE Investigators et al. (2005) Effect of angiotensin-converting enzyme or vasopeptidase inhibition on ventricular size and function in patients with heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE) echocardiographic study. Am Heart J 150:257–262

    PubMed  CAS  Google Scholar 

  175. Speiker LE, Mitrovic V, Noll G, et al. (2000) Acute hemodynamic and neurohormonal effects of selective ET A receptor blockade in patients with congestive heart failure. J Am Coll Cardiol 35:1745–1752

    Google Scholar 

  176. Spieker LE, Noll G, Ruschitzka FT, Luscher TF (2001) Endothelin receptor antagonists in congestive heart failure: a new therapeutic principle for the future? J Am Coll Cardiol 37:1493–1505

    PubMed  CAS  Google Scholar 

  177. Suda K, Matsumura M, Matsumoto M (2003) Clinical implication of plasma natriuretic peptides in children with ventricular septal defect. Pediatr Int 45:249–254

    PubMed  Google Scholar 

  178. Sudoh T, Kangawa K, Minamino N, Matsuo H (1988) A new natriuretic pepetide in porcine brain. Nature 332:78–81

    PubMed  CAS  Google Scholar 

  179. Sundberg S, Lehtonen L (2000) Haemodynamic interactions between the novel calcium sensitizer levosimendan and isosorbide-5-mononitrate in healthy subjects. Eur J Clin Pharmool 55:793–799

    CAS  Google Scholar 

  180. Sutsch G, Bertel O, Kiowski W (1997) Acute and short-term effects of the nonpeptide endothelin-1 receptor antagonist bosentan in humans. Cardiovasc Drug Ther 10:717–725

    CAS  Google Scholar 

  181. Sutsch G, Kiowski W, Yan XW, et al. (1998) Short term oral endothelin-receptor antagonist therapy in conventionally treated patients with symptomatic severe chronic heart failure. Circulation 98:2262–2268

    PubMed  CAS  Google Scholar 

  182. Tahara A, Saito M, Sugimoto T, et al. (1998) Pharmacologic characterization of YM078, a potent, nonpeptide human vasopressin V1A and Vz recept or antagonist. Naunyn Schmeidebergs Arch Pharmacol 357:63–69

    CAS  Google Scholar 

  183. Tahara A, Saito M, Tsukada J, et al. (1999) Vasopressin increases vascular endothelial growth factor secretion from vascular smooth muscle cells. Eur J Pharmacol 368:89–94

    PubMed  CAS  Google Scholar 

  184. Tahara A, Tomura Y, Wada K, et al. (1997) Effect of YM087, a potent non-peptide vasopressin antogonist on vasopressin-induced hyperplasia and hypertrophy of cultured smooth-muscle cells. J Cardiovasc Pharmacol 30:759–766

    PubMed  CAS  Google Scholar 

  185. Tahara A, Tomura Y, Wada K, et al. (1997) Pharmacologic profile of YM087, a novel potent nonpeptide vasopressin VlA and V2 receptor antagonist, in vitro and vivo. J Pharmacol Exp Ther 282:301–308

    PubMed  CAS  Google Scholar 

  186. Tahara A, Tomura Y, Wada K, et al. (1998) Effect of YM087, a potent nonpeptide vasopressin antagonist, on vasopressin-induced protein synthesis in neonatal rat cardiomyocyte. Cardiovasc Res 38:198–205

    PubMed  CAS  Google Scholar 

  187. Takahashi T, Yamaguchi E, Furya K, et al. (2001) The ACE gene polymorphism and cough threshold for capsaicin after cilazapril usage. Repir Med 95:130–135

    CAS  Google Scholar 

  188. Takeda T, Miyamori I Yoneda T, et al. (1995) Production of aldosterone in isolated rat blood vessels. Hypertension 25:170–173

    PubMed  CAS  Google Scholar 

  189. akeda T, Miyamori I, Yoneda T, et al. (1996) Regulation of aldosterone synthase in human vascular endothelial cells by adrenocorticotropin. J Clin Endocrinol Metab 81:2797–2800

    PubMed  CAS  Google Scholar 

  190. Tanaka H, Suzuki K, Nakahata T, et al. (2004) Combined therapy of enalapril and losartan attenuates histologic progression in immunoglobulin A nephropathy. Pediatr Int 46:576–579

    PubMed  CAS  Google Scholar 

  191. Tassani P, Schad H, Heimisch W, et al. (2002) Effect of the calcium sensitizer levosimendan on the performance of ischaemic myocardium in anaesthetized pigs. Cardiovasc Drugs Ther 16:435–441

    PubMed  CAS  Google Scholar 

  192. Taylor AL, (2005)The African American Heart Failure Trial: a clinical trial Update. Am J Cardiol 10:44–48

    Google Scholar 

  193. Teerlink JR, McMurray JJ, Bourge RC, VERITAS Investigators (2005) Tezosentan in patients with acute heart failure: design of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute Heart Failure Study (VERITAS). Am Heart J 150:46–53

    CAS  Google Scholar 

  194. Thibonnier M, Kilani A, Rahmann M, et al. (1999) Effects of the nonpeptide Vl vasopressin receptor antagonist SR49059 in hypertensive patients. Hypertension 341:1293–1300

    Google Scholar 

  195. Tomura Y, Tahara A, Tsukada, et al. (1999) Pharmacologic profile of orally administered YM087, a vasopressin antagonist, in conscious rats. Clin Exp Pharmacol Physiol 26:399–403

    PubMed  CAS  Google Scholar 

  196. Torre-Amione G (2002) A pilot safety trial of prolonged (48 hour) infusion of the dual endothelin receptor antagonist tezosentan in patients with advanced heart failure. Chest 120:460–466

    Google Scholar 

  197. Torre-Amione G, Kapadia S, Benedict C, et al. (1996) Proinflammatory cytokine levels in depressed left ventricular ejection fraction: a report from the studies of ventricular dysfunction (SOLVD). J Am Coll Card 27:1201–1206

    CAS  Google Scholar 

  198. Torre-Amione G, Young JB, Durand JB, et al. (2001) Hemodynamic effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients with class III to class IV congestive heart failure. Circulation 103:973–980

    PubMed  CAS  Google Scholar 

  199. Tsukada J, Tahara A, Tomura Y, et al. (2001) Effects of YM471, a nonpeptide AVP V(1A) and V(2) receptor antagonist, on human AVP receptor subtypes expressed in CHO cells and oxytocin receptors in human uterine smooth muscle cells. Br J Pharmacol 133:746–754

    PubMed  CAS  Google Scholar 

  200. Tsukada J, Tahara A, Tomura Y, et al. (2002) Effects of YM471, an orally active non-peptide arginine vasopressin receptor antagonist of human vascular smooth muscle cells. J Hypertens 20:1807–1814

    PubMed  Google Scholar 

  201. Tsukada J, Tahara A, Tomura Y, et al. (2002) Pharmacological characterization of YM471, a novel potent vasopressin V(1A) and V(2) receptor antagonist. Eur Pharmacol 446:129–138

    CAS  Google Scholar 

  202. Udleson JE, Smith WB, Hendrix GH, et al. (2001) Acute hemodynamic effects of conivaptan a dual VIA and V2 vasopressin receptor antagonist, in patients with advanced heart failure. Circulation 104:2417–2423

    Google Scholar 

  203. Uhlir O, et al. (1994) Clinical and hemodynamic effects of nebivolol in patients with mild to moderate congestive heart failure. JRF Clinical Research Report NEB = TCH-4

  204. Ukkonen H, Saraste M, Akkila J, et al. (2000) Myocardial efficiency during levosimendan infusion in congestive heart failure. Clin Pharmacol Ther 68:522–531

    PubMed  CAS  Google Scholar 

  205. Ullian ME, Islam MM, Robinson CJ, et al. (1997) Resistance to mineralcorticoids in Wistr–Furth rats. Am J Physiol 272(3 pt 2): H1454–1461

    PubMed  CAS  Google Scholar 

  206. Vachharajani NN, Shyu WC, Smith RA, Greene DS (1998) The effects of age and gender n the pharmacokinetics of irbesartan. Br J Clin Pharmacol 46:611–613

    PubMed  CAS  Google Scholar 

  207. Valjakka-Koskela R, Hirvonen J, Monkkonen J, et al. (2000) Transdermal delivery of levosimendan. Eur J Pharm Sci 11:343–350

    PubMed  CAS  Google Scholar 

  208. Van Geel PP, Pinto YM, Voors AA, et al. (2000) Angiotensin II type 1 receptor A1166C gene polymorphism is associated with an increased response to angiotensin II in human arteries. Hypertension 35:717–721

    PubMed  Google Scholar 

  209. Van Kerckhoven R, Lankhuizen I, van Veghel R, et al. (2002) Chronic vasopressin V(la) but not V(2) receptor antagonism prevents heart failure in chronically infarcted rats. Eur J Pharmical 449:135–141

    Google Scholar 

  210. Vichiendilokkul A, Tran A, Racine E (2003) Nesiritide: A novel approach for acute heart failure. Ann Pharmacother 37:247–258

    PubMed  CAS  Google Scholar 

  211. Virag L, Hala O, Marion A, et al. (1996) Cardiac electrophysiologic effects levosimendan, a new calcium sensitizer. Gen Pharmacol 27:551–556

    PubMed  CAS  Google Scholar 

  212. Wada K, Tahara A, Arai Y, et al. (2002) Effect of the vasopressin receptor antagonist conivaptan in rats with heart failure following myocardial infarction. Eur J Pharmacol 450:169–177

    PubMed  CAS  Google Scholar 

  213. Wahlander H, Westerlind A, Lindstedt G, Lundberg PA, Holmgren D (2005) Increased levels of brain and atrial natriuretic peptides after the first palliative Operation, but not after a bidirectional Glenn anastomosis, in children with functionally univentricular hearts. Cardiol Young 13:268–274

    Google Scholar 

  214. Wang P, Ba ZF, Chaudry IH (1994) Administration of tumor necrosis factor alpha in vivo depresses endothelium-dependent relaxation. Am J Physiol 266:H2535–H2541

    PubMed  CAS  Google Scholar 

  215. Ward MR, Kanellakis P, Ramsey D, et al. (2001) Eplerenone suppresses constrictive remodeling and collagen accumulation after angioplasty in porcine coronary arteries. Circulation 104:467–472

    PubMed  CAS  Google Scholar 

  216. Weber R, Pechere-Bertschi A, Hayoz D, et al. (1997) Effects of SR 49059, a new orally active and specific vasopressin V1 receptor antagonist, on vasopressin-induced vasoconstriction in humans. Hypertension 30:1121–1127

    PubMed  CAS  Google Scholar 

  217. Westheim AS, Bostrom P, Christensen CC, et al. (1999) Hemodynamic and neuroendocrine effects for candoxatril and frusemide in mild stable chronic heart failure. J Am Coll Cardiol 34:l794–1801

    Google Scholar 

  218. White CT, Macpherson CF, Hurley RM, Matsell DG (2003) Antiproteinuric effects of enalapril and losartan: a pilot study. Pediatr Nephrol 18:1038–1043

    PubMed  Google Scholar 

  219. Willienheimer R, Dahlof B, Rydberg E, Erhardt L (1999) AT1-receptor blockers in hypertension and heart failure: clinical experience and future directions. Eur Heart J 20:997–1008

    Google Scholar 

  220. Winkelmann BR (2004) American Heart Association scientific sessions. Expert Opin Invest Drugs 13:435–445

    CAS  Google Scholar 

  221. Winkelman BR, Russ AP, Nauck M, et al. (1999) Angiotensin M235T polymorphism is associated with plasma angiotensinogen and cardiovascular disease. Am Heart J 137:698–705

    Google Scholar 

  222. Wisenbaugh T, Katz T, Davis J, et al. (1993) Long-term (3 month) effects of a new beta-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy. J Am Coll Cardiol 21:1094–1110

    PubMed  CAS  Article  Google Scholar 

  223. Wong W, Mauger D (2004) Treatment of Wilms tumor-related hypertension with losartan and captopril. Pediatr Nephrol 19:805–807

    PubMed  Google Scholar 

  224. Yatsu T, Tomura Y, Tahara A, et al. (1999) Cardiovascular and renal effects of conivaptan hydrochloride (YM087), a vasopressin V1A and V2 receptor antagonist, in dogs with pacing-induced congestive heart failure. Eur J Pharmacol 327:239–246

    Google Scholar 

  225. Yatsu T, Tomura Y, Tahara A, et al. (1997) Pharmacologic profile of YM087, a novel nonpeptide dual vasopressin V1 A and V2 receptor antagonist, in dogs. Eur J Pharmacol 321:225–230

    PubMed  CAS  Google Scholar 

  226. Yatsu T, Tomura Y, Tahara A, et al. (1999) Pharmacology of conivaptan hydrochloride (YM087), a novel vasopressin V1 A/V2 receptor antagonist. Nippon Yakurigaku Zasshi 114 (Suppl): 1l3P–117P

    Google Scholar 

  227. Yatsu T, Kusayama T, Tomura Y, et al. (2002) Effect of conivaptan a combined vasopressin V1A and V2 receptor antagonist, on vasopressin-induced cardiac and hemodynamic changes in anaesthetized dogs. Pharmacol Res 46:375–381

    PubMed  CAS  Google Scholar 

  228. Yokoshiki H, Katsube Y, Sunagawa M, Sperelakis N (1997) Levosimendan, a novel Ca2+ sensitizer, activates the glibenclamide-sensitive K+ channel in rat arterial myocytes. Eur J Pharmacol 333:249–259

    PubMed  CAS  Google Scholar 

  229. Yue TL, Cheng HY, Lysko PG, et al. (1992) Carvedelol, a new vasodilator and beta adrenoreceptor antagonist, is an antioxidant and free radical scavenger. J.Pharmacol Exp Ther 263:92–98

    PubMed  CAS  Google Scholar 

  230. Yusuf S, Pfeffer MA, Swedberg K, et al. (2003) Comittees CHARM investigators and Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme Inhibitors: the CHARM-Added trial. Lancet 362:767–771

    PubMed  Google Scholar 

  231. Zairis MN, Apostolatos C, Anatassiadis F, et al. (2004) Comparison of the effect of levosimendan or dobutamine or placebo in chronic low output decompensated heart failure. Calcium Sensitizer or Inotrope or None in Low Output Heart Failure (CASINO) study. In: Program and abstracts of the European Society of Cardliology, Heart Failure Update 2004; June 12–15, Wroclaw Poland Abstract 273

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  1. Department of Pharmacy, Texas Children’s Hospital, 6621 Fannin Street, MC 2-2510, Houston, TX, 77030, USA

    Brady S. Moffett

  2. Children’s Hospital of Orange County, Orange, CA, 77030, USA

    Anthony C. Chang

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Moffett, B.S., Chang, A.C. Future Pharmacologic Agents for Treatment of Heart Failure in Children. Pediatr Cardiol 27, 533–551 (2006). https://doi.org/10.1007/s00246-006-1289-0

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Keywords

  • Carvedilol
  • Angiotensin Converting Enzyme Inhibitor
  • Levosimendan
  • Nebivolol
  • Eplerenone