Journal of Cardiac Failure
Volume 15, Issue 3 , Pages 182-190 , April 2009

Intravenous Recombinant Human Relaxin in Compensated Heart Failure: A Safety, Tolerability, and Pharmacodynamic Trial

  • Thomas Dschietzig, MD

      Affiliations

    • Department of Cardiology and Angiology, Charité – University Medicine Berlin, Campus Mitte
    • Corresponding Author InformationReprint requests: Thomas Dschietzig, Medizinische Klinik m. S. Kardiologie und Angiologie, Charité – Universitätsmedizin Berlin, Campus Mitte, Schumannstr. 20/21, 10117 Berlin, Germany. Tel.: 0049-30-450 613 418; Fax: 0049-30-450 513 930.
    • ,
  • Sam Teichman, MD

      Affiliations

    • Corthera, Inc., San Mateo, CA
    • ,
  • Elaine Unemori, MD

      Affiliations

    • Corthera, Inc., San Mateo, CA
    • ,
  • Susy Wood

      Affiliations

    • Corthera, Inc., San Mateo, CA
    • ,
  • Julia Boehmer

      Affiliations

    • Department of Cardiology and Angiology, Charité – University Medicine Berlin, Campus Mitte
    • ,
  • Christoph Richter, MD

      Affiliations

    • Department of Cardiology and Angiology, Charité – University Medicine Berlin, Campus Mitte
    • ,
  • Gert Baumann, MD

      Affiliations

    • Department of Cardiology and Angiology, Charité – University Medicine Berlin, Campus Mitte
    • ,
  • Karl Stangl, MD

      Affiliations

    • Department of Cardiology and Angiology, Charité – University Medicine Berlin, Campus Mitte

Received 17 September 2008 ,Revised 22 January 2009 ,Accepted 28 January 2009.

References 

  1. Allen LA, O'Connor CM. Management of acute decompensated heart failure. CMAJ. 2007;176:797–805
  2. Nieminen MS, Bohm M, Cowie MR, et al. Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology. Eur Heart J. 2005;26:384–416
  3. Conrad KP, Novak J. Emerging role of relaxin in renal and cardiovascular function. Am J Physiol Regul Integr Comp Physiol. 2004;287:R250–R261
  4. Dschietzig T, Richter C, Bartsch C, et al. The pregnancy hormone relaxin is a player in human heart failure. FASEB J. 2001;15:2187–2195
  5. Dschietzig T, Bartsch C, Baumann G, Stangl K. Relaxin-a pleiotropic hormone and its emerging role for experimental and clinical therapeutics. Pharmacol Ther. 2006;112:38–56
  6. Danielson LA, Kercher LJ, Conrad KP. Impact of gender and endothelin on renal vasodilation and hyperfiltration induced by relaxin in conscious rats. Am J Physiol Regul Integr Comp Physiol. 2000;279:R1298–R1304
  7. Danielson LA, Conrad KP. Time course and dose response of relaxin-mediated renal vasodilation, hyperfiltration, and changes in plasma osmolality in conscious rats. J Appl Physiol. 2003;95:1509–1514
  8. Dschietzig T, Bartsch C, Richter C, Laule M, Baumann G, Stangl K. Relaxin, a pregnancy hormone, is a functional endothelin-1 antagonist: attenuation of endothelin-1-mediated vasoconstriction by stimulation of endothelin type-B receptor expression via ERK-1/2 and nuclear factor-kappaB. Circ Res. 2003;92:32–40
  9. Jeyabalan A, Novak J, Danielson LA, Kerchner LJ, Opett SL, Conrad KP. Essential role for vascular gelatinase activity in relaxin-induced renal vasodilation, hyperfiltration, and reduced myogenic reactivity of small arteries. Circ Res. 2003;93:1249–1257
  10. Novak J, Danielson LA, Kerchner LJ, et al. Relaxin is essential for renal vasodilation during pregnancy in conscious rats. J Clin Invest. 2001;107:1469–1475
  11. Debrah DO, Conrad KP, Jeyabalan A, Danielson LA, Shroff SG. Relaxin increases cardiac output and reduces systemic arterial load in hypertensive rats. Hypertension. 2005;46:745–750
  12. Seibold JR, Korn JH, Simms R, et al. Recombinant human relaxin in the treatment of scleroderma. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000;132:871–879
  13. Debrah DO, Conrad KP, Danielson LA, Shroff SG. Effects of Relaxin on systemic arterial hemodynamics and mechanical properties in conscious rats: sex dependency and dose response. J Appl Physiol. 2005;98:1013–1020
  14. Unemori EN, Amento EP. Relaxin modulates synthesis and secretion of procollagenase and collagen by human dermal fibroblasts. J Biol Chem. 1990;265:10681–10685
  15. Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation. 2005;111:1487–1491
  16. Smith MC, Danielson LA, Conrad KP, Davison JM. Influence of recombinant human relaxin on renal hemodynamics in healthy volunteers. J Am Soc Nephrol. 2006;17:3192–3197

 Sponsored by Corthera, Inc. S.T., E.U., and S.W. are employees of Corthera.

PII: S1071-9164(09)00030-X

doi: 10.1016/j.cardfail.2009.01.008

Journal of Cardiac Failure
Volume 15, Issue 3 , Pages 182-190 , April 2009

Article Tools

* Image Usage & Resolution