The Journal of Heart and Lung Transplantation
Volume 28, Issue 7 , Pages 676-682 , July 2009

Acute Hemodynamic Effects of Intravenous Sildenafil Citrate in Congestive Heart Failure: Comparison of Phosphodiesterase Type-3 and -5 Inhibition

  • Phil Botha, MRCS

      Affiliations

    • Department of Cardiopulmonary Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
    • Corresponding Author InformationReprint requests: Phil Botha, Department of Cardiopulmonary Transplantation, Freeman Hospital, High Heaton, Newcastle upon Tyne, NE7 7DN, UK. Telephone: 0044-191-213-7140. Fax: 0044-191-223-1152
    • ,
  • Gareth Parry, FRCP

      Affiliations

    • Department of Cardiopulmonary Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
    • ,
  • John H. Dark, FRCS

      Affiliations

    • Department of Cardiopulmonary Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
    • ,
  • Guy A. MacGowan, MD, FRCPI

      Affiliations

    • Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom

Received 28 December 2008 ,Revised 11 March 2009 ,Accepted 7 April 2009.

References 

  1. Delgado JF, Conde E, Sanchez V, et al. Pulmonary vascular remodeling in pulmonary hypertension due to chronic heart failure. Eur J Heart Fail. 2005;7:1011–1016
  2. Wallis RM, Corbin JD, Francis SH, Ellis P. Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol. 1999;83:3–12C
  3. Alaeddini J, Uber PA, Park MH, Scott RL, Ventura HO, Mehra MR. Efficacy and safety of sildenafil in the evaluation of pulmonary hypertension in severe heart failure. American Journal of Cardiology. 2004;94:1475–1477
  4. Senzaki H, Smith CJ, Juang GJ, et al. Cardiac phosphodiesterase 5 (cGMP-specific) modulates {beta}-adrenergic signaling in vivo and is down-regulated in heart failure. FASEB J. 2001;15:1718–1726
  5. Loughney K, Hill TR, Florio VA, et al. Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3,′5′-cyclic nucleotide phosphodiesterase. Gene. 1998;216:139–147
  6. Nagendran J, Archer SL, Soliman D, et al. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation. 2007;116:238–248
  7. Das A, Xi L, Kukreja RC. Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis (Essential role of nitric oxide signaling). J Biol Chem. 2005;280:12944–12955
  8. Takimoto E, Belardi D, Tocchetti CG, et al. Compartmentalization of cardiac beta-adrenergic inotropy modulation by phosphodiesterase type 5. Circulation. 2007;115:2159–2167
  9. Borlaug BA, Melenovsky V, Marhin T, Fitzgerald P, Kass DA. Sildenafil inhibits beta-adrenergic-stimulated cardiac contractility in humans. Circulation. 2005;112:2642–2649
  10. Takimoto E, Champion HC, Li M, et al. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med. 2005;11:214–222
  11. Hassan MA, Ketat AF. Sildenafil citrate increases myocardial cGMP content in rat heart, decreases its hypertrophic response to isoproterenol and decreases myocardial leak of creatine kinase and troponin T. BMC Pharmacol. 2005;5:10
  12. Fisher PW, Salloum F, Das A, Hyder H, Kukreja RC. Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity. Circulation. 2005;111:1601–1610
  13. Kojda G, Kottenberg K, Nix P, Schluter KD, Piper HM, Noack E. Low increase in cGMP induced by organic nitrates and nitrovasodilators improves contractile response of rat ventricular myocytes. Circulation research. 1996;78:91–101
  14. Vila-Petroff MG, Younes A, Egan J, Lakatta EG, Sollott SJ. Activation of distinct cAMP-dependent and cGMP-dependent pathways by nitric oxide in cardiac myocytes. Circulation research. 1999;84:1020–1031
  15. Mohan P, Brutsaert DL, Paulus WJ, Sys SU. Myocardial contractile response to nitric oxide and cGMP. Circulation. 1996;93:1223–1229
  16. Martin-Morales A, Haro JM, Beardsworth A, Bertsch J, Kontodimas S, Group E. Therapeutic effectiveness and patient satisfaction after 6 months of treatment with tadalafil, sildenafil, and vardenafil: results from the erectile dysfunction observational study (EDOS). [erratum appears in Eur Urol 2007 Jul;52:304–6] Eur Urol. 2007;51:541–550discussion 550
  17. Sastry BK, Narasimhan C, Reddy NK, Raju BS. Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study. [see comment] J Am Coll Cardiol. 2004;43:1149–1153
  18. Wilkins MR, Paul GA, Strange JW, et al. Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study. [see comment] Am J Respir Crit Care Med. 2005;171:1292–1297
  19. Ghofrani HA, Wiedemann R, Rose F, et al. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. [see comment] Lancet. 2002;360:895–900
  20. Lepore JJ, Dec GW, Zapol WM, Bloch KD, Semigran MJ. Combined administration of intravenous dipyridamole and inhaled nitric oxide to assess reversibility of pulmonary arterial hypertension in potential cardiac transplant recipients. J Heart Lung Transplant. 2005;24:1950
  21. Jackson G, Benjamin N, Jackson N, Allen MJ. Effects of sildenafil citrate on human hemodynamics. Am J Cardiol. 1999;83:13–20C
  22. Angel Gomez-Sanchez M, Saenz De La Calzada C, Escribano Subias P, et al. Pilot assessment of the response of several pulmonary hemodynamic variables to sublingual sildenafil in candidates for heart transplantation. Eur J Heart Fail. 2004;6:615–617
  23. Guazzi M, Tumminello G, Di Marco F, Fiorentini C, Guazzi MD. The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure. J Am Coll Cardiol. 2004;44:2339–2348
  24. Al-Hesayen A, Floras JS, Parker JD. The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure. Eur J Heart Fail. 2006;8:864–868
  25. Forfia PR, Lee M, Tunin RS, Mahmud M, Champion HC, Kass DA. Acute phosphodiesterase 5 inhibition mimics hemodynamic effects of B-type natriuretic peptide and potentiates B-type natriuretic peptide effects in failing but not normal canine heart. J Am Coll Cardiol. 2007;49:1079–1088
  26. Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure (The PROMISE Study Research Group). N Engl J Med. 1991;325:1468–1475
  27. Cuffe MS, Califf RM, Adams KF, et al. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA. 2002;287:1541–1547
  28. MacGowan GA. Clinical overview of the novel inotropic agent toborinone. Expert Opin Investig Drugs. 2000;9:1109–1117
  29. MacGowan GA, Koretsky AP. Inotropic and energetic effects of altering the force-calcium relationship: mechanisms, experimental results, and potential molecular targets. J Cardiac Fail. 2000;6:144–156
  30. Ding B, Abe J, Wei H, et al. Functional role of phosphodiesterase 3 in cardiomyocyte apoptosis: implication in heart failure. Circulation. 2005;111:2469–2476
  31. Sackner-Bernstein JD, Kowalski M, Fox M, Aaronson K. Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. JAMA. 2005;293:1900–1905

 This study was funded by a grant from the Newcastle Hospitals NHS Trust Special Trustees.

PII: S1053-2498(09)00235-6

doi: 10.1016/j.healun.2009.04.013

The Journal of Heart and Lung Transplantation
Volume 28, Issue 7 , Pages 676-682 , July 2009

Article Tools

* Image Usage & Resolution