|
|
||||||||||
|
J Am Coll Cardiol, 2004; 44:1488-1496, doi:10.1016/j.jacc.2004.06.060 © 2004 by the American College of Cardiology Foundation |

Department of Internal Medicine, University Hospital Giessen, Giessen, Germany
Manuscript received April 21, 2004; revised manuscript received May 26, 2004, accepted June 7, 2004.
* Reprint requests and correspondence: Dr. Friedrich Grimminger, Department of Internal Medicine, University Hospital Giessen, Klinikstrasse 36, 35392 Giessen, Germany (Email: friedrich.grimminger{at}innere.med.uni-giessen.de).
OBJECTIVES: We sought to compare the short-termimpact of three different phosphodiesterase-5 (PDE5) inhibitors on pulmonary and systemic hemodynamics and gas exchange parameters in patients with pulmonary arterial hypertension (PAH).
BACKGROUND: The PDE5 inhibitor sildenafil has been reported to cause pulmonary vasodilation in patients with PAH. Vardenafil and tadalafil are new PDE5 inhibitors, recently being approved for the treatment of erectile dysfunction.
METHODS: Sixty consecutive PAH patients (New York Heart Association functional class II to IV) who underwent right heart catheterization received short-term nitric oxide (NO) inhalation and were subsequently assigned to oral intake of 50 mg sildenafil (n = 19), 10 mg (n = 7) or 20 mg (n = 9) vardenafil, or 20 mg (n = 9), 40 mg (n = 8), or 60 mg (n = 8) tadalafil. Hemodynamics and changes in oxygenation were assessed over a subsequent 120-min observation period.
RESULTS: All three PDE5 inhibitors caused significant pulmonary vasorelaxation, with maximum effects being obtained after 40 to 45 min (vardenafil), 60 min (sildenafil), and 75 to 90 min (tadalafil). Sildenafil and tadalafil, but not vardenafil, caused a significant reduction in the pulmonary to systemic vascular resistance ratio. Significant improvement in arterial oxygenation (equally to NO inhalation) was only noted with sildenafil.
CONCLUSIONS: In PAH patients, the three PDE5 inhibitors differ markedly in their kinetics of pulmonary vasorelaxation (most rapid effect by vardenafil), their selectivity for the pulmonary circulation (sildenafil and tadalafil, but not vardenafil), and their impact on arterial oxygenation (improvement with sildenafil only). Careful evaluation of each new PDE5 inhibitor, when being considered for PAH treatment, has to be undertaken, despite common classification as PDE5 inhibitors.
| |||||||||||
This article has been cited by other articles:
![]() |
M. R. Wilkins, J. Wharton, F. Grimminger, and H. A. Ghofrani Phosphodiesterase inhibitors for the treatment of pulmonary hypertension Eur. Respir. J., July 1, 2008; 32(1): 198 - 209. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. E. Wrishko, J. Dingemanse, A. Yu, C. Darstein, D. L. Phillips, and M. I. Mitchell Pharmacokinetic Interaction Between Tadalafil and Bosentan in Healthy Male Subjects J. Clin. Pharmacol., May 1, 2008; 48(5): 610 - 618. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Lubamba, H. Lecourt, J. Lebacq, P. Lebecque, H. De Jonge, P. Wallemacq, and T. Leal Preclinical Evidence that Sildenafil and Vardenafil Activate Chloride Transport in Cystic Fibrosis Am. J. Respir. Crit. Care Med., March 1, 2008; 177(5): 506 - 515. [Abstract] [Full Text] [PDF] |
||||
![]() |
L Guidetti, G P Emerenziani, M C Gallotta, F Pigozzi, L Di Luigi, and C Baldari Effect of tadalafil on anaerobic performance indices in healthy athletes Br. J. Sports Med., February 1, 2008; 42(2): 130 - 133. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Nagendran, S. L. Archer, D. Soliman, V. Gurtu, R. Moudgil, A. Haromy, C. St. Aubin, L. Webster, I. M. Rebeyka, D. B. Ross, et al. Phosphodiesterase Type 5 Is Highly Expressed in the Hypertrophied Human Right Ventricle, and Acute Inhibition of Phosphodiesterase Type 5 Improves Contractility Circulation, July 17, 2007; 116(3): 238 - 248. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Takaoka, J. L. Faul, and R. Doyle Current Therapies for Pulmonary Arterial Hypertension Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2007; 11(2): 137 - 148. [Abstract] [PDF] |
||||
![]() |
R. T. Schermuly, S. S. Pullamsetti, G. Kwapiszewska, R. Dumitrascu, X. Tian, N. Weissmann, H. A. Ghofrani, C. Kaulen, T. Dunkern, C. Schudt, et al. Phosphodiesterase 1 Upregulation in Pulmonary Arterial Hypertension: Target for Reverse-Remodeling Therapy Circulation, May 1, 2007; 115(17): 2331 - 2339. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Mukhopadhyay, M. Sharma, S. Ramakrishnan, J. Yusuf, M. D. Gupta, N. Bhamri, V. Trehan, and S. Tyagi Phosphodiesterase-5 Inhibitor in Eisenmenger Syndrome: A Preliminary Observational Study Circulation, October 24, 2006; 114(17): 1807 - 1810. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Fesler, A. Pagnamenta, B. Rondelet, F. Kerbaul, and R. Naeije Effects of sildenafil on hypoxic pulmonary vascular function in dogs J Appl Physiol, October 1, 2006; 101(4): 1085 - 1090. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. A. Ghofrani, R. Voswinckel, F. Reichenberger, N. Weissmann, R. T. Schermuly, W. Seeger, and F. Grimminger Hypoxia- and non-hypoxia-related pulmonary hypertension - Established and new therapies Cardiovasc Res, October 1, 2006; 72(1): 30 - 40. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Distler and A. Pignone Pulmonary arterial hypertension and rheumatic diseases--from diagnosis to treatment Rheumatology, October 1, 2006; 45(suppl_4): iv22 - iv25. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. K. Trow Clinical Year in Review II: Occupational Lung Disease, Pulmonary Vascular Disease, Bronchiectasis, and Chronic Obstructive Pulmonary Disease Proceedings of the ATS, September 1, 2006; 3(7): 557 - 560. [Full Text] [PDF] |
||||
![]() |
S. Jaillard, B. Larrue, P. Deruelle, A. Delelis, T. Rakza, G. Butrous, and L. Storme Effects of Phosphodiesterase 5 Inhibitor on Pulmonary Vascular Reactivity in the Fetal Lamb. Ann. Thorac. Surg., March 1, 2006; 81(3): 935 - 942. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. M. Hoeper and L. J. Rubin Update in pulmonary hypertension 2005. Am. J. Respir. Crit. Care Med., March 1, 2006; 173(5): 499 - 505. [Full Text] [PDF] |
||||
![]() |
E. B. Lobato, T. Beaver, J. Muehlschlegel, D. S. Kirby, C. Klodell, and A. Sidi Treatment with phosphodiesterase inhibitors type III and V: milrinone and sildenafil is an effective combination during thromboxane-induced acute pulmonary hypertension Br. J. Anaesth., March 1, 2006; 96(3): 317 - 322. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. R. Klinger, S. Thaker, J. Houtchens, I. R. Preston, N. S. Hill, and H. W. Farber Pulmonary hemodynamic responses to brain natriuretic Peptide and sildenafil in patients with pulmonary arterial hypertension. Chest, February 1, 2006; 129(2): 417 - 425. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. M. Tsai, M. W. Turrentine, B. C. Sheridan, M. Wang, A. C. Fiore, J. W. Brown, and D. R. Meldrum Differential Effects of Phosphodiesterase-5 Inhibitors on Hypoxic Pulmonary Vasoconstriction and Pulmonary Artery Cytokine Expression Ann. Thorac. Surg., January 1, 2006; 81(1): 272 - 278. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Fung, R. R. Fiscus, A. P. C. Yim, G. D. Angelini, and A. A. Arifi The Potential Use of Type-5 Phosphodiesterase Inhibitors in Coronary Artery Bypass Graft Surgery Chest, October 1, 2005; 128(4): 3065 - 3073. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. M. Hoeper From the authors Eur. Respir. J., July 1, 2005; 26(1): 180 - 181. [Full Text] [PDF] |
||||
![]() |
A. J Lee, T. B Chiao, and M. P Tsang Sildenafil for Pulmonary Hypertension Ann. Pharmacother., May 1, 2005; 39(5): 869 - 884. [Abstract] [Full Text] [PDF] |
||||
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |