Skip to main content Accessibility help

Effects of chronic treprostinil treatment on experimental right heart hypertrophy and failure

  • Sofie Axelgaard (a1), Sarah Holmboe (a1), Steffen Ringgaard (a2), Thomas K. Hillgaard (a1), Stine Andersen (a1), Mona S. Hansen (a1), Asger Andersen (a1) and Jens E. Nielsen-Kudsk (a1)...



Right heart function is an important predictor of morbidity and mortality in pulmonary arterial hypertension and many CHD. We investigated whether treatment with the prostacyclin analogue treprostinil could prevent pressure overload-induced right ventricular hypertrophy and failure.


Male Wistar rats were randomised to severe pulmonary trunk banding with a 0.5-mm banding clip (n=41), moderate pulmonary trunk banding with a 0.6-mm banding clip (n=36), or sham procedure (n=10). The banded rats were randomised to 6 weeks of treatment with a moderate dose of treprostinil (300 ng/kg/minute), a high dose of treprostinil (900 ng/kg/minute), or vehicle.


Pulmonary trunk banding effectively induced hypertrophy, dilatation, and decreased right ventricular function. The severely banded animals presented with decompensated heart failure with extracardial manifestations. Treatment with treprostinil neither reduced right ventricular hypertrophy nor improved right ventricular function.


In the pulmonary trunk banding model of pressure overload-induced right ventricular hypertrophy and failure, moderate- and high-dose treatment with treprostinil did not improve right ventricular function neither in compensated nor in decompensated right heart failure.


Corresponding author

Correspondence to: J. E. Nielsen-Kudsk, MD, DMSc, Department of Cardiology, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, 8200 Aarhus N, Denmark. Tel: +45 7845 2024; Fax: +45 7845 2117; E-mail:


Hide All
1. van Wolferen, SA, Marcus, JT, Boonstra, A, et al. Prognostic value of right ventricular mass, volume and function in idiopathic pulmonary arterial hypertension. Eur Heart J 2007; 28: 12501257.
2. Chin, KM, Kim, NHS, Rubin, LJ. The right ventricle in pulmonary hypertension. Coron Artery Dis 2005; 16: 1318.
3. Sandoval, J, Bauerle, O, Palomar, A, et al. Survival in primary pulmonary hypertension. Validation of a prognostic equation. Circulation 1994; 89: 17331744.
4. Apostolakis, D, Konstantinides, D. The right ventricle in health and disease: insights into physiology, pathophysiology and diagnostic management. Cardiology 2012; 121: 263273.
5. Humbert, M, Sitbon, O, Chaouat, A, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010; 122: 156163.
6. van der Bom, T, Winter, MM, Bouma, BJ, et al. The effect of valsartan on the systemic right ventricular function: a double-blind randomized placebo-controlled pilot trial. Circulation 2013; 127: 322330.
7. Galié, N, Hoeper, MM, Humbert, M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2009; 34: 12191263.
8. Waxman, AB, Zamanian, RT. Pulmonary arterial hypertension: new insights into the optimal role of current and emerging prostacyclin therapies. Am J Cardiol 2013; 111(Suppl): 1A16A; quiz 17A–19A.
9. Schermuly, RT, Kreisselmeier, KP, Ghofrani, HA, et al. Antiremodeling effects of iloprost and the dual-selective phosphodiesterase 3/4 inhibitor tolafentrine in chronic experimental pulmonary hypertension. Circ Res 2004; 94: 11011108.
10. Holmboe, S, Andersen, A, Vildbrad, MD, Nielsen, JM, Ringgaard, S, Nielsen-Kudsk, JE. Iloprost improves ventricular function in the hypertrophic and functionally impaired right heart by direct stimulation. Pulm Circ 2013; 3: 870879.
11. Andersen, S, Schultz, JG, Andersen, A, et al. Effects of bisoprolol and losartan treatment in the hypertrophic and failing right heart. J Card Fail 2014; 20: 864873.
12. Schou, UK, Peters, CD, Wan Kim, S, Frokiaer, J, Nielsen, S. Characterization of a rat model of right-sided heart failure induced by pulmonary trunk banding. J Exp Anim Sci 2007; 43: 237254.
13. Andersen, A, Nielsen, JM, Peters, CD, Schou, UK, Sloth, E, Nielsen-Kudsk, JE. Effects of phosphodiesterase-5-inhibition by sildenafil in the pressure overloaded right heart. Eur J Heart Fail 2008; 10: 11581165.
14. Andersen, A, Nielsen, JM, Holmboe, S, Vildbrad, MD, Nielsen-Kudsk, JE. The effects of cyclic guanylate cyclase stimulation on right ventricular hypertrophy and failure alone and in combination with phosphodiesterase-5 inhibition. J Cardiovasc Pharmacol 2013; 62: 167173.
15. Ghio, S, Recusani, F, Klersy, C, et al. Prognostic usefulness of the tricuspid annular plane systolic excursion in patients with congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy. Am J Cardiol 2000; 85: 837842.
16. Haddad, F, Ashley, E, Michelakis, ED. New insights for the diagnosis and management of right ventricular failure, from molecular imaging to targeted right ventricular therapy. Curr Opin Cardiol 2010; 25: 131140.
17. Bogaard, HJ. The right ventricle under pressure. Chest 2009; 135: 794804.
18. Lowes, BD, Minobe, W, Abraham, WT, et al. Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium. J Clin Invest 1997; 100: 23152324.
19. Sano, M, Minamino, T, Toko, H, et al. p53-Induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload. Nature 2007; 446: 444448.
20. Nagaya, N, Nishikimi, T, Uematsu, M, et al. Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. J Cardiol 2001; 37: 110111.
21. van Albada, ME, van Veghel, R, Cromme-Dijkhuis, AH, Schoemaker, RG, Berger, RM. Treprostinil in advanced experimental pulmonary hypertension: beneficial outcome without reversed pulmonary vascular remodeling. J Cardiovasc Pharmacol 2006; 48: 249254.
22. Gomez-Arroyo, J, Sakagami, M, Syed, AA, et al. Iloprost reverses established fibrosis in experimental right ventricular failure. Eur Respir J 2015; 45: 449462.
23. Orie, NN, Ledwozyw, A, Williams, DJ, Whittle, BJ, Clapp, LH. Differential actions of the prostacyclin analogues treprostinil and iloprost and the selexipag metabolite, MRE-269 (ACT-333679) in rat small pulmonary arteries and veins. Prostaglandins Other Lipid Mediat 2013; 106: 17.
24. Clapp, LH, Finney, P, Turcato, S, Tran, S, Rubin, LJ, Tinker, A. Differential effects of stable prostacyclin analogs on smooth muscle proliferation and cyclic AMP generation in human pulmonary artery. Am J Respir Cell Mol Biol 2002; 26: 194201.
25. Gomberg-Maitland, M, Tapson, VF, Benza, RL, et al. Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. Am J Respir Crit Care Med 2005; 172: 15861589.
26. van Albada, ME, Berger, RM, Niggebrugge, M, van Veghel, R, Cromme-Dijkhuis, AH, Schoemaker, RG. Prostacyclin therapy increases right ventricular capillarisation in a model for flow-associated pulmonary hypertension. Eur J Pharmacol 2006; 549: 107116.
27. Pettersen, E, Helle-Valle, T, Edvardsen, T, et al. Contraction pattern of the systemic right ventricle shift from longitudinal to circumferential shortening and absent global ventricular torsion. J Am Coll Cardiol 2007; 49: 24502456.
28. Fontana, M, Olschewski, H, Olschewski, A, Schlüter, KD. Treprostinil potentiates the positive inotropic effect of catecholamines in adult rat ventricular cardiomyocytes. Br J Pharmacol 2007; 151: 779786.


Related content

Powered by UNSILO
Type Description Title
Supplementary materials

Axelgaard supplementary material
Axelgaard supplementary material

 PDF (2.2 MB)
2.2 MB

Effects of chronic treprostinil treatment on experimental right heart hypertrophy and failure

  • Sofie Axelgaard (a1), Sarah Holmboe (a1), Steffen Ringgaard (a2), Thomas K. Hillgaard (a1), Stine Andersen (a1), Mona S. Hansen (a1), Asger Andersen (a1) and Jens E. Nielsen-Kudsk (a1)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.