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

Published online by Cambridge University Press:  18 April 2016

Sofie Axelgaard ,
Sarah Holmboe ,
Steffen Ringgaard ,
Thomas K. Hillgaard ,
Stine Andersen ,
Mona S. Hansen ,
Asger Andersen  and
Jens E. Nielsen-Kudsk
Sofie Axelgaard
Affiliation:
Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
Sarah Holmboe
Affiliation:
Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
Steffen Ringgaard
Affiliation:
The MR Centre, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
Thomas K. Hillgaard
Affiliation:
Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
Stine Andersen
Affiliation:
Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
Mona S. Hansen
Affiliation:
Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
Asger Andersen
Affiliation:
Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
Jens E. Nielsen-Kudsk*
Affiliation:
Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
*
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: [email protected]
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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Right ventricular dysfunctionpulmonary hypertensionprostacyclin
Type
Original Articles
Information
Cardiology in the Young , Volume 27 , Issue 1 , January 2017 , pp. 90 - 100
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Copyright
© Cambridge University Press 2016 

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