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Inotropic Effects of Prostacyclins on the Right Ventricle Are Abolished in Isolated Rat Hearts With Right-Ventricular Hypertrophy and Failure

Holmboe, S; Andersen, A; Johnsen, J; Nielsen, JM; Nørregaard, R; Bøtker, HE; Clapp, LH; (2017) Inotropic Effects of Prostacyclins on the Right Ventricle Are Abolished in Isolated Rat Hearts With Right-Ventricular Hypertrophy and Failure. Journal of Cardiovascular Pharmacology , 69 (1) pp. 1-12. 10.1097/FJC.0000000000000435. Green open access

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Abstract

BACKGROUND: Prostacyclin mimetics are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostanoids on right-ventricular (RV) function are unknown. We aimed to investigate the direct effects of prostacyclin mimetics on RV function in hearts with and without RV hypertrophy and failure. METHODS: Wistar rats were subjected to pulmonary trunk banding to induce compensated RV hypertrophy (n = 32) or manifest RV failure (n = 32). Rats without banding served as healthy controls (n = 30). The hearts were excised and perfused in a Langendorff system and subjected to iloprost, treprostinil, epoprostenol, or MRE-269 in increasing concentrations. The effect on RV function was evaluated using a balloon-tipped catheter inserted into the right ventricle. RESULTS: In control hearts, iloprost, treprostinil, and MRE-269 improved RV function. The effect was, however, absent in hearts with RV hypertrophy and failure. Treprostinil and MRE-269 even impaired RV function in hearts with manifest RV failure. CONCLUSIONS: Iloprost, treprostinil, and MRE-269 improved RV function in the healthy rat heart. RV hypertrophy abolished the positive inotropic effect, and in the failing right ventricle, MRE-269 and treprostinil impaired RV function. This may be related to changes in prostanoid receptor expression and reduced coronary flow reserve in the hypertrophic and failing right ventricle.

Type: Article
Title: Inotropic Effects of Prostacyclins on the Right Ventricle Are Abolished in Isolated Rat Hearts With Right-Ventricular Hypertrophy and Failure
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/FJC.0000000000000435
Publisher version: http://dx.doi.org/10.1097/FJC.0000000000000435
Language: English
Additional information: © 2017 Wolters Kluwer Health, Inc. All rights reserved. This is a non-final version of an article published in final form Holmboe, S; Andersen, A; Johnsen, J; Nielsen, JM; Nørregaard, R; Bøtker, HE; Clapp, LH; (2017) Inotropic Effects of Prostacyclins on the Right Ventricle Are Abolished in Isolated Rat Hearts With Right-Ventricular Hypertrophy and Failure. Journal of Cardiovascular Pharmacology , 69 (1) pp. 1-12. 10.1097/FJC.0000000000000435.
Keywords: Prostacyclin, contractility, right-ventricular failure, prostanoid receptors, pulmonary arterial hypertension
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/1517858
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