Abstract Title:

Antioxidant treatment attenuates pulmonary arterial hypertension-induced heart failure.

Abstract Source:

Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H1038-47. Epub 2010 Jan 8. PMID: 20061549

Abstract Author(s):

Everaldo M Redout, Annette van der Toorn, Marian J Zuidwijk, Cees W A van de Kolk, Cees J A van Echteld, René J P Musters, Cornelis van Hardeveld, Walter J Paulus, Warner S Simonides

Article Affiliation:

Institute for Cardiovascular Research, VU Univ. Medical Center Amsterdam, The Netherlands.

Abstract:

ROS have been implicated in the development of pathological ventricular hypertrophy and the ensuing contractile dysfunction. Using the rat monocrotaline (MCT) model of pulmonary arterial hypertension (PAH), we recently reported oxidative stress in the failing right ventricle (RV) with no such stress in the left ventricle of the same hearts. We used the antioxidant EUK-134 to assess the role of ROS in the pathological remodeling and dysfunction of the RV. PAH was induced by an injection of MCT (80 mg/kg, day 0), treatment with EUK-134 (25 mg/kg, once every 2 days) of control and MCT-injected animals [congestive heart failure (CHF) group] was started on day 10, and animals were analyzed on day 22. EUK-134 treatment of the CHF group attenuated cardiomyocyte hypertrophy and associated changes in mRNA expression (myosin heavy chain-beta and deiodinase type 3). It also reduced RV oxidative stress and proapoptotic signaling and prevented interstitial fibrosis. Cardiac MRI showed that ROS scavenging did not affect the 37% increase in end-diastolic volume of the RV in the CHF relative to the control group, but the threefold increase in end-systolic volume was reduced by 42% in the EUK-134-treated CHF group. The improved systolic function was confirmed using echocardiography by an assessment of tricuspid annular plane systolic excursion. These data indicate an important role of ROS in RV cardiomyocyte hypertrophy and contractile dysfunction due to PAH and show the potential of EUK-class antioxidants as complementary therapeutics in the treatment of RV dysfunction in PAH.

Study Type : Animal Study

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