title: Dehydroepiandrosterone reverses chronic hypoxia/reoxygenation-induced right ventricular dysfunction in rats.
abstract: Dehydroepiandrosterone (DHEA) prevents chronic hypoxia-induced pulmonary hypertension and associated right ventricle dysfunction in rats. In this animal model, reoxygenation following hypoxia reverses pulmonary hypertension but not right ventricle dysfunction. We thus studied the effect of DHEA on the right ventricle after reoxygenation, i.e. after a normoxic recovery phase secondary to chronic hypoxia in rats. Right ventricle function was assessed in vivo by Doppler echocardiography and in vitro by the isolated perfused heart technique in three groups of animals: control, recovery (21 days of hypoxia followed by 21 days of normoxia) and recovery DHEA (30 mg · kg(-1) every 2 days during the recovery phase). Right ventricle tissue was assessed by optical and electron microscopy. DHEA abolished right ventricle diastolic dysfunction, as the echographic E wave remained close to that of controls (mean ± SD 76.5 ± 2.4 and 79.7 ± 1.7 cm · s(-1), respectively), whereas it was diminished to 40.3 ± 3.7 in the recovery group. DHEA also abolished right ventricle systolic dysfunction, as shown by the inhibition of the increase in the slope of the pressure-volume curve in isolated heart. The DHEA effect was related to cardiac myocytes proliferation. In conclusion, DHEA prevents right ventricle dysfunction in this animal model by preventing cardiomyocyte alteration.
authors.affiliation: Centre de Recherche Cardio-Thoracique U 1045, INSERM U 1045, U 688 and U 1034, INSERM U 1045, U 688 and U 1034, Bordeaux Cedex, France. edumasdlr@gmail.com
authors.forename: Eric
authors.initials: E
authors.lastname: Dumas de La Roque
authors.forename: Nadège
authors.initials: N
authors.lastname: Bellance
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Rossignol
authors.forename: Hugues
authors.initials: H
authors.lastname: Begueret
authors.forename: Marie
authors.initials: M
authors.lastname: Billaud
authors.forename: Pierre
authors.initials: P
authors.lastname: dos Santos
authors.forename: Thomas
authors.initials: T
authors.lastname: Ducret
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.forename: Diana
authors.initials: D
authors.lastname: Dahan
authors.forename: David
authors.initials: D
authors.lastname: Ramos-Barbón
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Amor-Carro
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Savineau
authors.forename: Michael
authors.initials: M
authors.lastname: Fayon
mesh_terms: D000818:Animals; D017209:Apoptosis; D050882:CREB-Binding Protein / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004452:Echocardiography; D015150:Echocardiography, Doppler / Q000379:methods; D000860:Hypoxia / Q000628:therapy*; D008297:Male; D008853:Microscopy / Q000379:methods; D008854:Microscopy, Electron / Q000379:methods; D008928:Mitochondria / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D018497:Ventricular Dysfunction, Right / Q000628:therapy*
chemical_list: D003687:Dehydroepiandrosterone; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D010100:Oxygen