title: Angiotensin II-converting enzyme inhibition improves survival, ventricular remodeling, and myocardial energetics in experimental aortic regurgitation.
abstract: BACKGROUND
  Aortic valve regurgitation (AR) is a volume-overload disease causing severe eccentric left ventricular (LV) hypertrophy and eventually heart failure. There is currently no approved drug to treat patients with AR. Many vasodilators including angiotensin-converting enzyme inhibitors have been evaluated in clinical trials, but although some results were promising, others were inconclusive. Overall, no drug has yet been able to improve clinical outcome in AR and the controversy remains. We have previously shown in an animal model that captopril (Cpt) reduced LV hypertrophy and protected LV systolic function, but we had not evaluated the clinical outcome. This protocol was designed to evaluate the effects of a long-term Cpt treatment on survival in the same animal model of severe aortic valve regurgitation.
  
  
  RESULTS
  Forty Wistar rats with AR were treated or untreated with Cpt (1 g/L in drinking water) for a period of 7 months to evaluate survival, myocardial remodeling, and function by echocardiography as well as myocardial metabolism by µ positron emission tomography scan. Survival was significantly improved in Cpt-treated animals with a survival benefit visible as soon as after 4 months of treatment. Cpt reduced LV dilatation and LV hypertrophy. It also significantly improved the myocardial metabolic profile by restoring the level of fatty acids metabolic enzymes and use.
  
  
  CONCLUSIONS
  In a controlled animal model of pure severe aortic valve regurgitation, Cpt treatment reduced LV remodeling and LV hypertrophy and improved myocardial metabolic profile and survival. These results support the need to reevaluate the role of angiotensin-converting enzyme inhibitors in humans with AR in a large, carefully designed prospective clinical trial.
authors.affiliation: Groupe de Recherche en Valvulopathies, Centre de Recherche, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, Canada.
authors.forename: Marie
authors.initials: M
authors.lastname: Arsenault
authors.forename: Adnane
authors.initials: A
authors.lastname: Zendaoui
authors.forename: Elise
authors.initials: E
authors.lastname: Roussel
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Drolet
authors.forename: Wahiba
authors.initials: W
authors.lastname: Dhahri
authors.forename: Audrey
authors.initials: A
authors.lastname: Grenier
authors.forename: Suzanne
authors.initials: S
authors.lastname: Gascon
authors.forename: Otman
authors.initials: O
authors.lastname: Sarrhini
authors.forename: Jacques A
authors.initials: JA
authors.lastname: Rousseau
authors.forename: Roger
authors.initials: R
authors.lastname: Lecomte
authors.forename: Jacques
authors.initials: J
authors.lastname: Couet
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001022:Aortic Valve Insufficiency / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D002216:Captopril / Q000494:pharmacology*; D004195:Disease Models, Animal; D004452:Echocardiography; D004734:Energy Metabolism / Q000187:drug effects*; D005109:Extracellular Matrix / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D049268:Positron-Emission Tomography; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D012720:Severity of Illness Index; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D005227:Fatty Acids; D002216:Captopril; D051057:Proto-Oncogene Proteins c-akt; D054774:G-Protein-Coupled Receptor Kinase 5; C517897:Grk5 protein, rat
keywords: aortic valve insufficiency; captopril; heart ventricles; hypertrophy; metabolism; volume overload