title: Usefulness of carvedilol in the treatment of chronic aortic valve regurgitation.
abstract: BACKGROUND
  Aortic regurgitation (AR) is a chronic disease for which there is currently no approved medical treatment. We previously reported in an animal model that β-blockade with metoprolol exerted beneficial effects on left ventricular remodeling and survival. Despite the recent publication of promising human data, β-blockade in chronic AR remains controversial. More data are needed to support this potentially new treatment strategy. We hypothesized that carvedilol might be another safe treatment option in chronic AR, considering its combined β-blocking and α-blocking effects and proven efficacy in patients with established heart failure.
  
  
  RESULTS
  The effects of a 6-month treatment with carvedilol 30 mg/kg/d orally were evaluated in adult Wistar rats with severe AR. Sham-operated and untreated AR animals were used as controls. Carvedilol treatment resulted in less left ventricular hypertrophy and dilatation. Ejection fraction was improved and filling pressures were reduced by carvedilol. β1-Receptor expression was also improved as well as myocardial capillary density. Those beneficial effects were noted despite the presence of drug-induced bradycardia.
  
  
  CONCLUSIONS
  Carvedilol exerted protective effects against volume-overload cardiomyopathy in this model of aortic valve regurgitation with preserved ejection fraction. These results suggest a protective class effect of β-blockers. Combined with the recent publication of promising human data, our findings support the need to carefully design a prospective study in humans to evaluate the effects of β-blockers in chronic aortic valve regurgitation.
authors.affiliation: Groupe de Recherche sur les Valvulopathies, Centre de Recherche de l'Institut universitaire de Cardiologie et pneumologie de Québec, Université Laval, Quebec, Canada.
authors.forename: Adnane
authors.initials: A
authors.lastname: Zendaoui
authors.forename: Dominic
authors.initials: D
authors.lastname: Lachance
authors.forename: Elise
authors.initials: E
authors.lastname: Roussel
authors.forename: Jacques
authors.initials: J
authors.lastname: Couet
authors.forename: Marie
authors.initials: M
authors.lastname: Arsenault
mesh_terms: D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001022:Aortic Valve Insufficiency / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001919:Bradycardia / Q000139:chemically induced; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D002227:Carbazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000077261:Carvedilol; D002908:Chronic Disease; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics; D038702:Follistatin-Related Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006339:Heart Rate / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000517:prevention & control; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D011412:Propanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000235:genetics; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D016326:Extracellular Matrix Proteins; D038702:Follistatin-Related Proteins; D011412:Propanolamines; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain; C448719:Fstl1 protein, rat; D009320:Atrial Natriuretic Factor