title: Effects of long-term monotherapy with metoprolol CR/XL on the progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure.
abstract: We examined the effects of long-term monotherapy with the beta-blocker, metoprolol controlled release/extended release (CR/XL), on the progression of LV dysfunction as well as on global and cellular remodeling in dogs with heart failure (HF). Chronic HF was produced by intracoronary microembolizations that were discontinued when LV ejection fraction (EF) was between 30% and 40%. Dogs were randomized to 3 months oral monotherapy with metoprolol CR/XL (100 mg once daily, n = 7) or no therapy at all (control, n = 7). In control dogs, EF decreased from 38 +/- 1% to 31 +/- 2% (p = 0.002), and LV end-systolic volume (ESV) and LV end-diastolic volume (EDV) increased (37 +/- 2 vs 45 +/- 2 ml, p = 0.001; 59 +/- 3 vs 65 +/- 3 ml, p = 0.001; respectively) during the 3 month follow-up period. In dogs treated with metoprolol CR/XL, EF increased after 3 months from 36 +/- 1% to 43 +/- 1% (p = 0.001), and ESV decreased (42 +/- 2 vs 38 +/- 2 ml, p = 0.003), whereas EDV remained unchanged. Compared to controls, treatment with metoprolol CR/XL showed 46% reduction in replacement fibrosis, 54% reduction in interstitial fibrosis and 20% reduction in myocyte cross-sectional area, a measure of myocyte hypertrophy. These findings indicate that metoprolol CR/XL improves LV function and attenuates progressive global and cellular LV remodeling in dogs with HF. The benefits are fully attributable to beta-blockade alone as no other adjunctive therapy was used.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, MI, USA.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Morita
authors.forename: George
authors.initials: G
authors.lastname: Suzuki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Mishima
authors.forename: Pervaiz A
authors.initials: PA
authors.lastname: Chaudhry
authors.forename: Petros V
authors.initials: PV
authors.lastname: Anagnostopoulos
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Tanhehco
authors.forename: Victor G
authors.initials: VG
authors.lastname: Sharov
authors.forename: Sidney
authors.initials: S
authors.lastname: Goldstein
authors.forename: Hani N
authors.initials: HN
authors.lastname: Sabbah
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D002908:Chronic Disease; D004285:Dogs; D005260:Female; D005355:Fibrosis; D006331:Heart Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D008297:Male; D008790:Metoprolol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000319:Adrenergic beta-Antagonists; D008790:Metoprolol