title: Effect of Chronic Heart Rate Reduction by I(f) Current Inhibitor Ivabradine on Left Ventricular Remodeling and Systolic Performance in Middle-Aged Rats With Postmyocardial Infarction Heart Failure.
abstract: BACKGROUND
  A large myocardial infarction (MI) initiates progressive cardiac remodeling that leads to systolic heart failure (HF). Long-term heart rate reduction (HRR) induced by the I f current inhibitor ivabradine (IVA) ameliorates left ventricular (LV) remodeling and improves systolic performance in young post-MI rats. However, the beneficial effects of chronic IVA treatment in middle-aged rats remain to be determined.
  
  
  METHODS
  A large MI was induced in 12-month-old rats by left coronary artery ligation. Rats were treated with IVA via osmotic pumps intraperitoneal in a dose of 10.5 mg/kg/d (MI + IVA) and compared with MI and sham-operated animals 12 weeks after MI.
  
  
  RESULTS
  Heart rate in MI + IVA rats was on average 29% lower than that of rats in the MI group. Left ventricular remodeling was comparable between post-MI groups, although MI + IVA rats did not show the compensatory thickening of the noninfarcted myocardium. Chronic HRR had no effect on transverse cardiac myocyte size and capillary growth, but it reduced the collagen content in noninfarcted myocardium. Left ventricular systolic performance remained similarly impaired in MI and MI + IVA rats. Moreover, abrupt IVA withdrawal led to worsening HF and reduction of coronary reserve.
  
  
  CONCLUSIONS
  Our data reveal that chronic IVA-induced HRR does not provide sustainable benefits for LV systolic performance in middle-aged rats with post-MI HF.
authors.affiliation: Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA ededkov@nyit.edu.
authors.forename: Eduard I
authors.initials: EI
authors.lastname: Dedkov
authors.affiliation: Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA.
authors.forename: Yevgen
authors.initials: Y
authors.lastname: Bogatyryov
authors.affiliation: Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA.
authors.forename: Daniela Scaldaferri
authors.initials: DS
authors.lastname: McCooey
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Lance P
authors.initials: LP
authors.lastname: Christensen
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Weiss
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tomanek
mesh_terms: D000375:Aging; D000818:Animals; D001552:Benzazepines / Q000627:therapeutic use*; D003094:Collagen / Q000032:analysis; D003331:Coronary Vessels / Q000187:drug effects; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors*; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D000077550:Ivabradine; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013599:Systole / Q000187:drug effects*; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D001552:Benzazepines; D054815:Cyclic Nucleotide-Gated Cation Channels; D000077550:Ivabradine; D003094:Collagen
keywords: cardiac remodeling; heart failure; heart rate reduction; ivabradine; myocardial infarction