title: Effects of ivabradine and metoprolol on cardiac angiogenesis and endothelial dysfunction in rats with heart failure.
abstract: Myocardial infarction (MI)-induced remodeling is associated with disturbed myocardial perfusion through vascular changes, such as reduced capillary density and endothelial dysfunction. Heart rate reduction (HRR) initiated immediately after MI stimulates angiogenesis and attenuates left ventricular dysfunction. We aimed to investigate the effects of long-term HRR on cardiac angiogenesis and endothelial function in a rat model of post-MI heart failure. Rats received early or late ivabradine or metoprolol for 12 or 9 weeks, respectively, and compared with untreated MI and sham animals 12 weeks after MI. Heart rate was measured in the conscious rat. MI resulted in an increased heart weight to body weight ratio, a decline in capillary density and a marked reduction in acetylcholine-induced relaxation. Early and late HRR by either ivabradine or metoprolol significantly increased capillary to myocyte ratio. Moreover, this ratio was significantly correlated to heart rate (r = -0.324 and P = 0.036). Neither early nor late chronic HRR prevented endothelial dysfunction, except a moderate improvement in late MI ivabradine group. In MI rats, HRR either by ivabradine or metoprolol treatment increases cardiac angiogenesis. Late HRR strategy was comparable to early HRR, suggesting that the beneficial effects are independent of the time of onset of therapy after MI.
authors.affiliation: Departments of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. n.ulu@med.umcg.nl
authors.forename: Nadir
authors.initials: N
authors.lastname: Ulu
authors.forename: Rob H
authors.initials: RH
authors.lastname: Henning
authors.forename: Maaike
authors.initials: M
authors.lastname: Goris
authors.forename: Regien G
authors.initials: RG
authors.lastname: Schoemaker
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
mesh_terms: D000818:Animals; D001552:Benzazepines; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D000077550:Ivabradine; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000150:complications
chemical_list: D001552:Benzazepines; D000077550:Ivabradine; D008790:Metoprolol