title: Preservation of coronary reserve by ivabradine-induced reduction in heart rate in infarcted rats is associated with decrease in perivascular collagen.
abstract: We tested the hypothesis that chronically reducing the heart rate in infarcted middle-aged rats using ivabradine (IVA) would induce arteriolar growth and attenuate perivascular collagen and, thereby, improve maximal perfusion and coronary reserve in the surviving myocardium. Myocardial infarction (MI) was induced in 12-mo-old male Sprague-Dawley rats, which were then treated with either IVA (10.5 mg.kg(-1).day(-1); MI + IVA) or placebo (MI) via intraperitoneal osmotic pumps for 4 wk. Four weeks of IVA treatment limited the increase in left ventricular end-diastolic pressure and the decrease in ejection fraction but did not affect the size of the infarct, the magnitude of myocyte hypertrophy, or the degree of arteriolar and capillary growth. However, treatment reduced interstitial and periarteriolar collagen in the surviving myocardium of MI + IVA rats. The reduced periarteriolar collagen content was associated with improvement in maximal myocardial perfusion and coronary reserve. Although the rates of proliferation of periarteriolar fibroblasts were similar in the MI and MI + IVA groups, the expression levels of the AT(1) receptor and transforming growth factor (TGF)-beta(1) in the myocardium, as well as the plasma level of the ANG II peptide, were lower in treated rats 14 days after MI. Therefore, our data reveal that improved maximal myocardial perfusion and coronary reserve in MI + IVA rats are most likely the result of reduced periarteriolar collagen rather than enhanced arteriolar growth.
authors: Department of Biomedical Sciences, New York College of Osteopathic Medicine/NYIT, Old Westbury, NY 11568, USA. ededkov@nyit.edu
authors: Eduard I
authors: EI
authors: Dedkov
authors: Wei
authors: W
authors: Zheng
authors: Lance P
authors: LP
authors: Christensen
authors: Robert M
authors: RM
authors: Weiss
authors: Florence
authors: F
authors: Mahlberg-Gaudin
authors: Robert J
authors: RJ
authors: Tomanek
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage*; D003094:Collagen / Q000378:metabolism*; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D053805:Fractional Flow Reserve, Myocardial / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D000077550:Ivabradine; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001552:Benzazepines; D000077550:Ivabradine; D003094:Collagen