Postmyocardial infarction remodeling and coronary reserve: effects of ivabradine and beta blockade therapy

• Published in: American journal of physiology. Heart and circulatory physiology 2009-07, Vol.297 (1), p.H322-H330
• Main Authors: Christensen, Lance P, Zhang, Ron-ling, Zheng, Wei, Campanelli, Joseph J, Dedkov, Eduard I, Weiss, Robert M, Tomanek, Robert J
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - therapeutic use; Angiotensin II - biosynthesis; Angiotensin II - physiology; Animals; Atenolol - therapeutic use; Benzazepines - therapeutic use; Beta blockers; Bradykinin - metabolism; Cardiotonic Agents - therapeutic use; Collagen - metabolism; Coronary Circulation - drug effects; Coronary vessels; Drug therapy; Electrocardiography; Heart attacks; Heart rate; Heart Rate - drug effects; Immunohistochemistry; Intercellular Signaling Peptides and Proteins - metabolism; Male; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Organ Size; Perfusion; Physiology; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1 - biosynthesis; Receptor, Angiotensin, Type 1 - physiology; Rodents; Ventricular Remodeling - physiology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01337.2008

Department of Anatomy and Cell Biology, Department of Internal Medicine, and Cardiovascular Center, University of Iowa, Iowa City, Iowa Submitted 29 December 2008 ; accepted in final form 23 April 2009 We compared the effects of heart rate reduction (HRR) by the hyperpolarization-activated pacemaker current ( I f ) channel inhibitor ivabradine (MI+Iva) and the β 1 -blocker atenolol (MI+Aten) on ventricular remodeling and perfusion after myocardial infarction (MI) in middle-aged (12 mo) Sprague-Dawley rats. Mean HRR was virtually identical in the two treated groups (19%). Four weeks after coronary artery ligation, maximal myocardial perfusion fell in the MI group but was preserved in infarcted rats treated with either Iva or Aten. However, coronary reserve in the remodeled hearts was preserved only with Iva, since Aten treatment elevated baseline perfusion in response to a higher wall stress. The higher maximal perfusion noted in the two treated groups was not due to arteriogenesis or angiogenesis. Plasma levels of angiotensin (ANG) II and myocardial ANG type 1 (AT 1 ) receptor and transforming growth factor (TGF)-β1 were reduced during the first week of treatment by both Iva and Aten. Moreover, treatment also reduced arteriolar perivascular collagen density. Despite these similar effects of Iva and Aten on vascularity and ANG II, Iva, but not Aten, attenuated the decline in ejection fraction and lowered left ventricular (LV) end-diastolic volume (LVEDV)-to-LV mass ratio, determined by echocardiography. In conclusion, 1 ) Iva has advantages over Aten in postinfarction therapy that are not due to differential effects of the drugs on heart rate, and 2 ) age limits growth factor upregulation, angiogenesis, and arteriogenesis in the postinfarcted heart. arterioles; capillaries; ejection fraction; growth factors; angiotensin II Address for reprint requests and other correspondence: R. J. Tomanek, Dept. of Anatomy and Cell Biology, 1-402 BSB, Univ. of Iowa, Iowa City, IA 52242 (e-mail: robert-tomanek{at}iowa.edu )