Submitted on December 29, 2008
Revised on April 14, 2009
Accepted on April 23, 2009
Post Myocardial Infarction Remodeling and Coronary Reserve: Effects of Invabradine and Beta Blockade Therapy
Lance P Christensen1, Ron-ling Zhang1, Wei Zheng1, Joseph J Campanelli1, Eduard I. Dedkov1, Robert M. Weiss2, and Robert J. Tomanek1*
1 University of Iowa
2 Univ. Iowa
* To whom correspondence should be addressed. E-mail: robert-tomanek{at}uiowa.edu.
We compared the effects of heart rate reduction (HRR) by the If channel inhibitor, ivabradine (MI+IVA) and the 
1-blocker, atenolol (MI+ATEN) on ventricular remodeling and perfusion after myocardial infarction (MI) in middle-aged (12 mo) Sprague-Dawley rats. Mean heart rate reduction (HRR) was virtually identical in the 2 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 ivabradine or atenolol. However, coronary reserve was preserved only with ivabradine, since atenolol treatment elevated baseline perfusion in response to higher wall stress. The higher maximal perfusion noted in the two treated groups was not due to arteriogenesis or angiogenesis. Plasma levels of angiotensin II (Ang II) and myocardial AT1 receptor and TGF- 1 were reduced during the first week of treatment by both ivabradine and atenolol. Moreover, treatment also reduced arteriolar perivascular collagen density. Despite these similar effects of ivabradine and atenolol on vascularity and Ang II, ivabradine, but not atenolol, attenuated the decline in ejection fraction and lowered LVEDV/LV mass ratio, determined by echocardiography. In conclusion: 1) ivabradine has advantages over atenolol in post-infarction therapy that are not due to differential effects of the drugs on heart rate; 2) age limits, growth factor, up-regulation, angiogenesis and arteriogenesis in the post-infarcted heart.
