We compared the effects of heart rate reduction (HRR) by the 
hyperpolarization-activated pacemaker current (I(f)) channel inhibitor 
ivabradine (MI+Iva) and the beta(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)-beta1 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.