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This Article Full Text Full Text (PDF) All Versions of this Article: 01337.2008v2    most recent 297/1/H322 01337.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Christensen, L. P. Articles by Tomanek, R. J. PubMed PubMed Citation Articles by Christensen, L. P. Articles by Tomanek, R. J.

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

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 β₁-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 (AT₁) 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