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Functional and Bioenergetic Consequences of AT1 Antagonist Olmesartan Medoxomil in Hearts With Postinfarction LV Remodeling

Ochiai, Koichi MD, PhD; Hu, Qingsong MD, MS; Lee, Joseph BS; Mansoor, Abdul MD, PhD; Liu, Jingbo MD, PhD; Wang, Xiaohong MD, PhD; Gong, Guangrong MD, MS; Murakami, Yo MD, PhD; Ishibashi, Yukada MD, PhD; Shimada, Toshio MD, PhD; Zhang, Jianyi MD, PhD

Journal of Cardiovascular Pharmacology:
doi: 10.1097/01.fjc.0000211760.29141.c1
Original Articles
Abstract

The structural left ventricular (LV) remodeling and contractile dysfunction of hearts with postinfarction LV remodeling are benefited by angiotensin II type 1 receptor (AT1) blocker. However, the myocardial bioenergetic consequences of AT1 blocker in these hearts are not known. To investigate, we used a porcine model of postinfarction LV remodeling produced by ligation of the left circumflex coronary artery. After infarction, 7 pigs received olmesartan medoxomil (2 mg/kg) for comparison against 9 untreated and 10 normal pigs. Measurements of hemodynamics, myocardial perfusion, and myocardial bioenergetics were taken 7 weeks postinfarction. The treated group had an LV-to-body weight ratio significantly lower than the untreated group (2.69±0.70, 2.96±0.51, 3.66±0.60 g/kg for control, treated, and untreated groups, respectively). The untreated group had a mean aortic pressure significantly higher than the control (73±16, 86±14, and 94±20 mm Hg, respectively). The subendocardial phosphocreatine-to-ATP ratios of the treated group were significantly higher than that of the untreated group. The untreated group, but not the treated group, had significant reductions in mitochondrial F0F1-ATPase subunits compared with controls. Congestive heart failure as evidenced by significant ascites (100 to 2000 mL) developed in 4 of the 9 untreated animals, but was absent in the treated group. Animals with heart failure demonstrated reductions in both mitochondrial F0F1-ATPase expression and myocardial high-energy phosphate levels. Thus, severe LV dysfunction and accompanying abnormal myocardial bioenergetic phenotype were prevented by the AT1 antagonist olmesartan medoxomil.

Author Information

Departments of Medicine and Radiology, University of Minnesota Health Sciences, Minneapolis, MN 55455

Supported by US Public Health Service Grants HL50470, HL61353, HL67828, and HL71970.

Reprints: Jianyi Zhang, MD, PhD, University of Minnesota Academic Health Center, Mayo Mail Code 508, 420 Delaware Street SE, Minneapolis, MN 55455 (e-mail: zhang047@umn.edu)

Received for publication December 14, 2005; accepted March 15, 2006

The current address for Koichi Ochiai, Yo Murakami, and Toshio Shimada is Department of Cardiology, Shimane University School of Medicine, Izumo, Shimane 693–8501, Japan.

The authors Koichi Ochiai, Qingsong Hu, and Joseph Lee contributed equally to this manuscript.

© 2006 Lippincott Williams & Wilkins, Inc.