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(Circulation. 2006;114:1933-1939.)
© 2006 American Heart Association, Inc.

Heart Failure

Pretreatment With Angiotensin Receptor Blockade Prevents Left Ventricular Dysfunction and Blunts Left Ventricular Remodeling Associated With Acute Myocardial Infarction

Hoang Thai, MD; Lisa Castellano, DO; Elizabeth Juneman, MD; Huy Phan, PhD, MD; Rose Do, MD; Mohamed A. Gaballa, PhD; Steven Goldman, MD

From the Cardiology Section, Southern Arizona Veterans Affairs Health Care System Medical Center and Sarver Heart Center, University of Arizona, Tucson.

Correspondence to Hoang M. Thai, MD, Assistant Professor of Medicine, Cardiology Section, 1–111C, Southern Arizona VA Health Care System Hospital, 3601 S 6th Ave, Tucson, AZ 85723. E-mail hoang.thai{at}med.va.gov

Received July 21, 2006; revision received August 24, 2006; accepted August 25, 2006.

Background— This study was designed to determine the effects of pretreatment with an angiotensin receptor blocker on left ventricular (LV) function and remodeling during acute myocardial infarction (MI).

Methods and Results— Sprague-Dawley rats were pretreated with candesartan (10 mg · kg^–1 · d^–1) for 2 weeks and studied at 1, 3, and 6 minutes after MI. Compared with untreated rats, pretreatment with candesartan lowered (P<0.05) LV systolic pressure and the first derivative of LV pressure with respect to time but did not change LV end-diastolic pressure or improve LV regional function. With candesartan pretreatment, LV fractional shortening and ejection fraction increased (P<0.05) by 37% and 28%, and LV chamber dilation was attenuated (P<0.05). At 6 minutes after MI, LV endothelial nitric oxide synthase decreased in the infarcted and noninfarcted wall 47% (P=0.04) and 70% (P=0.002), and constitutive microtubulin increased 260% (P=0.0005) and 111% (P=0.003). Candesartan had no effect on LV tissue endothelial nitric oxide synthase levels but attenuated the increase in constitutive microtubulin by 77% (P=0.004) and 37% (P<0.05).

Conclusions— Pretreatment with candesartan before an acute MI improves global LV function, prevents LV dilation, and blunts the increase in constitutive microtubulin, with minimal effects on LV hemodynamics, regional function, or tissue endothelial nitric oxide synthase. Thus, candesartan given before an MI attenuates LV remodeling and alters the cytoskeleton matrix of the left ventricle.

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CLINICAL PERSPECTIVE

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