Effects of Long-Term Monotherapy With Eplerenone, a Novel Aldosterone Blocker, on Progression of Left Ventricular Dysfunction and Remodeling in Dogs With Heart Failure.
Suzuki, George MD; Morita, Hideaki MD; Mishima, Takayuki MD; Sharov, Victor G. MD, PhD; Todor, Anastassia MD; Tanhehco, Elaine J. PhD; Rudolph, Amy E. PhD; McMahon, Ellen G. PhD; Goldstein, Sidney MD; Sabbah, Hani N. PhD
106(23):2967-2972, December 3, 2002.
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Background-: In heart failure (HF), aldosterone has been implicated in the formation of reactive interstitial fibrosis, a maladaptation that contributes to left ventricular (LV) remodeling. Eplerenone is a novel selective aldosterone blocker. The present study examined the effects of long-term monotherapy with eplerenone on the progression of LV dysfunction and remodeling in dogs with chronic HF.
Methods and Results-: HF was produced in 14 dogs by intracoronary microembolizations that were discontinued when LV ejection fraction (EF) was between 30% and 40%. Two weeks after the last embolization, dogs were randomized to 3 months of oral therapy with eplerenone (10 mg/kg twice daily, n=7) or no therapy at all (control, n=7). Hemodynamic measurements were made just before randomization and were repeated at the end of 3 months of therapy. In control dogs, LV end-diastolic and end-systolic volume increased significantly (62 /-4 versus 68 /-4 mL, P <0.001, and 38 /-3 versus 47 /-3 mL, P <0.001, respectively), and EF decreased significantly (38 /-1% versus 31 /-2%, P <0.001). In contrast, end-diastolic volume, end-systolic volume, and EF remained unchanged during the 3 months of treatment in eplerenone-treated dogs. LV end-diastolic wall stress increased significantly in control dogs but decreased significantly in eplerenone-treated dogs. Compared with control, eplerenone was associated with a 28% reduction in cardiomyocyte cross-sectional area, a 37% reduction of volume fraction of reactive interstitial fibrosis, and a 34% reduction of volume fraction of replacement fibrosis.
Conclusions-: Our results indicate that long-term therapy with eplerenone prevents progressive LV dysfunction and attenuates LV remodeling in dogs with chronic HF.
(C) 2002 American Heart Association, Inc.