Tags

Type your tag names separated by a space and hit enter

Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure.
Circulation. 2002 Dec 03; 106(23):2967-72.Circ

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart & Vascular Institute, Detroit, Mich, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12460880

Citation

Suzuki, George, et al. "Effects of Long-term Monotherapy With Eplerenone, a Novel Aldosterone Blocker, On Progression of Left Ventricular Dysfunction and Remodeling in Dogs With Heart Failure." Circulation, vol. 106, no. 23, 2002, pp. 2967-72.
Suzuki G, Morita H, Mishima T, et al. Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. Circulation. 2002;106(23):2967-72.
Suzuki, G., Morita, H., Mishima, T., Sharov, V. G., Todor, A., Tanhehco, E. J., Rudolph, A. E., McMahon, E. G., Goldstein, S., & Sabbah, H. N. (2002). Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. Circulation, 106(23), 2967-72.
Suzuki G, et al. Effects of Long-term Monotherapy With Eplerenone, a Novel Aldosterone Blocker, On Progression of Left Ventricular Dysfunction and Remodeling in Dogs With Heart Failure. Circulation. 2002 Dec 3;106(23):2967-72. PubMed PMID: 12460880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. AU - Suzuki,George, AU - Morita,Hideaki, AU - Mishima,Takayuki, AU - Sharov,Victor G, AU - Todor,Anastassia, AU - Tanhehco,Elaine J, AU - Rudolph,Amy E, AU - McMahon,Ellen G, AU - Goldstein,Sidney, AU - Sabbah,Hani N, PY - 2002/12/4/pubmed PY - 2002/12/21/medline PY - 2002/12/4/entrez SP - 2967 EP - 72 JF - Circulation JO - Circulation VL - 106 IS - 23 N2 - 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. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/12460880/Effects_of_long_term_monotherapy_with_eplerenone_a_novel_aldosterone_blocker_on_progression_of_left_ventricular_dysfunction_and_remodeling_in_dogs_with_heart_failure_ L2 - http://www.ahajournals.org/doi/full/10.1161/01.cir.0000039104.56479.42?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -