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Effects of chronic neutral endopeptidase inhibition on the progression of left ventricular dysfunction and remodeling in dogs with moderate heart failure.
Cardiovasc Drugs Ther. 2002 May; 16(3):209-14.CD

Abstract

BACKGROUND

The diuretic actions of endogenously produced atrial natriuretic factor (ANF) may be beneficial in the treatment of chronic heart failure (CHF). Neutral endopeptidase (NEP) is the primary enzyme responsible for the degradation of ANF. The present study investigates the effects of long-term NEP inhibition on the progression of left ventricular (LV) dysfunction and remodeling in dogs with moderate heart failure.

METHODS

LV dysfunction was produced in 12 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LV ejection fraction (EF) was between 30-40%. Two weeks after the last embolization, dogs were randomized to 3 months of oral therapy with the NEP inhibitor ecadotril (100 mg, once daily, n = 6) or to no therapy at all (control, n = 6).

RESULTS

During the 3 months of follow-up, LV EF in control dogs decreased from 37 +/- 1% to 28 +/- 1% (P < 0.01) and LV end-diastolic volume (EDV) and end-systolic volume (ESV) increased (EDV: 72 +/- 3 vs. 84 +/- 5 ml, P < 0.01); ESV: 45 +/- 1 vs. 60 +/- 4 ml, P < 0.01). In dogs treated with ecadotril, LV EF (34 +/- 1% vs. 37 +/- 2%), EDV (79+/- 5 vs. 78+/- 6 ml) and ESV (52 +/- 3 vs. 49 +/- 4) remained essentially unchanged after 3 months of therapy. Histomorphometric measurements at the termination of the study showed that ecadotril was associated with significantly reduced cardiomyocyte hypertrophy compared to control.

CONCLUSION

Early, long-term NEP inhibition with ecadotril prevents the progression of LV dysfunction and attenuates progressive LV remodeling in dogs with moderate heart failure.

Authors+Show Affiliations

Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, 2799 W. Grand Boulevard, Detroit, MI 48202, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12374898

Citation

Mishima, Takayuki, et al. "Effects of Chronic Neutral Endopeptidase Inhibition On the Progression of Left Ventricular Dysfunction and Remodeling in Dogs With Moderate Heart Failure." Cardiovascular Drugs and Therapy, vol. 16, no. 3, 2002, pp. 209-14.
Mishima T, Tanimura M, Suzuki G, et al. Effects of chronic neutral endopeptidase inhibition on the progression of left ventricular dysfunction and remodeling in dogs with moderate heart failure. Cardiovasc Drugs Ther. 2002;16(3):209-14.
Mishima, T., Tanimura, M., Suzuki, G., Todor, A., Sharov, V. G., Tanhehco, E. J., Goldstein, S., & Sabbah, H. N. (2002). Effects of chronic neutral endopeptidase inhibition on the progression of left ventricular dysfunction and remodeling in dogs with moderate heart failure. Cardiovascular Drugs and Therapy, 16(3), 209-14.
Mishima T, et al. Effects of Chronic Neutral Endopeptidase Inhibition On the Progression of Left Ventricular Dysfunction and Remodeling in Dogs With Moderate Heart Failure. Cardiovasc Drugs Ther. 2002;16(3):209-14. PubMed PMID: 12374898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of chronic neutral endopeptidase inhibition on the progression of left ventricular dysfunction and remodeling in dogs with moderate heart failure. AU - Mishima,Takayuki, AU - Tanimura,Mitsuhiro, AU - Suzuki,George, AU - Todor,Anastassia, AU - Sharov,Victor G, AU - Tanhehco,Elaine J, AU - Goldstein,Sidney, AU - Sabbah,Hani N, PY - 2002/10/11/pubmed PY - 2003/7/15/medline PY - 2002/10/11/entrez SP - 209 EP - 14 JF - Cardiovascular drugs and therapy JO - Cardiovasc Drugs Ther VL - 16 IS - 3 N2 - BACKGROUND: The diuretic actions of endogenously produced atrial natriuretic factor (ANF) may be beneficial in the treatment of chronic heart failure (CHF). Neutral endopeptidase (NEP) is the primary enzyme responsible for the degradation of ANF. The present study investigates the effects of long-term NEP inhibition on the progression of left ventricular (LV) dysfunction and remodeling in dogs with moderate heart failure. METHODS: LV dysfunction was produced in 12 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LV ejection fraction (EF) was between 30-40%. Two weeks after the last embolization, dogs were randomized to 3 months of oral therapy with the NEP inhibitor ecadotril (100 mg, once daily, n = 6) or to no therapy at all (control, n = 6). RESULTS: During the 3 months of follow-up, LV EF in control dogs decreased from 37 +/- 1% to 28 +/- 1% (P < 0.01) and LV end-diastolic volume (EDV) and end-systolic volume (ESV) increased (EDV: 72 +/- 3 vs. 84 +/- 5 ml, P < 0.01); ESV: 45 +/- 1 vs. 60 +/- 4 ml, P < 0.01). In dogs treated with ecadotril, LV EF (34 +/- 1% vs. 37 +/- 2%), EDV (79+/- 5 vs. 78+/- 6 ml) and ESV (52 +/- 3 vs. 49 +/- 4) remained essentially unchanged after 3 months of therapy. Histomorphometric measurements at the termination of the study showed that ecadotril was associated with significantly reduced cardiomyocyte hypertrophy compared to control. CONCLUSION: Early, long-term NEP inhibition with ecadotril prevents the progression of LV dysfunction and attenuates progressive LV remodeling in dogs with moderate heart failure. SN - 0920-3206 UR - https://www.unboundmedicine.com/medline/citation/12374898/Effects_of_chronic_neutral_endopeptidase_inhibition_on_the_progression_of_left_ventricular_dysfunction_and_remodeling_in_dogs_with_moderate_heart_failure_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&amp;PAGE=linkout&amp;SEARCH=12374898.ui DB - PRIME DP - Unbound Medicine ER -