Tags

Type your tag names separated by a space and hit enter

Effects of long-term therapy with bosentan on the progression of left ventricular dysfunction and remodeling in dogs with heart failure.
J Am Coll Cardiol. 2000 Jan; 35(1):222-9.JACC

Abstract

OBJECTIVES

In this study, we examined the effects of long-term therapy with bosentan on the progression of LV dysfunction and remodeling in dogs with moderate HF.

BACKGROUND

Acute intravenous administration of bosentan, a mixed endothelin-1 type A and type B receptor antagonist, was shown to improve left ventricular (LV) function in patients and dogs with heart failure (HF).

METHODS

Left ventricular dysfunction was induced by multiple, sequential intracoronary microembolizations in 14 dogs. Embolizations were discontinued when LV ejection fraction (EF) was between 30% and 40%. Dogs were randomized to three months of therapy with bosentan (30 mg/kg twice daily, n = 7) or no therapy at all (control, n = 7).

RESULTS

In untreated dogs, EF decreased from 35 +/- 1% before initiating therapy to 29 +/- 1% at the end of three months of therapy (p = 0.001), and LV end-diastolic volume (EDV) and end-systolic volume (ESV) increased (EDV: 71 +/- 3 vs. 84 +/- 8 ml, p = 0.08; ESV: 46 +/- 2 vs. 60 +/- 6 ml, p = 0.03). By contrast, in dogs treated with bosentan, EF tended to increase from 34 +/- 2% before initiating therapy to 39 +/- 1% at the end of three months of therapy (p = 0.06), and EDV and ESV decreased (EDV: 75 +/- 3 vs. 71 +/- 4 ml, p = 0.05; ESV: 48 +/- 2 vs. 43 +/- 3 ml, p = 0.01). Furthermore, compared with untreated dogs, dogs treated with bosentan showed significantly less LV cardiomyocyte hypertrophy and LV volume fraction of interstitial fibrosis.

CONCLUSIONS

In dogs with moderate HF, long-term therapy with bosentan prevents the progression of LV dysfunction and attenuates LV chamber remodeling. The findings support the use of mixed endothelin-1 receptor antagonists as adjuncts to the long-term treatment of HF.

Authors+Show Affiliations

Department of Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan, USA.No 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

10636284

Citation

Mishima, T, et al. "Effects of Long-term Therapy With Bosentan On the Progression of Left Ventricular Dysfunction and Remodeling in Dogs With Heart Failure." Journal of the American College of Cardiology, vol. 35, no. 1, 2000, pp. 222-9.
Mishima T, Tanimura M, Suzuki G, et al. Effects of long-term therapy with bosentan on the progression of left ventricular dysfunction and remodeling in dogs with heart failure. J Am Coll Cardiol. 2000;35(1):222-9.
Mishima, T., Tanimura, M., Suzuki, G., Todor, A., Sharov, V. G., Goldstein, S., & Sabbah, H. N. (2000). Effects of long-term therapy with bosentan on the progression of left ventricular dysfunction and remodeling in dogs with heart failure. Journal of the American College of Cardiology, 35(1), 222-9.
Mishima T, et al. Effects of Long-term Therapy With Bosentan On the Progression of Left Ventricular Dysfunction and Remodeling in Dogs With Heart Failure. J Am Coll Cardiol. 2000;35(1):222-9. PubMed PMID: 10636284.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of long-term therapy with bosentan on the progression of left ventricular dysfunction and remodeling in dogs with heart failure. AU - Mishima,T, AU - Tanimura,M, AU - Suzuki,G, AU - Todor,A, AU - Sharov,V G, AU - Goldstein,S, AU - Sabbah,H N, PY - 2000/1/15/pubmed PY - 2000/1/15/medline PY - 2000/1/15/entrez SP - 222 EP - 9 JF - Journal of the American College of Cardiology JO - J. Am. Coll. Cardiol. VL - 35 IS - 1 N2 - OBJECTIVES: In this study, we examined the effects of long-term therapy with bosentan on the progression of LV dysfunction and remodeling in dogs with moderate HF. BACKGROUND: Acute intravenous administration of bosentan, a mixed endothelin-1 type A and type B receptor antagonist, was shown to improve left ventricular (LV) function in patients and dogs with heart failure (HF). METHODS: Left ventricular dysfunction was induced by multiple, sequential intracoronary microembolizations in 14 dogs. Embolizations were discontinued when LV ejection fraction (EF) was between 30% and 40%. Dogs were randomized to three months of therapy with bosentan (30 mg/kg twice daily, n = 7) or no therapy at all (control, n = 7). RESULTS: In untreated dogs, EF decreased from 35 +/- 1% before initiating therapy to 29 +/- 1% at the end of three months of therapy (p = 0.001), and LV end-diastolic volume (EDV) and end-systolic volume (ESV) increased (EDV: 71 +/- 3 vs. 84 +/- 8 ml, p = 0.08; ESV: 46 +/- 2 vs. 60 +/- 6 ml, p = 0.03). By contrast, in dogs treated with bosentan, EF tended to increase from 34 +/- 2% before initiating therapy to 39 +/- 1% at the end of three months of therapy (p = 0.06), and EDV and ESV decreased (EDV: 75 +/- 3 vs. 71 +/- 4 ml, p = 0.05; ESV: 48 +/- 2 vs. 43 +/- 3 ml, p = 0.01). Furthermore, compared with untreated dogs, dogs treated with bosentan showed significantly less LV cardiomyocyte hypertrophy and LV volume fraction of interstitial fibrosis. CONCLUSIONS: In dogs with moderate HF, long-term therapy with bosentan prevents the progression of LV dysfunction and attenuates LV chamber remodeling. The findings support the use of mixed endothelin-1 receptor antagonists as adjuncts to the long-term treatment of HF. SN - 0735-1097 UR - https://www.unboundmedicine.com/medline/citation/10636284/Effects_of_long_term_therapy_with_bosentan_on_the_progression_of_left_ventricular_dysfunction_and_remodeling_in_dogs_with_heart_failure_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735-1097(99)00528-8 DB - PRIME DP - Unbound Medicine ER -