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Load-Dependent Changes in Left Ventricular Structure and Function in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure.
Circ Heart Fail 2018; 11(5):e004351CH

Abstract

BACKGROUND

To better understand reverse left ventricular (LV) remodeling, we developed a murine model wherein mice develop LV remodeling after transverse aortic constriction (TAC) and a small apical myocardial infarct (MI) and undergo reverse LV remodeling after removal of the aortic band.

METHODS AND RESULTS

Mice studied were subjected to sham (n=6) surgery or TAC+MI (n=12). Two weeks post-TAC+MI, 1 group underwent debanding (referred to as heart failure debanding [HF-DB] mice; n=6), whereas the aortic band remained in a second group (heart failure [HF] group; n=6). LV remodeling was evaluated by 2D echocardiography at 1 day, 2 weeks and 6 weeks post-TAC+MI. The hearts were analyzed by transcriptional profiling at 4 and 6 weeks and histologically at 6 weeks. Debanding normalized LV volumes, LV mass, and cardiac myocyte hypertrophy at 6 weeks in HF-DB mice, with no difference in myofibrillar collagen in the HF and HF-DB mice. LV ejection fraction and radial strain improved after debanding; however, both remained decreased in the HF-DB mice relative to sham and were not different from HF mice at 6 weeks. Hemodynamic unloading in the HF-DB mice was accompanied by a 35% normalization of the HF genes at 2 weeks and 80% of the HF genes at 4 weeks.

CONCLUSIONS

Hemodynamic unloading of a pathophysiologically relevant mouse model of HF results in normalization of LV structure, incomplete recovery of LV function, and incomplete reversal of the HF transcriptional program. The HF-DB mouse model may provide novel insights into mechanisms of reverse LV remodeling.

Authors+Show Affiliations

Center for Cardiovascular Research, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO.Center for Cardiovascular Research, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO.Center for Cardiovascular Research, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO.Center for Cardiovascular Research, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO.Center for Cardiovascular Research, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO.Center for Cardiovascular Research, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO. dmann@wustl.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29716898

Citation

Weinheimer, Carla J., et al. "Load-Dependent Changes in Left Ventricular Structure and Function in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure." Circulation. Heart Failure, vol. 11, no. 5, 2018, pp. e004351.
Weinheimer CJ, Kovacs A, Evans S, et al. Load-Dependent Changes in Left Ventricular Structure and Function in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure. Circ Heart Fail. 2018;11(5):e004351.
Weinheimer, C. J., Kovacs, A., Evans, S., Matkovich, S. J., Barger, P. M., & Mann, D. L. (2018). Load-Dependent Changes in Left Ventricular Structure and Function in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure. Circulation. Heart Failure, 11(5), pp. e004351. doi:10.1161/CIRCHEARTFAILURE.117.004351.
Weinheimer CJ, et al. Load-Dependent Changes in Left Ventricular Structure and Function in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure. Circ Heart Fail. 2018;11(5):e004351. PubMed PMID: 29716898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Load-Dependent Changes in Left Ventricular Structure and Function in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure. AU - Weinheimer,Carla J, AU - Kovacs,Attila, AU - Evans,Sarah, AU - Matkovich,Scot J, AU - Barger,Philip M, AU - Mann,Douglas L, PY - 2017/06/23/received PY - 2018/03/22/accepted PY - 2018/5/3/entrez PY - 2018/5/3/pubmed PY - 2019/7/10/medline KW - echocardiography KW - gene expression KW - heart failure KW - left ventricular remodeling SP - e004351 EP - e004351 JF - Circulation. Heart failure JO - Circ Heart Fail VL - 11 IS - 5 N2 - BACKGROUND: To better understand reverse left ventricular (LV) remodeling, we developed a murine model wherein mice develop LV remodeling after transverse aortic constriction (TAC) and a small apical myocardial infarct (MI) and undergo reverse LV remodeling after removal of the aortic band. METHODS AND RESULTS: Mice studied were subjected to sham (n=6) surgery or TAC+MI (n=12). Two weeks post-TAC+MI, 1 group underwent debanding (referred to as heart failure debanding [HF-DB] mice; n=6), whereas the aortic band remained in a second group (heart failure [HF] group; n=6). LV remodeling was evaluated by 2D echocardiography at 1 day, 2 weeks and 6 weeks post-TAC+MI. The hearts were analyzed by transcriptional profiling at 4 and 6 weeks and histologically at 6 weeks. Debanding normalized LV volumes, LV mass, and cardiac myocyte hypertrophy at 6 weeks in HF-DB mice, with no difference in myofibrillar collagen in the HF and HF-DB mice. LV ejection fraction and radial strain improved after debanding; however, both remained decreased in the HF-DB mice relative to sham and were not different from HF mice at 6 weeks. Hemodynamic unloading in the HF-DB mice was accompanied by a 35% normalization of the HF genes at 2 weeks and 80% of the HF genes at 4 weeks. CONCLUSIONS: Hemodynamic unloading of a pathophysiologically relevant mouse model of HF results in normalization of LV structure, incomplete recovery of LV function, and incomplete reversal of the HF transcriptional program. The HF-DB mouse model may provide novel insights into mechanisms of reverse LV remodeling. SN - 1941-3297 UR - https://www.unboundmedicine.com/medline/citation/29716898/Load-Dependent_Changes_in_Left_Ventricular_Structure_and_Function_in_a_Pathophysiologically_Relevant_Murine_Model_of_Reversible_Heart_Failure L2 - http://www.ahajournals.org/doi/full/10.1161/CIRCHEARTFAILURE.117.004351?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -