- Title
- Cardiomyocyte functional etiology in heart failure with preserved ejection fraction is distinctive - A new preclinical model
- Creator
- Curl, Claire; Danes, Vennetia; Bell, James; Raaijmakers, Antonia; Ip, Wendy; Chandramouli, Chanchal; Harding, Tristan; Porrello, Enzo; Erickson, Jeffrey; Charchar, Fadi; Kompa, Andrew; Edgley, Amanda; Crossman, David; Soeller, Christian; Mellor, Kimberley; Kalman, Jonathan; Harrap, Stephen; Delbridge, Lea
- Date
- 2018
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/167695
- Identifier
- vital:13680
- Identifier
-
https://doi.org/10.1161/jaha.117.007451
- Identifier
- ISBN:2047-9980
- Abstract
- Background--Among the growing numbers of patients with heart failure, up to one half have heart failure with preserved ejection fraction (HFpEF). The lack of effective treatments for HFpEF is a substantial and escalating unmet clinical need-and the lack of HFpEF-specific animal models represents a major preclinical barrier in advancing understanding of HFpEF. As established treatments for heart failure with reduced ejection fraction (HFrEF) have proven ineffective for HFpEF, the contention that the intrinsic cardiomyocyte phenotype is distinct in these 2 conditions requires consideration. Our goal was to validate and characterize a new rodent model of HFpEF, undertaking longitudinal investigations to delineate the associated cardiac and cardiomyocyte pathophysiology. Methods and Results--The selectively inbred Hypertrophic Heart Rat (HHR) strain exhibits adult cardiac enlargement (without hypertension) and premature death (40% mortality at 50 weeks) compared to its control strain, the normal heart rat. Hypertrophy was characterized in vivo by maintained systolic parameters (ejection fraction at 85%-90% control) with marked diastolic dysfunction (increased E/E'). Surprisingly, HHR cardiomyocytes were hypercontractile, exhibiting high Ca
- Publisher
- American Heart Association Inc.
- Relation
- Journal of the American Heart Association Vol. 7, no. 11 (2018), p. 1-32
- Rights
- http://creativecommons.org/licenses/by-nc-nd/4.0/
- Rights
- Copyright © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
- Rights
- Open Access
- Rights
- This metadata is freely available under a CCO license
- Subject
- 1102 Cardiorespiratory Medicine and Haematology; Calcium handling; Cardiac; Cardiomyocyte; Fibrosis; Heart failure preserved ejection fraction; Hypertrophy
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