Unmasking of estrogen dependent changes in left ventricular structure‐function in aged female rats: A potential model for pre‐HFpEF

Key points

Heart failure with preserved ejection fraction (HFpEF) is seen more frequently in older women and risk factors include age, hypertension and excess weight No female animal models of early stage remodelling (pre‐HFpEF) have examined the effects that the convergence of such factors have on cardiac structure and function In this study, we demonstrate that aging can lead to the development of mild chamber remodelling, diffuse fibrosis and loss of diastolic function The loss of estrogens further aggravates such changes by leading to a notable drop in cardiac output (while preserving normal ejection fraction) in the presence of diffuse fibrosis that is more predominant in endocardium and is accompanied by papillary fibrosis Excess weight did not markedly aggravate such findings This animal model recapitulates many of the features recognized in older, female HFpEF patients and thus, may serve to examine the effects of candidate therapeutic agents

Abstract

Two‐thirds of patients with heart failure with preserved ejection fraction (HFpEF) are older women and risk factors include hypertension and excess weight/obesity. Pathophysiological factors that drive early disease development (before heart failure ensues) remain obscure and female animal models are lacking. The study evaluated the intersecting roles of aging, estrogen depletion and excess weight on altering cardiac structure/function. Female, 18 month old, Fischer F344 rats were divided into aging group, aging + ovariectomy (OVX) and aging + ovariectomy plus 10% fructose (OVF) in drinking water (n = 8‐16/group) to induce weight gain. Left ventricular (LV) structure/function was monitored by echocardiography. At 22 months of age, animals were anaesthetized and catheter‐based hemodynamics evaluated, followed by histological measures of chamber morphometry and collagen density. All aged animals developed hypertension. OVF animals increased body weight. Echocardiography only detected mild chamber remodelling with aging while intraventricular pressure‐volume loop analysis showed significant (P < 0.05) decreases vs. aging in stroke volume (13% OVX and 15% for OVF), stroke work (34% and 52%), cardiac output (29% and 27%), and increases in relaxation time (10% OVX) with preserved ejection fraction. Histology indicated papillary and interstitial fibrosis with aging, which was higher in the endocardium of OVX and OVF groups. With aging, ovariectomy leads to the loss of diastolic and global LV function while preserving ejection fraction. This model recapitulates many cardiovascular features present in HFpEF patients and may help understand the roles that aging and estrogen depletion play in early (pre‐HFpEF) disease development.

This article is protected by copyright. All rights reserved

from Physiology via xlomafota13 on Inoreader http://bit.ly/2ScARoQ
via IFTTT