Age-associated alterations of cardiac structure and function in the female F344xBN rat heart

Abstract

The Fischer 344/NNiaHSD × Brown Norway/BiNia F1 (F344xBN) rat model exhibits an increased life span and fewer age-associated pathologies compared to commonly used Fischer 344 (F344). How aging may affect cardiac structure and function in these animals, has to our knowledge, not been investigated. Echocardiography was performed on female F344xBN rats at 6, 26, and 30 months of age using a Phillips 5500 Echocardiography system. Before sacrifice, electrocardiograms were measured in the female F344xBN in order to determine heart rhythm interval changes. Aging was associated with an increase in heart to body weight ratio, cardiomyocyte cross-sectional area, posterior wall thickening, and left ventricle chamber dilatation. Aging was associated with slight evidence of diastolic dysfunction. Alterations in heart rhythm intervals were associated with alterations in the spatial distribution of connexin 43. The incidence of arrhythmias was not different with age; however, valvular dysfunction was increased. These data suggest that aging in the female F344xBN rat heart is associated with changes in cardiac structure as well as function. Further investigation regarding other parameters of cardiac biochemistry and function is needed to better understand the normal compensated cardiovascular aging process in the female F344xBN.

Unmasking of oestrogen‐dependent changes in left ventricular structure and function in aged female rats: a potential model for pre‐heart failure with preserved ejection fraction

“…Female rats of up to 30 months of age show development of LV hypertrophy, dilatation and diastolic dysfunction (Fannin et al . ), while decreases in collagen area fraction have been reported (Hacker, ). In our study, using echocardiography, we document the development of mild eccentric chamber remodelling from 18 to 21 months of age, with no apparent changes in diastolic or systolic function, including EF.…”

“…In rats, unlike menopausal women, oestradiol levels during ageing can be near their younger counterpart even past 20 months of age (Fannin et al . ). Thus, ovariectomy is commonly used to examine the role that low oestrogen levels play in altering cardiac structure/function (Knowlton & Lee, ).…”

Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection

“…In aged mice and rat hearts, total and mitochondrial Cx43 expression are decreased (Boengler et al, 2007; Fannin et al, 2014; Watanabe et al, 2004; Zaman et al, 2014). Also lateralization of Cx43 is enhanced in aged cardiomyocytes (Dhein and Hammerath, 2001).…”

“…Also lateralization of Cx43 is enhanced in aged cardiomyocytes (Dhein and Hammerath, 2001). The increased heterogenety of Cx43 distribution correlates with age-associated alterations in heart rhythm and increased atrial fibrillation in patients (Nattel et al 2007; Fannin et al, 2014). There are differences regarding gender as Cx43 expression is higher in female compared to male hearts (Knezl et al, 2008; Tribulova et al, 2005).…”

The changes in cardiac physiology with aging and the implications for the treating oncologist

“…In normal aging, there is no change in overall cardiac mass, LV cavity size nor LVEF. However, decreased LV compliance leads to significant changes in diastolic function with a 50% reduction in the early diastolic filling rate by age 80 and increased cardiac filling pressures [10,11,[14][15][16][17][18]. To compensate, there is increased late diastolic filling, with atrial contraction contributing a larger proportion of ventricular filling.…”