Cardiac Morphology and Function in Senescent Rats: Gender-Related Differences

Forman, Daniel E.; Cittadini, Antonio; Azhar, Gohar; Douglas, Pamela S.; Wei, Jeanne Y.

doi:10.1016/s0735-1097(97)00411-7

Cited by 75 publications

(68 citation statements)

References 44 publications

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“…Cardiac structural measures in the adult (12-24 mo) FBN male rat were very similar to reported values from similar ages and various other strains with respect to LV mass-to-body weight ratio (5,8,9,20,21,28,36,37), anterior and posterior wall thicknesses (9,21,28,37), and LV diastolic dimension (1,5,9,21,23,28,37). LV function in the present study was also similar to that reported in 12-to 25-mo-old rats of various strains.…”

Section: Discussionsupporting

confidence: 90%

“…The efficacy of echocardiography in the rat model has been confirmed (10,40,41), and it has been used to evaluate treatment effects on cardiac function (34), to assess cardiac structural and functional characteristics of rats with surgically induced myocardial infarct (30) and hypertension (24,32), and in genetic models of hypertrophic heart failure (37). Only recently has there been a report on baseline echocardiographic values for normal adult rats (51) and age-associated changes in the female F344 rat heart (9).Although several studies have characterized the cardiovascular system in older rats (1,5,8,9,14,21,23,33,37), no study has examined functional and structural alterations over 30 mo of age. In this study we determined standard reference values for adult (12 mo) and aging (18 to 39 mo in 3-mo intervals) FBN male rat cardiovascular structure and function by using echocardiographic, hemodynamic, and histological measures.…”

mentioning

confidence: 99%

“…Although several studies have characterized the cardiovascular system in older rats (1,5,8,9,14,21,23,33,37), no study has examined functional and structural alterations over 30 mo of age. In this study we determined standard reference values for adult (12 mo) and aging (18 to 39 mo in 3-mo intervals) FBN male rat cardiovascular structure and function by using echocardiographic, hemodynamic, and histological measures.…”

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confidence: 99%

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Age-related changes in cardiac structure and function in Fischer 344 × Brown Norway hybrid rats

Hacker¹,

McKiernan²,

Douglas³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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The effects of aging on cardiovascular function and cardiac structure were determined in a rat model recommended for gerontological studies. A cross-sectional analysis assessed cardiac changes in male Fischer 344 ϫ Brown Norway F1 hybrid rats (FBN) from adulthood to the very aged (n ϭ 6 per 12-, 18-, 21-, 24-, 27-, 30-, 33-, 36-, and 39-mo-old group). Rats underwent echocardiographic and hemodynamic analyses to determine standard values for left ventricular (LV) mass, LV wall thickness, LV chamber diameter, heart rate, LV fractional shortening, mitral inflow velocity, LV relaxation time, and aortic/LV pressures. Histological analyses were used to assess LV fibrotic infiltration and cardiomyocyte volume density over time. Aged rats had an increased LV mass-to-body weight ratio and deteriorated systolic function. LV systolic pressure declined with age. Histological analysis demonstrated a gradual increase in fibrosis and a decrease in cardiomyocyte volume density with age. We conclude that, although significant physiological and morphological changes occurred in heart function and structure between 12 and 39 mo of age, these changes did not likely contribute to mortality. We report reference values for cardiac function and structure in adult FBN male rats through very old age at 3-mo intervals. hybrid rat; echocardiography CARDIAC STRUCTURE AND FUNCTION are remarkably similar among mammalian species, and the use of animal models has been extremely helpful in developing treatment strategies for alleviating heart disease in humans. Extending animal studies beyond young adult ages to very old ages may provide similar benefits to cardiovascular health of the growing aged population. In mammalian tissues, aging manifests as detrimental alterations in structure and function. Structural changes in the aging heart extend from cardiomyocyte cell loss, left ventricular (LV) hypertrophy, changes in ventricle chamber diameter, and collagen deposition (3, 13, 14), leading to overt functional changes such as lengthening of contraction and relaxation times and thus a decrease in heart rate (15), decreases in fractional shortening, decreased LV end-systolic pressure (15, 33), and reduced cardiac output. These normal aging changes do not necessarily contribute to morbidity but are clearly associated with the general decline observed with aging.The Fischer 344 (F344) rat has been a standard model of aging with an extensive database on this genotype (29). Even though the F344 rat has been widely used in research, concerns have been raised whether this specific strain is appropriate for all gerontological studies because of its overuse and some severe age-related pathologies (53). The National Institute on Aging and the National Center for Toxicological Research responded to these concerns and found that, among others, the Fischer 344 ϫ Brown Norway F1 hybrid rat (FBN) would complement the F344 aging studies (53). The FBN rat had significantly fewer pathological lesions compared with the F344 and a greater mean age for 50% mortality...

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Age-related changes in cardiac structure and function in Fischer 344 × Brown Norway hybrid rats

Hacker¹,

McKiernan²,

Douglas³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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show abstract

“…For T-H study, 6-and 22-month-old Fisher 344 rats were obtained through the National Institute of Aging (Bethesda, MD, USA). Several studies have characterized the cardiovascular system in the aged rat (13,14). Specifically, previous histological characterizations of aged rat heart have demonstrated fibrotic infiltration of left ventricle and decreased volume density of cardiomyocytes (15).…”

Section: Animalsmentioning

confidence: 99%

Aging Influences Cardiac Mitochondrial Gene Expression and Cardiovascular Function following Hemorrhage Injury

Jian

Yang

Chen

et al. 2010

Mol Med

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Cardiac dysfunction and mortality associated with trauma and sepsis increase with age. Mitochondria play a critical role in the energy demand of cardiac muscles, and thereby on the function of the heart. Specific molecular pathways responsible for mitochondrial functional alterations after injury in relation to aging are largely unknown. To further investigate this, 6-and 22-monthold rats were subjected to trauma-hemorrhage (T-H) or sham operation and euthanized following resuscitation. Left ventricular tissue was profiled using our custom rodent mitochondrial gene chip (RoMitochip). Our experiments demonstrated a declined left ventricular performance and decreased alteration in mitochondrial gene expression with age following T-H and we have identified c-Myc, a pleotropic transcription factor, to be the most upregulated gene in 6-and 22-month-old rats after T-H. Following T-H, while 142 probe sets were altered significantly (39 up and 103 down) in 6-month-old rats, only 66 were altered (30 up and 36 down) in 22-month-old rats; 36 probe sets (11 up and 25 down) showed the same trend in both groups. The expression of c-Myc and cardiac death promoting gene Bnip3 were increased, and Pgc1-α and Ppar-α a decreased following T-H. Eleven tRNA transcripts on mtDNA were upregulated following T-H in the aged animals, compared with the sham group. Our observations suggest a cmyc-regulated mitochondrial dysfunction following T-H injury and marked decrease in age-dependent changes in the transcriptional profile of mitochondrial genes following T-H, possibly indicating cellular senescence. To our knowledge, this is the first report on mitochondrial gene expression profile following T-H in relation to aging.

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“…Gender may also be a factor as women develop an asymptomatic form of alcoholic cardiomyopathy with a lower total lifetime consumption of alcohol (12,70). In contrast, alcohol-induced myocardial dysfunction appears more severe in male compared with female rats (14,15), and gender-related differences in cardiac morphology and function have been noted in aged versus adult animals (16). Currently, the overwhelming majority of studies on alcohol-induced changes in heart have been performed in males, thereby potentially limiting our understanding of disease etiology.…”

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confidence: 99%

Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats

Lang

2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Lang CH, Korzick DH. Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats. Am J Physiol Regul Integr Comp Physiol 306: R23-R33, 2014. First published November 13, 2013 doi:10.1152/ajpregu.00414.2013.-The purpose of this study was to assess whether the deleterious effect of chronic alcohol consumption differs in adult and aged female rats. To address this aim, adult (4 mo) and aged (18 mo) F344 rats were fed a nutritionally complete liquid diet containing alcohol (36% total calories) or an isocaloric isonitrogenous control diet for 20 wk. Cardiac structure and function, assessed by echocardiography, as well as myocardial protein synthesis and proteolysis did not differ in either alcohol-versus control-fed adult rats or in adult versus aged controlfed rats. In contrast, cardiac function was impaired in alcohol-fed aged rats compared with age-matched control rats. Additionally, alcohol feeding decreased cardiac protein synthesis that was associated with decreased phosphorylation of 4E-BP1 and S6K1. This reduction in mammalian target of rapamycin (mTOR) kinase activity was associated with reduced eIF3f and binding of both Raptor and eIF4G to eIF3. Proteasome activity was increased in alcohol-fed aged rats with a coordinate elevation in the E3 ligases atrogin-1 and muscle RINGfinger protein-1 (MuRF1). These changes were associated with increased regulated in development and DNA damage response 1 (REDD1) and phosphorylation of AMP-activated protein kinase (AMPK) but no increase in AKT or forkhead transcription factor (FOXO)3 phosphorylation. Finally, markers of autophagy (e.g., LC3B, Atg7, Atg12) and TNF-␣ were increased to a greater extent in alcohol-fed aged rats. These data demonstrate that aged female rats exhibit an enhanced sensitivity to alcohol compared with adult animals. Our data are consistent with a model whereby alcohol increases proteolysis via FOXO-independent increase in atrogin-1, which degrades eIF3f and therefore impairs formation of a functional preinitiation complex and protein synthesis.

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Cardiac Morphology and Function in Senescent Rats: Gender-Related Differences

Cited by 75 publications

References 44 publications

Age-related changes in cardiac structure and function in Fischer 344 × Brown Norway hybrid rats

Age-related changes in cardiac structure and function in Fischer 344 × Brown Norway hybrid rats

Aging Influences Cardiac Mitochondrial Gene Expression and Cardiovascular Function following Hemorrhage Injury

Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats

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