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

2006 ◽  
Vol 290 (1) ◽  
pp. H304-H311 ◽  
Author(s):  
Timothy A. Hacker ◽  
Susan H. McKiernan ◽  
Pamela S. Douglas ◽  
Jonathan Wanagat ◽  
Judd M. Aiken

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 × Brown Norway F1 hybrid rats (FBN) from adulthood to the very aged ( n = 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.

2002 ◽  
Vol 9 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Stephen B. Harrap ◽  
Vennetia R. Danes ◽  
Justine A. Ellis ◽  
Cory D. Griffiths ◽  
Elizabeth F. Jones ◽  
...  

We describe a new line of rats with inherited cardiomyocyte and ventricular hypertrophy. From a second-generation cross of spontaneously hypertensive and Fischer 344 rats, we selected for low blood pressure and either high or low echocardiographic left ventricular (LV) mass over four generations to establish the hypertrophic heart rat (HHR) and normal heart rat (NHR) lines, respectively. After 13 generations of inbreeding, HHR had significantly greater ( P < 0.0001) LV mass-to-body weight ratio (2.68 g/kg, SE 0.14) than NHR matched for age (1.94 g/kg, SE 0.02) or body weight (2.13 g/kg, SE 0.03). The isolated cardiomyocytes of HHR were significantly ( P < 0.0001) longer and wider (161 μm, SE 0.83; 35.6 μm, SE 2.9) than NHR (132 μm, SE 1.2; 29.5 μm, SE 0.35). Telemetric 24-h recordings of mean arterial pressure revealed no significant differences between HHR and NHR. The HHR offers a new model of primary cardiomyocyte hypertrophy with normal blood pressure in which to examine genotypic causes and pathogenetic mechanisms of hypertrophy and its complications.


1989 ◽  
Vol 257 (1) ◽  
pp. H289-H296 ◽  
Author(s):  
A. DeFelice ◽  
R. Frering ◽  
P. Horan

Male rats were monitored for 8 mo after severe myocardial infarction (MI) to chronicle hemodynamic and left ventricular (LV) functional changes. Blood pressure (BP), heart rate (HR), cardiac output index (CO), regional blood flow, and systemic vascular resistance (SVR) were measured with catheters and radiolabeled microspheres at 4, 7, 10, 20, and 35 wk after coronary artery ligation (n = 10–16/group) or sham operation (control; n = 9–14/group). At 4 wk, 43 +/- 1% of the LV circumference was scarred, peak LV BP, LV dP/dtmax, mean BP, SVR, and HR were 11–38% less than control (P less than 0.05), and LV end-diastolic pressure (LVEDP) was increased by 313% (P less than 0.05). Mean BP, LVEDP, LVBP, and LV dP/dtmax did not further deviate after 4 wk. However, CO and SVR changed progressively and were 67 and 33%, respectively, of control by 35 wk (P less than 0.05) when blood flow to stomach, small intestine, and kidney was 55, 38, and 27% of control. Lung and heart weights were significantly increased by 148 and 22% at 4 wk, and remained elevated, and lung dry weight-to-wet weight ratio was reduced at 7 and 10 wk. Thus the trajectory of rats with healed severe MI reflects progressive cardiac decompensation, cardiac output redistribution, and terminal heart failure.


2018 ◽  
Vol 9 (1) ◽  
pp. 22-30 ◽  
Author(s):  
Jiahui Li ◽  
Aili Li ◽  
Jiali Wang ◽  
Yu Zhang ◽  
Ying Zhou

Purpose: Cardiac valve calcification (VC) is very common in patients on hemodialysis. However, the definite effect of VC on left ventricular (LV) geometry and function in this population is unknown, especially when LV ejection fraction (LVEF) is normal. The aim of this study was to determine the effect of VC on LV geometry and function in long-term hemodialysis patients by conventional echocardiography and two-dimensional speckle tracking echocardiography (2D-STE). Methods: A total of 47 hemodialysis patients (2–3 times weekly for 5 years or more) were enrolled in this study. Cardiac VC was defined as bright echoes of more than 1 mm on one or more cusps of the aortic valve or mitral valve or mitral annulus using echocardiography as the screening method. LV longitudinal global strain (GLS) was assessed on the apical four-chamber view and calculated as the mean strain of 6 segments. LV global circumferential strain was acquired on the LV short axis view at the level of papillary muscles. Results: Twenty-five patients with VC had higher mean values of interventricular septum thickness, LV posterior wall thickness, LV mass index, relative wall thickness, and LV mass/end-diastolic volume than 22 patients without VC (p < 0.05, respectively), indicating more obvious LV hypertrophy (LVH). VC patients had higher mitral annular E/E′ values, especially at the septal side representing increased LV filling pressure compatible with diastolic dysfunction, while only the E/E′ ratio of the septal side was significantly different between the 2 groups (16.7 ± 4.1 vs. 12.3 ± 4.4, p < 0.01). When assessed by GLS, LV longitudinal systolic function was also lower in in patients with VC compared with those without VC (–0.18 ± 0.03 vs. –0.25 ± 0.04; p < 0.01). Conclusions: Cardiac VC diagnosed by echocardiography when it occurs in long-term hemodialysis patients may indicate more severe LVH, myocardial damage, and worse heart function in comparison to those without VC. Tissue Doppler imaging and 2D-STE can detect the subtle change of heart function in this population in the early stage of LV dysfunction when LVEF is normal.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Matthew A Allison ◽  
Jianwen Cai ◽  
Ankit Desai ◽  
Barry Hurwitz ◽  
Ai Ni ◽  
...  

Background: The purpose of this study was to determine the magnitudes and significances of the associations between adiposity and echocardiographically determined measures of left ventricular (LV) structure and function in a diverse cohort of Hispanic/Latino adults. Methods: Subjects were 1,350 adult men and women participants of the Hispanic Communities Health Study - Study of Latinos (HCHS-SOL) who enrolled in an ancillary study to determine cardiac structure and function by echocardiography. In addition to echocardiography, subjects were evaluated by extensive survey information, relevant physical measurements (to include bioelectrical impedance) and fasting blood assays. Results: The mean age was 56.1 years and 57% were female. Twenty-six percent were Mexican American, 25% Cuban American, 18% Dominican American, 17% Puerto Rican American, 8% Central American and 7% South American. Overall, the mean ejection fraction was 60.5%, while the mean stroke volume was 70 ml, end diastolic volume 83 ml, fractional shortening 31% and cardiac output 4.5 L/min. Results of multivariable linear regression adjusted for age, gender, hypertension, diabetes, dyslipidemia, cigarette smoking, family history of coronary heart disease, C-reactive protein and chronic kidney disease revealed that each 1-unit increment in body mass index (BMI) and fat mass (FM) by impedance was associated with 0.64 and 0.25 (p < 0.01 for both) higher LV mass index (to height), while a 0.1 unit increment in the waist to hip ratio (WHR) was associated with 3.2 higher LV mass index. Concomitantly, each 1-unit increment in BMI and FM was associated with 7 and 3% (p < 0.01 for each) higher odds of LV hypertrophy, while a 0.1 unit increment in WHR was associated with 78% higher odds for LV hypertrophy (p < 0.01). On the other hand, none of these variables were significantly associated with ejection fraction. There were no significant interactions between the anthropometric variables and the different Hispanic groups for LV mass index or hypertrophy. Conclusions: Among Hispanics/Latinos from different cultural backgrounds, and by three measures of body composition (BMI, FM and WHR), higher levels of adiposity are significantly associated with higher LV mass indexed for height and the odds for hypertrophy, while not being associated with better or worse ejection fraction.


2004 ◽  
Vol 59 (8) ◽  
pp. B801-B808 ◽  
Author(s):  
I. M. Olfert ◽  
J. Balouch ◽  
O. Mathieu-Costello

2011 ◽  
Vol 89 (4) ◽  
pp. 277-288 ◽  
Author(s):  
Nazli N. Sozmen ◽  
Erkan Tuncay ◽  
Ayca Bilginoglu ◽  
Belma Turan

Increasing evidence shows a marked beneficial effect with β-blockers in heart dysfunction via scavenging reactive oxygen species. Previously we showed that chronic treatment with either timolol or propranolol possessed similar beneficial effects for heart function in male rats as age increased, whereas only timolol exerted similar benefits in female rats. Therefore, in this study, we aimed first to examine the cellular bases for age-related alterations in excitation–contraction coupling in ventricular myocytes from female rats and, second, to investigate the hypothesis that age-related changes in [Ca2+]ihomeostasis and receptor-mediated system can be prevented with chronic timolol treatment. Chronic timolol treatment of 3-month-old female rats abolished age-related decrease in left ventricular developed pressure and the attenuated responses to β-adrenoreceptor stimulation. It also normalized the altered parameters of [Ca2+]itransients, decreased Ca2+loading of sarcoplasmic reticulum and increased basal [Ca2+]i, and decreased L-type Ca2+currents in 12-month-old female rats compared with the 3-month-old group. Adenylyl cyclase activity, β-adrenoreceptor affinity to its agonist, and β-adrenoreceptor density of the 12-month-old group are normalized to those of the 3-month-old group. Moreover, timolol treatment prevented dysfunction of the antioxidant system, including increased lipid peroxidation, decreased ratio of reduced glutathione to oxidized glutathione, and decreased activities of thioredoxin reductase and glucose-6-phosphate dehydrogenase, in the left ventricle of hearts from the 12-month-old group. Our data confirmed that aging-related early myocardial impairment is primarily related to a dysfunctional antioxidant system and impairment of Ca2+homeostasis, which can be prevented with chronic timolol treatment.


1991 ◽  
Vol 261 (4) ◽  
pp. H1011-H1018 ◽  
Author(s):  
R. J. Tomanek ◽  
T. J. Wessel ◽  
D. G. Harrison

Angiogenic response of the myocardial capillary bed to long-term (7 mo) renovascular hypertension (one-kidney, one-clip) was assessed in eight mongrel dogs and compared with seven control dogs. Image analyses of histological sections from four transmural specimen sites of left ventricular (LV) free wall were performed. While mean cross-sectional cardiocyte area increased in all transmural layers (epi-endo) in dogs with LV hypertrophy (LVH), the greatest increases occurred in the inner layers. Although capillary length density was significantly lower in two of the four transmural regions of LVH dogs, these decrements were much less than the lateral expansion of cardiocytes as indicated by cross-sectional areas. Calculations of total capillary length indicate that approximately one-fifth of the capillary bed in LVH dogs was formed during the 7-mo period of hypertension in hypertrophied hearts. Capillary volume and surface densities in LVH dogs decreased to a greater extent due to a larger population of capillaries with lumen diameters less than 4 microns. Capillary volume density in LVH dogs was remarkably similar across the wall despite large transmural differences in cardiocyte hypertrophy. LVH did not alter the log SD of capillary domains, a measure of the heterogeneity of spacing, or capillary orientation (degree or anisotropy). These data support several important conclusions regarding long-term hypertension-induced LVH in dogs. First, although capillary growth does not fully compensate for the increase in LV mass, a myriad of new capillaries are formed as indicated by a substantial increase in total capillary length. This growth minimizes the increase in intercapillary distance characteristic of LVH.(ABSTRACT TRUNCATED AT 250 WORDS)


2003 ◽  
Vol 95 (4) ◽  
pp. 1739-1745 ◽  
Author(s):  
Jeremy M. LaMothe ◽  
Russell T. Hepple ◽  
Ronald F. Zernicke

Rodents are commonly used as models for human aging because of their relatively short life span, the ease of obtaining age-specific tissue samples, and lower cost. However, age-associated disease may confound inbred animal studies. For example, numerous physiologically significant lesions, such as chronic nephropathy, are more common in aged Fischer 344 (F344) rats than in other strains (Bronson RT, Genetic Effects of Aging, 1990). Conversely, F344 × Brown-Norway F1-hybrid (F344BN) rats, developed by the National Institute on Aging for aging research, live considerably longer and have fewer pathologies at any given age vs. inbred strains (Lipman RD, Chrisp CE, Hazzard DG, and Bronson RT, J Gerontol A Biol Sci Med Sci 51: 54-59, 1996). To our knowledge, there are no data regarding the effect of age on bone geometry and mechanics in this strain of rat. Furthermore, caloric restriction (CR) extends the mean and maximal life span of animals and significantly reduces age-associated disease but may have adverse consequences for bone growth and mechanics. Thus we investigated the effects of age and CR on bone geometry and mechanics in the axial and appendicular skeleton of F344 Brown-Norway rats. Ad libitum fed rats were assessed at 8 mo (young adult; n = 6), 28 mo (late middle age; n = 5), and 36 mo (senescence; n = 6). CR rats were assessed at 28 mo ( n = 6). Tibiae and the sixth lumbar vertebrae (L6) were dissected, scanned (micro-computed tomography) to determine geometry, and tested mechanically. From 8 to 36 mo, there were no significant changes in L6 geometry, and only the cross-sectional moment of inertia changed (increased) with the tibia. CR-induced body mass reductions accounted for changes in L6 load at proportional limit, maximal load, and stiffness (structural properties), but altered tibial structural properties were independent of body mass. In tibiae, geometric changes dominated alterations in structural properties. Those data demonstrated that, whereas aging in ad libitum-fed animals induced minor changes in bone mechanics, axial and appendicular bones were adversely influenced by CR in late-middle-aged animals in different manners.


2008 ◽  
Vol 93 (7) ◽  
pp. 863-871 ◽  
Author(s):  
Andrew C. Betik ◽  
David J. Baker ◽  
Daniel J. Krause ◽  
Marina J. McConkey ◽  
Russell T. Hepple

1993 ◽  
Vol 75 (2) ◽  
pp. 972-978 ◽  
Author(s):  
G. D. Cartee ◽  
C. Briggs-Tung ◽  
E. W. Kietzke

Very young rats (< 2 mo) have a persistent increase in insulin-stimulated glucose transport rate in skeletal muscle for several hours after completing a bout of exercise. We studied the effect of exercise on the glucose transport activity of isolated epitrochlearis muscles from male Fischer 344/Brown Norway F1 hybrid rats across a wide range of the life-span (at 3.5, 13, and 25 mo). The stimulation of 3-O-methylglucose (3-MG) accumulation by a submaximally effective insulin concentration (100 microU/ml) was enhanced (50–75%) 4 h after exercise, regardless of age. In contrast, the 3-MG transport rate with 20,000 microU/ml insulin was enhanced after exercise only in the youngest rats (35%), and this increased responsiveness occurred despite no changes in muscle total GLUT-4 levels. In addition, epitrochlearis GLUT-4 levels were reduced by 29% between 3.5 and 13 mo of age in sedentary rats but did not decline further between 13 and 25 mo of age. GLUT-4 levels were moderately but significantly (P < 0.05) related (r = 0.554) to epitrochlearis muscle capacity for insulin-stimulated 3-MG transport.


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