Effects of age on mechanical and structural properties of myocardium of Fischer 344 rats

Anversa, Piero; Puntillo, E.; Никитин, П.В.; Olivetti, G; Capasso, J. M.; Sonnenblick, Edmund H.

doi:10.1152/ajpheart.1989.256.5.h1440

Cited by 31 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in contrast to analysis of single cardiomyocytes from 32-to 33-mo-old female Fischer 344 ϫ Brown Norway rats where no change in relaxation was observed with age (48). However, other rat strains do show impaired relaxation in single cardiomyocytes (4,6,13). The methodological differences in measuring relaxation in a whole animal versus an isolated cell preparation likely accounts for the differences.…”

Section: Discussionmentioning

confidence: 74%

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

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 74%

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

View full text Add to dashboard Cite

show abstract

“…Fig. 2 ( 19), the size of the muscles used in this study did not limit oxygenation of the core of the muscles producing cellular damage. This was confirmed quantitatively, since the volume fraction of myocytes and interstitial compartment in muscles exposed to moderate levels of tension was 86±1.0 and 14 1.0, whereas the corresponding values in muscles kept at high tension were 87±2.0 and 13+±2.0.…”

Section: Resultsmentioning

confidence: 96%

Stretch-induced programmed myocyte cell death.

Cheng

Li²,

Kajstura³

et al. 1995

J. Clin. Invest.

594

313

View full text Add to dashboard Cite

To determine the effects of loading on active and passive tensions, programmed cell death, superoxide anion formation, the expression of Fas on myocytes, and side-to-side slippage of myocytes, papillary muscles were exposed to 7-8 and 50 mN/mm2 and these parameters were measured over a 3-h period. Overstretching produced a 21-and a 2.4-fold increase in apoptotic myocyte and nonmyocyte cell death, respectively. Concurrently, the generation of reactive oxygen species increased 2.4-fold and the number of myocytes labeled by Fas protein 21-fold. Moreover, a 15% decrease in the number of myocytes included in the thickness of the papillary muscle was found in combination with a 7% decrease in sarcomere length and the inability of muscles to maintain stable levels of passive and active tensions. The addition of the NO-releasing drug, C87-3754, prevented superoxide anion formation, programmed cell death, and the alterations in active and passive tensions with time of overloaded papillary muscles. In conclusion, overstretching appears to be coupled with oxidant stress, expression of Fas, programmed cell death, architectural rearrangement of myocytes, and impairment in force development of the myocardium. (J. Clin. Invest. 1995. 96:2247-2259

show abstract

“…There is increasing evidence demonstrating an aging-associated development of cardiovascular dysfunction (Anversa et al, 1989;Capasso et al, 1990;Hatake et al, 1990;Taddei et al, 1995;Higashi et al, 1997;van der Loo et al, 2000;Hamilton et al, 2001;Boluyt et al, 2004). The mechanisms responsible for this age-related cardiovascular dysfunction have not yet been clearly established.…”

Section: Discussionmentioning

confidence: 99%

“…The Fischer rat has served as a model to study the mechanisms of the aging-induced changes in the cardiovascular system (Anversa et al, 1989;Capasso et al, 1990;Boluyt et al, 2004). In this model, decreased cardiac performance and the development of progressive heart failure were reported after the age of 20 months (Anversa et al, 1989).…”

Section: Poly(adp-ribose) Polymerase and Cardiovascular Aging 487mentioning

confidence: 99%

A New, Potent Poly(ADP-ribose) Polymerase Inhibitor Improves Cardiac and Vascular Dysfunction Associated with Advanced Aging

Pacher

Vaslin

Benkó

et al. 2004

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Increased production of reactive oxygen and nitrogen species has recently been implicated in the pathogenesis of cardiac and endothelial dysfunction associated with atherosclerosis, hypertension, and aging. Oxidant-induced cell injury triggers the activation of nuclear enzyme poly(ADP-ribose) polymerase (PARP), which in turn contributes to cardiac and vascular dysfunction in various pathophysiological conditions including diabetes, reperfusion injury, circulatory shock, and aging. Here, we investigated the effect of a new PARP inhibitor, INO-1001, on cardiac and endothelial dysfunction associated with advanced aging using Millar's new Aria pressure-volume conductance system and isolated aortic rings. Young adult (3 months old) and aging (24 months old) Fischer rats were treated for 2 months with vehicle, or the potent PARP inhibitor INO-1001. In the vehicle-treated aging animals, there was a marked reduction of both systolic and diastolic cardiac function and loss of endothelial relaxant responsiveness of aortic rings to acetylcholine. Treatment with INO-1001 improved cardiac performance in aging animals and also acetylcholine-induced, nitric oxide-mediated vascular relaxation. Thus, pharmacological inhibition of PARP may represent a novel approach to improve cardiac and vascular dysfunction associated with aging.Poly(ADP-ribose) polymerase (PARP) is the most abundant nuclear enzyme of eukaryotic cells. When activated by DNA single-strand breaks, PARP initiates an energy-consuming cycle by transferring ADP ribose units from NAD ϩ to nuclear proteins. This process results in rapid depletion of the intracellular NAD ϩ and ATP pools, slowing the rate of glycolysis and mitochondrial respiration, eventually leading to cellular dysfunction and death (reviewed in Virá g and Szabó 2002). PARP can also regulate the expression of various inflammatory mediators such as inducible nitric-oxide synthase, tumor necrosis factor-␣, and intracellular adhesion molecule-1. Suppression of expression of inducible nitric-oxide synthase, tumor necrosis factor-␣, and intracellular adhesion molecule-1 has been reported in PARP-deficient mice and in the presence of pharmacological inhibitors of the enzyme (reviewed in Virá g and Szabó 2002).Overactivation of PARP represents an important mechanism of tissue damage in pathological conditions associated with oxidative/nitrosative stress, including myocardial reperfusion injury, stroke, circulatory shock, autoimmune ␤-cell destruction, diabetic complications, and various forms of heart failure (Szabó et al., 1997;Thiemermann et al., 1997;Zingarelli et al., 1998; Soriano et al., 2001a,b; Pacher et al., 2002a-f;Virá g and Szabó 2002;Szabó 2004a

show abstract

Effects of age on mechanical and structural properties of myocardium of Fischer 344 rats

Cited by 31 publications

References 0 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

Stretch-induced programmed myocyte cell death.

A New, Potent Poly(ADP-ribose) Polymerase Inhibitor Improves Cardiac and Vascular Dysfunction Associated with Advanced Aging

Contact Info

Product

Resources

About