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  • 1
    Online Resource
    Online Resource
    Left ventricular response to sustained volume overload from chronic aortic valve regurgitation in rats
    Elsevier BV ; 2003
    In:  Journal of Cardiac Failure Vol. 9, No. 2 ( 2003-4), p. 128-140
    Details
    In: Journal of Cardiac Failure, Elsevier BV, Vol. 9, No. 2 ( 2003-4), p. 128-140
    Type of Medium: Online Resource
    ISSN: 1071-9164
    URL: Article
    DOI: 10.1054/jcaf.2003.17
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2003
    detail.hit.zdb_id: 2048826-9
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  • 2
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    Effectiveness of β-Blockade in Experimental Chronic Aortic Regurgitation
    Ovid Technologies (Wolters Kluwer Health) ; 2004
    In:  Circulation Vol. 110, No. 11 ( 2004-09-14), p. 1477-1483
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 110, No. 11 ( 2004-09-14), p. 1477-1483
    Abstract: Background— Past studies have suggested that the adrenergic system becomes abnormally activated in chronic volume overload, such as in severe aortic valve regurgitation (AR). However, the effectiveness of agents directed against this adrenergic activation has never been adequately tested in chronic AR. We therefore tested the effects of metoprolol treatment on the left ventricular (LV) function and remodeling in severe chronic AR in rats. Methods and Results— Severe AR was created in adult male Wistar rats by retrograde puncture of the aortic leaflets under echocardiographic guidance. Two weeks later, some animals received metoprolol treatment (25 mg/kg) orally for 24 weeks, and some were left untreated. LV dimensions, ejection fraction, and filling parameters were evaluated by echocardiography. Hearts were harvested at 1, 2, 14, and 180 days for the evaluation of hypertrophy, β-adrenergic receptor status, and extracellular matrix remodeling. We found that metoprolol treatment prevented LV dilatation and preserved the ejection fraction and filling parameters compared with untreated animals. Metoprolol increased the expression of β 1 -adrenoreceptor mRNA and reduced G protein receptor kinase 2 levels. Collagen I and III mRNA levels were reduced. Cardiac myocyte hypertrophy was also prevented. Conclusions— In our experimental model of severe AR, metoprolol treatment had a significant beneficial global effect on LV remodeling and function. These results suggest that the adrenergic system is important in the development of volume-overload cardiomyopathy in AR and that adrenergic-blocking agents may play a role in the treatment of this disease.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.0000141733.55236.9D
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2004
    detail.hit.zdb_id: 1466401-X
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  • 3
    Online Resource
    Online Resource
    Early endothelial dysfunction in cholesterol-fed rabbits: a non-invasive in vivo ultrasound study.
    Springer Science and Business Media LLC ; 2004
    In:  Cardiovascular Ultrasound Vol. 2, No. 1 ( 2004-7)
    Details
    In: Cardiovascular Ultrasound, Springer Science and Business Media LLC, Vol. 2, No. 1 ( 2004-7)
    Type of Medium: Online Resource
    ISSN: 1476-7120
    URL: Article
    DOI: 10.1186/1476-7120-2-10
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2004
    detail.hit.zdb_id: 2105610-9
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  • 4
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    Benefits of long-term β-blockade in experimental chronic aortic regurgitation
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 294, No. 4 ( 2008-04), p. H1888-H1895
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 294, No. 4 ( 2008-04), p. H1888-H1895
    Abstract: The objective of this study was to assess the long-term effects of β-blockade on survival and left ventricular (LV) remodeling in rats with aortic valve regurgitation (AR). The pharmacological management of chronic AR remains controversial. No drug has been definitively proven to delay the need for valve replacement or to affect morbidity and/or mortality. Our group has reported that the adrenergic system is activated in an animal model of AR and that adrenergic blockade may help maintain normal LV function. The effects of prolonged treatment with a β-blocker are unknown. Forty Wistar rats with severe AR were divided into 2 groups of 20 animals each and treated with metoprolol (Met, 25 mg·kg −1 ·day −1 ) or left untreated for 1 yr. LV remodeling was evaluated by echocardiography. Survival was assessed by Kaplan-Meir curves. Hearts were harvested for tissue analysis. All Met-treated animals were alive after 6 mo vs. 70% of untreated animals. After 1 yr, 60% of Met-treated animals were alive vs. 35% of untreated animals ( P = 0.028). All deaths, except one, were sudden. There were no differences in LV ejection fraction (all 〉 50%) or LV dimensions. LV mass tended to be lower in the Met-treated group. There was less subendocardial fibrosis in this group, as well as lower LV filling pressures (LV end-diastolic pressure). β-Adrenergic receptor ratio (β 1 /β 2 ) was improved. One year of treatment with Met was well tolerated. Met improved 1-yr survival, minimized LV hypertrophy, improved LV filling pressures, decreased LV subendocardial fibrosis, and helped restore the β-adrenergic receptor ratio.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.01286.2007
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 5
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    Angiotensin-converting enzyme inhibitor captopril prevents volume overload cardiomyopathy in experimental chronic aortic valve regurgitation
    Canadian Science Publishing ; 2004
    In:  Canadian Journal of Physiology and Pharmacology Vol. 82, No. 3 ( 2004-03-01), p. 191-199
    Details
    In: Canadian Journal of Physiology and Pharmacology, Canadian Science Publishing, Vol. 82, No. 3 ( 2004-03-01), p. 191-199
    Abstract: The efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of chronic aortic regurgitation (AR) is not well established and remains controversial. The mechanisms by which ACEIs may protect against left-ventricular (LV) volume overload are not well understood, and clinical trials performed until now have yielded conflicting results. This study was therefore performed to assess the effectiveness of two different doses of the ACEI captopril in a rat model of chronic AR. We compared the effects of a 6-month low-dose (LD) (25 mg/kg) or higher dose (HD) (75 mg/kg) treatment with captopril on LV function and hypertrophy in Wistar rats with severe AR. Untreated animals developed LV eccentric hypertrophy and systolic dysfunction. LD treatment did not prevent hypertrophy and provided modest protection against systolic dysfunction. HD treatment preserved LV systolic function and dimensions and tended to slow hypertrophy. The cardiac index remained high and similar among all AR groups, treated or not. Tissue renin–angiotensin system (RAS) analysis revealed that ACE activity was increased in the LVs of AR animals and that only HD treatment significantly decreased angiotensin II receptor mRNA levels. Fibronectin expression was increased in the LV or AR animals, but HD treatment almost completely reversed this increase. The ACE inhibitor captopril was effective at high doses in this model of severe AR. These effects might be related to the modulation of tissue RAS and the control of fibrosis.Key words: aortic valve, insufficiency, rat, echocardiography, volume overload, ACE inhibitors.
    Type of Medium: Online Resource
    ISSN: 0008-4212 , 1205-7541
    URL: Article
    DOI: 10.1139/y04-005
    Language: English
    Publisher: Canadian Science Publishing
    Publication Date: 2004
    detail.hit.zdb_id: 2004356-9
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  • 6
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    Online Resource
    Moderate Exercise Training Improves Survival and Ventricular Remodeling in an Animal Model of Left Ventricular Volume Overload
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Circulation: Heart Failure Vol. 2, No. 5 ( 2009-09), p. 437-445
    Details
    In: Circulation: Heart Failure, Ovid Technologies (Wolters Kluwer Health), Vol. 2, No. 5 ( 2009-09), p. 437-445
    Abstract: Background— Exercise training has beneficial effects in patients with heart failure, although there is still no clear evidence that it may impact on their survival. There are no data regarding the effects of exercise in subjects with chronic left ventricular (LV) volume overload. Using a rat model of severe aortic valve regurgitation (AR), we studied the effects of long-term exercise training on survival, development of heart failure, and LV myocardial remodeling. Methods and Results— One hundred sixty male adult rats were divided in 3 groups: sham sedentary (n=40), AR sedentary (n=80), and AR trained (n=40). Training consisted in treadmill running for up to 30 minutes, 5 times per week for 9 months, at a maximal speed of 20 m/minute. All sham-operated animals survived the entire course of the protocol. After 9 months, 65% of trained animals were alive compared with 46% of sedentary ones ( P =0.05). Ejection fractions remained in the normal range (all above 60%) and LV masses between AR groups were similar. There was significantly less LV fibrosis in the trained group and lower LV filling pressures and improved echocardiographic diastolic parameters. Heart rate variability was also improved by exercise. Conclusion— Our data show that moderate endurance training is safe, does not increase the rate of developing heart failure, and most importantly, improves survival in this animal model of chronic LV volume overload. Exercise improved LV diastolic function, heart rate variability, and reduced myocardial fibrosis.
    Type of Medium: Online Resource
    ISSN: 1941-3289 , 1941-3297
    URL: Article
    DOI: 10.1161/CIRCHEARTFAILURE.108.845487
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
    detail.hit.zdb_id: 2428100-1
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  • 7
    Online Resource
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    Early responses of the left ventricle to pressure overload in Wistar rats
    Elsevier BV ; 2008
    In:  Life Sciences Vol. 82, No. 5-6 ( 2008-1), p. 265-272
    Details
    In: Life Sciences, Elsevier BV, Vol. 82, No. 5-6 ( 2008-1), p. 265-272
    Type of Medium: Online Resource
    ISSN: 0024-3205
    URL: Article
    DOI: 10.1016/j.lfs.2007.11.008
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2008
    detail.hit.zdb_id: 2013911-1
    SSG: 12
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  • 8
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    Impact of Anesthesia on Echocardiographic Evaluation of Systolic and Diastolic Function in Rats
    Elsevier BV ; 2006
    In:  Journal of the American Society of Echocardiography Vol. 19, No. 12 ( 2006-12), p. 1520-1525
    Details
    In: Journal of the American Society of Echocardiography, Elsevier BV, Vol. 19, No. 12 ( 2006-12), p. 1520-1525
    Type of Medium: Online Resource
    ISSN: 0894-7317
    URL: Article
    DOI: 10.1016/j.echo.2006.06.011
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2006
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  • 9
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    Online Resource
    Dobutamine stress echocardiography in healthy adult male rats
    Springer Science and Business Media LLC ; 2005
    In:  Cardiovascular Ultrasound Vol. 3, No. 1 ( 2005-12)
    Details
    In: Cardiovascular Ultrasound, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2005-12)
    Abstract: Dobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response. Methods 15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intravenously under continuous imaging of the heart by a 12 MHz ultrasound probe. Results Dobutamine stress echocardiography reduced gradually LV diastolic and systolic dimensions. Ejection fraction increased by a mean of +24% vs. baseline. Heart rate increased progressively without reaching a plateau. Changes in LV dimensions and ejection fraction reached a plateau after a mean of 4 minutes at a constant infusion rate. Conclusion DSE can be easily performed in rats. The normal response is an increase in heart rate and ejection fraction and a decrease in LV dimensions. A plateau in echocardiographic measurements is obtained after 4 minutes of a constant infusion rate in most animals.
    Type of Medium: Online Resource
    ISSN: 1476-7120
    URL: Article
    DOI: 10.1186/1476-7120-3-34
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2005
    detail.hit.zdb_id: 2105610-9
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  • 10
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    Comparative Study of Vasodilators in an Animal Model of Chronic Volume Overload Caused by Severe Aortic Regurgitation
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Circulation: Heart Failure Vol. 2, No. 1 ( 2009-01), p. 25-32
    Details
    In: Circulation: Heart Failure, Ovid Technologies (Wolters Kluwer Health), Vol. 2, No. 1 ( 2009-01), p. 25-32
    Abstract: Background— Aortic regurgitation (AR) is a disease of chronic left ventricular (LV) volume overload. Over time, AR will lead to LV dilatation, hypertrophy, and loss of function. There is currently no medical treatment proven effective to slow the evolution of this cardiomyopathy. Vasodilators were once thought to have protective effects, but recent publications have cast some doubts about their effectiveness. We hypothesized that drugs targeting the renin-angiotensin system should be more effective than those having no direct effect on the renin-angiotensin system. Methods and Results— We designed a protocol comparing the effects of 3 vasodilators in a rat AR model (n=9 to 11 animals per group). The effects of a 6-month treatment of (1) nifedipine, (2) captopril, or (3) losartan were compared in male AR rats. Sham-operated and untreated AR animals were used as controls. Nifedipine-treated animals displayed hemodynamics, LV dilatation, hypertrophy, and loss of function similar to those of the untreated group. Both captopril and losartan were effective in improving hemodynamics, slow LV dilatation, hypertrophy, and dysfunction. Gene expression analysis confirmed the lack of effects of the nifedipine treatment at the molecular level. Conclusions— Using an animal model of severe AR, we found that vasodilators targeting the renin-angiotensin system were effective to slow the development of LV remodeling and to preserve LV function. As recently shown in the most recent human clinical trial, nifedipine was totally ineffective. Targeting the renin-angiotensin system seems a promising avenue in the treatment of this disease, and clinical trials should be carefully designed to re-evaluate the effectiveness of angiotensin I–converting enzyme inhibitors or angiotensin II receptor blockers in AR.
    Type of Medium: Online Resource
    ISSN: 1941-3289 , 1941-3297
    URL: Article
    DOI: 10.1161/CIRCHEARTFAILURE.108.801548
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
    detail.hit.zdb_id: 2428100-1
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