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Drolet, Marie-Claude.

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Drolet

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Marie-Claude.

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Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval

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Voici les éléments 1 - 10 sur 28
  • PublicationAccès libre
    Moderate exercise training improves survival and ventricular remodeling in an animal model of left ventricular volume overload.
    (Lippincott Williams & Wilkins, 2009-09-15) Lachance, Dominic.; Roussel, Élise; Couët, Jacques; Champetier, Serge.; Drolet, Marie-Claude.; Plante, Éric; Arsenault, Marie
    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. CONCLUSIONS: 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.
  • PublicationAccès libre
    Early left ventricular remodeling in acute severe aortic regurgitation : insights from an animal model.
    (Hertfordshire : ICR, 2008-05-03) Lachance, Dominic.; Roussel, Élise; Couët, Jacques; Drolet, Marie-Claude.; Plante, Éric; Arsenault, Marie
    BACKGROUND AND AIM OF THE STUDY: Chronic aortic regurgitation (AR) induces left ventricular (LV) hypertrophy and eventually LV dysfunction. While the effects of chronic AR on the left ventricle are well known, the effects of acute AR have not been adequately evaluated. It was hypothesized that the LV tissues would be rapidly remodeled by acute AR, and that the renin-angiotensin system would be involved in that acute remodeling. METHOD: The early LV adaptations to acute AR were evaluated serially over a period of 14 days, using a rat model. Adaptations were evaluated in vivo by echocardiography, and in vitro on explanted heart tissue after one, two, or 14 days. RESULTS: After 14 days, the left ventricle of AR rats was already significantly hypertrophied and dilated (end-diastolic diameter +16% (p <0.05) versus sham; LV mass +16% (p <0.01) versus sham). A short and transient increase in fractional shortening was observed during the first 48 h after AR induction. The cardiomyocyte cross-sectional area and perivascular fibrosis were significantly increased after 14 days of AR. The number of fibronectin-positive cells in LV sections rapidly increased, as did the fibronectin protein and mRNA content of LV crude homogenates. The expression of pro-matrix metalloproteinase 2 was clearly abnormal after two days. Significant shifts in the expression of angiotensin II receptors were also detected as early as one 1 day. CONCLUSION: Significant macroscopic and microscopic abnormalities were present in the left ventricle of rats with acute AR, soon after its induction. Considerable hypertrophy, perivascular fibrosis and extracellular matrix (ECM) remodeling were present after only 14 days. These results suggest that, in AR, the myocytes and ECM are affected significantly at a very early stage of the disease.
  • PublicationAccès libre
    Interstitial cells from left-sided heart valves display more calcification potential than right-sided ones : an in vitro study of porcine valves
    (ICR, 2009-07-01) Roussel, Élise; Couët, Jacques; Drolet, Marie-Claude.; Bouchard Martel, Joanie; Arsenault, Marie
    BACKGROUND AND AIM OF THE STUDY: The calcification of cardiac valves is more frequently observed on left-sided (aortic or mitral) than right-sided (pulmonic or tricuspid) valves. The cause of this preferential left-sided calcification remains relatively unknown. The study aim was to evaluate the capacity of interstitial cells isolated from the four cardiac valves of healthy adult pigs to calcify in culture. METHODS: Interstitial cells were isolated from the valve leaflets of three healthy young pigs and cultured in DMEM/fetal bovine serum (10%) in the presence or absence of osteogenic additives (ascorbic acid, dexamethasone, beta-glycerophosphate). RESULTS: The proliferation rate was similar for cells from each of the four valves. After longer periods of culture (> 10 days), cells from each valve spontaneously formed several calcification nodules, the process being accelerated in the presence of osteogenic additives (to 4-7 days). Alkaline phosphatase (AP) activity was highest in cells originating from the aortic and mitral valves, respectively, and least in those from the pulmonic and tricuspid valves. Culture with the osteogenic additives increased the AP activity by at least 50% for each valve, but the relative AP activity between cells from each valve origin tended to remain similar (aortic > mitral > pulmonic > tricuspid). Interestingly, the levels of matrix Gla-protein mRNA (an endogenous calcification inhibitor) followed an opposite trend of expression for each valve. CONCLUSION: Interstitial cells from porcine cardiac valves share similarities, although the capacity to calcify is more evident in cells from valves of the left side of the heart. Interstitial cells from the aortic valve displayed the greatest potential for calcification.
  • PublicationRestreint
    Angiotensin-converting enzyme inhibitor captopril prevents volume overload cardiomyopathy in experimental chronic aortic valve regurgitation
    (National Research Council of Canada., 2004-03-12) Lachance, Dominic.; Roussel, Élise; Gauthier, Cindy; Couët, Jacques; Lapointe, Évelyne; Drolet, Marie-Claude.; Gaudreau, Martin.; Plante, Éric; Arsenault, Marie
    L'efficacité des inhibiteurs de l'enzyme de conversion de l'angiotensine I (IECA) dans le traitement de l'insuffisance aortique (IA) chronique est encore mal comprise et controversée. Les mécanismes par lesquels les IECA ont un effet protecteur dans la surcharge de volume du ventricule gauche (VG) sont encore peu clairs et les études cliniques ont jusqu'à maintenant donné des résultats contradictoires. Dans cette étude, nous avons cherché à comparer l'efficacité de deux doses différentes d'un IECA (captopril) dans un modèle animal d'IA chronique. Chez des rats Wistar ayant une IA sévère, nous avons étudié les effets d'un traitement de 6 mois avec une faible dose de captopril (FD; 25 mg/kg) ou une haute dose (HD; 75 mg/kg) sur la fonction et l'hypertrophie du VG. Les rats IA témoins ont tous développé une hypertrophie excentrique du VG ainsi qu'une dysfonction systolique. Le traitement FD n'a pu prévenir l'hypertrophie et n'a procuré qu'une protection modeste contre la dysfonction systolique. Le traitement HD a préservé la fonction systolique et a eu tendance à ralentir le développement de l'hypertrophie du VG. L'index cardiaque est demeuré élevé et similaire pour chacun des groupes traités ou non. L'activité du système rénine–angiotensine (SRA) a aussi été étudiée. L'activité de l'ECA a augmenté dans les VGs des animaux IA et le traitement HD a fortement abaissé l'expression des ARNm encodant les différents récepteurs à l'angiotensine II dans ce tissu. L'expression de la fibronectine a augmenté dans les VG des animaux IA mais le traitement HD a presque complètement renversé cet effet de l'IA. L'inhibiteur de l'ECA captopril s'est avéré efficace à haute dose dans notre modèle d'IA. Cette efficacité pourrait être liée à une modulation du SRA tissulaire et de la fibrose dans le VG.
  • PublicationAccès libre
    Dobutamine stress echocardiography in healthy adult male rats
    (BioMed Central, 2005-10-26) Lachance, Dominic.; Roussel, Élise; Couët, Jacques; Drolet, Marie-Claude.; Plante, Éric; Arsenault, Marie
    Background : 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.
  • PublicationAccès libre
    Multiple short-chain dehydrogenases/reductases are regulated in pathological cardiac hypertrophy.
    (Elsevier, 2018-08-13) Roussel, Élise; Couët, Jacques; Boire-Lavigne, Anne-Marie; Drolet, Marie-Claude.; Arsenault, Marie
    Cardiac hypertrophy (CH) is an important and independent predictor of morbidity and mortality. Through expression profiling, we recently identified a subset of genes (Dhrs7c, Decr, Dhrs11, Dhrs4, Hsd11b1, Hsd17b10, Hsd17b8, Blvrb, Pecr), all of which are members of the short-chain dehydrogenase/reductase (SDR) superfamily and are highly expressed in the heart, which were significantly dysregulated in a rat model of CH caused by severe aortic valve regurgitation (AR). Here, we studied their expression in various models of CH, as well as factors influencing their regulation. Among the nine SDR genes studied, all but Hsd11b1 were downregulated in CH models (AR rats or mice infused with either isoproterenol or angiotensin II). This regulation showed a clear sex dimorphism, being more evident in males than in females irrespective of CH levels. In neonatal rat cardiomyocytes, we observed that treatment with the alpha-1 adrenergic receptor agonist, phenylephrine, mostly reproduced the observations made in CH animals models. Retinoic acid, on the other hand, stimulated the expression of most of the SDR genes studied, suggesting that their expression may be related to cardiomyocyte differentiation. Indeed, levels of expression were found to be higher in the hearts of adult animals than in neonatal cardiomyocytes. In conclusion, we identified a group of genes modulated in animal models of CH and mostly in males. This could be related to the activation of the fetal gene expression program in pathological CH situations, in which these highly expressed genes are down-regulated in the adult heart.
  • PublicationAccès libre
    Development of aortic valve sclerosis or stenosis in rabbits : role of cholesterol and calcium
    (ICR, 2008-07-01) Couët, Jacques; Drolet, Marie-Claude.; Arsenault, Marie
    BACKGROUND AND AIM OF THE STUDY: Aortic valve sclerosis is fairly common and is currently seen as a marker of systemic atherosclerosis. For unclear reasons only a minority of those sclerotic valves will evolve to become stenotic suggesting that atherogenic factors alone are insufficient to explain the development of valve stenosis. We had reported in a model of cholesterol fed rabbits that a combination of high cholesterol with vitamin D supplementation was necessary to induce valve stenosis and significant calcium deposition whereas high cholesterol alone only induced a sclerosis of the valve. In this study, we further evaluated the role of vitamin D treatment in the development of aortic valve disease (sclerosis or stenosis) in this rabbit model. METHODS: Rabbits were divided in 4 groups followed for 12 weeks: 1) no treatment; 2) cholesterol-enriched diet, 3) cholesterol-enriched diet + vitamin D2 (VD; 50000IU, daily) 4) VD alone for 12 weeks. Echocardiographic assessment of the aortic valve was done at baseline, and every 4 weeks thereafter. Aortic valve area, maximal and mean transvalvular gradients were recorded and compared over time. Immunohistological study of the valves of AS rabbits was also realized for several classical atherosclerosis markers. RESULTS: Vitamin D2 treated animal did not develop any stenosis of the valve despite increased echogenicity due to diffuse calcium deposits on the leaflets without any atherosclerotic lesions. Only the combination of high cholesterol with VD resulted in a decrease of aortic valve area. Immunohistological analysis of aortic valves from VD rabbits showed the presence of calcium deposits, T-cell infiltration in addition to positive labeling for alpha-smooth muscle cell actin. We did not observe macrophage infiltration in aortic valve leaflets of VD rabbits. CONCLUSION: Hypercholesterolemia or vitamin D supplements alone could not induce aortic valve stenosis in our animal model whereas the combination resulted in a decreased aortic valve area. These findings support the hypothesis that a combination of atherosclerotic and calcifying factors is necessary to induce aortic valve stenosis in this model.
  • PublicationAccès libre
    Experimental aortic valve stenosis in rabbits
    (Elsevier Biomedical, 2003-03-29) Couët, Jacques; Drolet, Marie-Claude.; Arsenault, Marie
    Objectives : We studied a known rabbit model of atherosclerosis to assess the effect of a hypercholesterolemic diet on aortic valve morphology and function. We also evaluated the effects of the combination of this diet with vitamin D supplements on the development of the disease and the occurrence of valve calcification. Background : Aortic valve stenosis (AVS) is the most common valvular heart disease. Recent observations have suggested a link between atherosclerosis and the development of AVS. However, until now, there has been no solid direct proof of this potential link. Methods : Rabbits were divided in three groups: 1) no treatment; 2) cholesterol-enriched diet (0.5% cholesterol); and 3) cholesterol-enriched diet plus vitamin D2(50,000 IU/day). Echocardiographic assessment of the aortic valve was done at baseline and after 12 weeks of treatment. The aortic valve area (AVA) and maximal and mean transvalvular gradients were recorded and compared over time. Results Control animals displayed no abnormalities of the aortic valve. Despite important increases in blood total cholesterol levels, animals in group 2 did not develop any significant functional aortic valve abnormality over 12 weeks. However, eight of 10 of the animals in group 3 developed a significant decrease in AVA (p = 0.004) and significant increases in transvalvular gradients (p = 0.003). Conclusions : This study supports a potential link between atherosclerosis and the development of AVS. The differences noted between hypercholesterolemic animals with or without vitamin D2supplementation imply a significant role of calcium in the development of AVS, meriting further attention.
  • PublicationAccès libre
    Angiotensin II converting enzyme inhibition improves survival, ventricular remodeling and myocardial energetics in experimental aortic regurgitation.
    (Lippincott Williams & Wilkins, 2013-09-17) Roussel, Élise; Couët, Jacques; Grenier, Audrey; Zendaoui, Adnane; Dhahri, Wahiba; Drolet, Marie-Claude.; Gascon, Suzanne; Arsenault, Marie; Sarrhini, Otman; Rousseau, Jacques A.; Lecomte, Roger
    Background— Aortic valve regurgitation (AR) is a volume-overload disease causing severe eccentric left ventricular (LV) hypertrophy and eventually heart failure. There is currently no approved drug to treat patients with AR. Many vasodilators including angiotensin-converting enzyme inhibitors have been evaluated in clinical trials, but although some results were promising, others were inconclusive. Overall, no drug has yet been able to improve clinical outcome in AR and the controversy remains. We have previously shown in an animal model that captopril (Cpt) reduced LV hypertrophy and protected LV systolic function, but we had not evaluated the clinical outcome. This protocol was designed to evaluate the effects of a long-term Cpt treatment on survival in the same animal model of severe aortic valve regurgitation. Methods and Results—Forty Wistar rats with AR were treated or untreated with Cpt (1 g/L in drinking water) for a period of 7 months to evaluate survival, myocardial remodeling, and function by echocardiography as well as myocardial metabolism by µ positron emission tomography scan. Survival was significantly improved in Cpt-treated animals with a survival benefit visible as soon as after 4 months of treatment. Cpt reduced LV dilatation and LV hypertrophy. It also significantly improved the myocardial metabolic profile by restoring the level of fatty acids metabolic enzymes and use. Conclusions—In a controlled animal model of pure severe aortic valve regurgitation, Cpt treatment reduced LV remodeling and LV hypertrophy and improved myocardial metabolic profile and survival. These results support the need to reevaluate the role of angiotensin-converting enzyme inhibitors in humans with AR in a large, carefully designed prospective clinical trial.
  • PublicationAccès libre
    Treatment of combined aortic regurgitation and systemic hypertension : insights from an animal model study.
    (Oxford University Press, 2006-08-01) Lachance, Dominic.; Roussel, Élise; Couët, Jacques; Drolet, Marie-Claude.; Gaudreau, Martin.; Plante, Éric; Arsenault, Marie
    Background : Hypertension (HT) and aortic valve regurgitation (AR) often coexist but the specific impacts of AR + HT on the left ventricle (LV) are still unknown. The best treatment strategy for this combination of diseases is also unclear. The objectives of this study were 1) to evaluate LV function, remodeling and 2) to assess the effects of the angiotensin-converting enzyme (ACE) inhibitor captopril (C) in rats with AR ± HT in spontaneously hypertensive rats (SHR). Methods : Animals were grouped as follows: normotensive (NT) Wistar-Kyoto, NT + AR, hypertensive SHR (HT), and HT + AR receiving or not captopril (150 mg/kg/d). Hearts were evaluated in vivo by echocardiography and harvested for tissue analysis after 6 months of evolution. Results : The HT + AR rats had the worst LV hypertrophy (LVH), subendocardial fibrosis, and lowest ejection fraction. Captopril normalized BP in HT and HT + AR, but could not prevent LVH in HT + AR as well as it did in isolated HT. The LV ejection fraction remained below normal in HT + AR + captopril compared to HT alone + captopril. Cardiomyocyte hypertrophy remained in HT + AR + captopril but was normalized in HT + captopril. Subendocardial fibrosis was reduced by captopril in HT + AR. Conclusions : The AR + HT rats had the most severe myocardial abnormalities. High dose captopril was effective to slow LVH and preserve normal LV ejection fraction in isolated HT or AR, but was less effective when both pathologies were combined. Prohypertrophic stimuli clearly remain active in HT + AR despite ACE inhibition. These results suggest that a very aggressive medical treatment strategy may be required to optimize LV protection when AR and HT co-exist.