Pour savoir comment effectuer et gérer un dépôt de document, consultez le « Guide abrégé – Dépôt de documents » sur le site Web de la Bibliothèque. Pour toute question, écrivez à corpus@ulaval.ca.
 

Personne :
Lachance, Dominic.

En cours de chargement...
Photo de profil

Adresse électronique

Date de naissance

Projets de recherche

Structures organisationnelles

Fonction

Nom de famille

Lachance

Prénom

Dominic.

Affiliation

Département de Médecine expérimentale, Faculté de Médecine, Université Laval

ISNI

ORCID

Identifiant Canadiana

person.page.name

Résultats de recherche

Voici les éléments 1 - 10 sur 12
  • 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
    Effects of exercise in volume overload : insights from a model of aortic regurgitation
    (Lippincott Williams & Wilkins, 2009-06-01) Lachance, Dominic.; Roussel, Élise; Couët, Jacques; Bouchard Thomassin, Andrée-Anne; Champetier, Serge.; Plante, Éric; Arsenault, Marie
    Background : Aortic valve regurgitation (AR) imposes a pathologic volume overload to the left ventricle (LV), whereas aerobic exercise causes physiologic volume overloading. The impact of combining both LV volume overloads (pathologic and physiologic) is unknown. Considering the known beneficial effects of aerobic training on the cardiovascular system, we hypothesized that the positive effects would outweigh the negative ones and that exercise would improve the tolerance of the LV to AR. Methods : Forty female adult Wistar rats were randomly divided in the following groups: 1) sham sedentary (SS), 2) sham trained (ST), 3) AR sedentary (ARS), and 4) AR trained (ART). Training consisted in treadmill running for 30 min five times per week at 20 m·s−1 for 24wk. In vivo follow-up was made by echocardiography and invasive intracardiac pressure measurements. Hearts were harvested for tissue analysis. Results : Echocardiography revealed less LV dilation and hypertrophy in ART versus ARS as well as improved myocardial performance index. LV ejection fractions remained similar and within normal range in ART versus ARS. Invasive cardiac pressures yielded improved dP/dt− in ART versus ARS but similar dP/dt+. β1-Adrenergic receptor mRNA expression was improved in the ART group versus ARS. Conclusion : Our data suggest that a moderate aerobic exercise program helps minimize LV dilation and hypertrophy and improves diastolic cardiac performance in heart submitted to chronic volume overload due to severe aortic valve regurgitation in this animal model.
  • 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
    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
    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.
  • PublicationAccès libre
    Gender differences in left ventricular remodeling in chronic severe aortic valve regurgitation in rats.
    (Hertfordshire : ICR, 2006-05-03) Lachance, Dominic.; Roussel, Élise; Couët, Jacques; Drolet, Marie-Claude.; Plante, Éric; Arsenault, Marie
    BACKGROUND AND AIM OF THE STUDY: Aortic valve regurgitation (AR) can result in heart failure from chronic overloading of the left ventricle. As little is known of gender-specific responses of the left ventricle to this condition, the study aim was to compare left ventricular (LV) remodeling in male and female rats with severe AR. In order to assess the impact of estrogens on LV remodeling in AR, the effect of ovariectomy (OVX) was also evaluated. METHODS: AR was created in adult Wistar rats (females (control or OVX) and males). Animals were followed for 26 weeks and compared to sham-operated groups. Heart function was evaluated in vivo using echocardiography, and the hearts were subsequently harvested for tissue analysis. RESULTS: The LV ejection fraction was decreased similarly in both sexes. Despite similar echocardiographic AR severity, females had higher indexed cardiac output and the largest increase in LV weight, cardiomyocyte hypertrophy and eccentric remodeling. No differences were observed between control and OVX females. Ovariectomy had no significant impact on any of the parameters monitored. CONCLUSION: Female rats developed more LV remodeling in response to chronic AR than males. AR appears to impose a greater LV workload on females due to their smaller body and heart size. Hormonal status did not have any impact on LV remodeling in this experimental model.
  • PublicationAccès libre
    Endurance training or beta-blockade can partially block the energy metabolism remodeling taking place in experimental chronic left ventricle volume overload.
    (BioMed Central, 2014-12-17) Lachance, Dominic.; Roussel, Élise; Dhahri, Wahiba; Drolet, Marie-Claude.; Gascon, Suzanne; Arsenault, Marie; Sarrhini, Otman; Rousseau, Jacques A.; Lecomte, Roger
    BACKGROUND: Patients with chronic aortic valve regurgitation (AR) causing left ventricular (LV) volume overload can remain asymptomatic for many years despite having a severely dilated heart. The sudden development of heart failure is not well understood but alterations of myocardial energy metabolism may be contributive. We studied the evolution of LV energy metabolism in experimental AR. METHODS: LV glucose utilization was evaluated in vivo by positron emission tomography (microPET) scanning of 6-month AR rats. Sham-operated or AR rats (n = 10-30 animals/group) were evaluated 3, 6 or 9 months post-surgery. We also tested treatment intervention in order to evaluate their impact on metabolism. AR rats (20 animals) were trained on a treadmill 5 times a week for 9 months and another group of rats received a beta-blockade treatment (carvedilol) for 6 months. RESULTS: MicroPET revealed an abnormal increase in glucose consumption in the LV free wall of AR rats at 6 months. On the other hand, fatty acid beta-oxidation was significantly reduced compared to sham control rats 6 months post AR induction. A significant decrease in citrate synthase and complex 1 activity suggested that mitochondrial oxidative phosphorylation was also affected maybe as soon as 3 months post-AR.Moderate intensity endurance training starting 2 weeks post-AR was able to partially normalize the activity of various myocardial enzymes implicated in energy metabolism. The same was true for the AR rats treated with carvedilol (30 mg/kg/d). Responses to these interventions were different at the level of gene expression. We measured mRNA levels of a number of genes implicated in the transport of energy substrates and we observed that training did not reverse the general down-regulation of these genes in AR rats whereas carvedilol normalized the expression of most of them. CONCLUSION: This study shows that myocardial energy metabolism remodeling taking place in the dilated left ventricle submitted to severe volume overload from AR can be partially avoided by exercise or beta-blockade in rats.
  • PublicationAccès libre
    Transcriptional changes associated with long-term left ventricle volume overload in rats : impact on enzymes related to myocardial energy metabolism.
    (Hindawi, 2015-10-25) Lachance, Dominic.; Roussel, Élise; Couët, Jacques; Walsh-Wilkinson, Élisabeth; Dhahri, Wahiba; Gascon, Suzanne; Drolet, Marie-Claude.; Sarrhini, Otman; Arsenault, Marie; Rousseau, Jacques A.; Lecomte, Roger
    Patients with left ventricle (LV) volume overload (VO) remain in a compensated state for many years although severe dilation is present. The myocardial capacity to fulfill its energetic demand may delay decompensation. We performed a gene expression profile, a model of chronic VO in rat LV with severe aortic valve regurgitation (AR) for 9 months, and focused on the study of genes associated with myocardial energetics. Methods. LV gene expression profile was performed in rats after 9 months of AR and compared to sham-operated controls. LV glucose and fatty acid (FA) uptake was also evaluated in vivo by positron emission tomography in 8-week AR rats treated or not with fenofibrate, an activator of FA oxidation (FAO). Results. Many LV genes associated with mitochondrial function and metabolism were downregulated in AR rats. FA β-oxidation capacity was significantly impaired as early as two weeks after AR. Treatment with fenofibrate, a PPARα agonist, normalized both FA and glucose uptake while reducing LV dilation caused by AR. Conclusion. Myocardial energy substrate preference is affected early in the evolution of LV-VO cardiomyopathy. Maintaining a relatively normal FA utilization in the myocardium could translate into less glucose uptake and possibly lesser LV remodeling.
  • PublicationAccès libre
    Impact of anesthesia on echocardiographic evaluation of systolic and diastolic function in rats
    (Elsevier, 2006-11-28) Lachance, Dominic.; Roussel, Élise; Couët, Jacques; Drolet, Marie-Claude.; Plante, Éric; Arsenault, Marie
    Background : Echocardiography is used on rats but general anesthesia is usually necessary to be able to obtain a good quality echocardiogram. Each type of anesthetic agent has specific impacts on hemodynamics and, therefore, may affect differentially the echocardiographic measurements. Objectives : We sought to compare the echocardiograms of normal rats and rats with chronic aortic regurgitation under anesthesia using ketamine-xylazine or isoflurane. Methods : Animals underwent an echocardiogram with both drugs sequentially. Echocardiographic measurements were compared. Results : Mitral diastolic Doppler measurements (early diastolic filling wave [E] and late atrial diastolic filling wave [A] velocities) were significantly affected by the type of anesthesia in the normal group but not left ventricular dimensions or ejection fraction. Left ventricular dimensions were affected by the type of anesthesia in the aortic regurgitation group and diastolic Doppler flow. Conclusion : The anesthetic agent has significant specific impacts on many echocardiographic measurements. Investigators working with rat models should be aware of those potential effects.
  • PublicationAccès libre
    Effectiveness of β-blockade in experimental chronic aortic regurgitation
    (American Heart Association, 2004-09-13) Lachance, Dominic.; Roussel, Élise; Couët, Jacques; Drolet, Marie-Claude.; Gaudreau, Martin.; Plante, Éric; Arsenault, Marie
    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 β1-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.