Dataset Information

Endurance training or beta-blockade can partially block the energy metabolism remodeling taking place in experimental chronic left ventricle volume overload.

ABSTRACT:

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.

SUBMITTER: Lachance D

PROVIDER: S-EPMC4279960 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Aortic valve regurgitation (AR) results in left ventricle (LV) volume overload (VO) leading to its dilation and hypertrophy (H). We study a rat model of severe AR induced by puncturing one or two leaflets using a catheter. Most of our studies were conducted in male animals. Recently, we started investigating if sex dimorphism existed in the AR rat model. We observed that AR females developed as much LVH as males but morphological remodeling differences were present. A head-to-head comparison of LV morphological and functional changes had never been performed in AR males (M) and females (F) using the latest modalities in cardiac imaging by echocardiography. METHODS:We performed a longitudinal study to evaluate the development of LV hypertrophy caused by chronic AR in male and female rats over 6?months. Sham-operated (sham) animals were used as controls. RESULTS:LV diastolic volumes (EDV) increased more over 6?months in sham males than in females (38% vs. 23% for EDV, both p?<?0.01). AR resulted in significant LV dilation for both sexes (54% vs. 51% increase in EDV) vs. baseline values. Since normal cardiac growth was less in females, dilation from AR was relatively more important for them (88% (M) vs. 157% (F) increase in EDV over sham). AR caused LV wall thickening in both males and females. It happened sooner for AR females and was more important than in males (25% (M) vs. 56% (F) increase in septum thickness at 2?months and 10% (M) vs. 30% (F) at 6?months). We then evaluated if AR was associated with changes in LV strain using speckle-tracking 2D echocardiography. Global longitudinal strain remained similar between AR and sham animals. Circumferential strain was negatively modulated by AR but only in females and early after VO induction (13% (M) vs. 26% (F)). CONCLUSION:AR resulted in more LV dilation and quicker wall thickening in female AR rats compared to males. Global circumferential strain was negatively modulated in AR females but not in males. AR also seemed to lead to a more spherical LV shape in females whereas; it kept mostly an ellipsoid shape in males. This can influence validity of mass estimation of the dilated LV in females by echocardiography.