Key result
In rats with severe aortic regurgitation, moderate endurance training or carvedilol treatment partially normalized myocardial energy metabolism remodeling, including enzyme activities related to fatty acid oxidation and glycolysis.
Why the study?
Does endurance training or carvedilol improve myocardial energy metabolism in rats with chronic left ventricle volume overload from severe aortic regurgitation?
Does endurance training or carvedilol improve myocardial energy metabolism in rats with chronic left ventricle volume overload from severe aortic regurgitation?
Endurance training and beta-blockade with carvedilol can partially reverse the abnormal myocardial energy metabolism remodeling seen in chronic left ventricular volume overload from severe aortic regurgitation in a rat model.
Hypothesis-generating in rat aortic regurgitation; leaves open translation to human volume overload.
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.
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Lachance et al. (2014) studied Experimental chronic left ventricle volume overload (aortic regurgitation) (n=218). Endurance training or carvedilol vs. Untreated aortic regurgitation rats and sham-operated rats was evaluated on Myocardial energy metabolism (enzyme activities and gene expression). In rats with severe aortic regurgitation, moderate endurance training or carvedilol treatment partially normalized myocardial energy metabolism remodeling, including enzyme activities related to fatty acid oxidation and glycolysis.
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