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

Lachance D, Dhahri W, Drolet MC, Roussel É, Gascon S, Sarrhini O, Rousseau JA, Lecomte R, Arsenault M, Couet J - BMC Cardiovasc Disord (2014)

Bottom Line: 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.Responses to these interventions were different at the level of gene expression.

View Article: PubMed Central - PubMed

Affiliation: Groupe de recherche sur les valvulopathies, Centre de Recherche, Institut Universitaire de cardiologie et de pneumologie de Québec, Université Laval, 2725, Chemin Sainte-Foy, Québec City, Québec G1V 4G5, Canada. jacques.couet@med.ulaval.ca.

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.

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Related in: MedlinePlus

Moderate endurance training (tr) helps normalize activity levels of enzymes implicated in the LV energy metabolism in 9-month AR rats. Indexed (i) heart weight was corrected for the tibial length. HADH (hydroxyacyl-Coenzyme A dehydrogenase), HK (hexokinase) PFK (phosphofructokinase), citrate synthase (CS) and complex 1 enzymatic activities were measured in LV homogenates as described in the Methods. Results are expressed as mean ± SEM (n = 10/group) in μmoles/min/mg of tissue. *p < 0.05, **p < 0.01 and ***p < 0.001 between sham and AR and ¶p < 0.05 between AR and AR-tr groups.
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Fig5: Moderate endurance training (tr) helps normalize activity levels of enzymes implicated in the LV energy metabolism in 9-month AR rats. Indexed (i) heart weight was corrected for the tibial length. HADH (hydroxyacyl-Coenzyme A dehydrogenase), HK (hexokinase) PFK (phosphofructokinase), citrate synthase (CS) and complex 1 enzymatic activities were measured in LV homogenates as described in the Methods. Results are expressed as mean ± SEM (n = 10/group) in μmoles/min/mg of tissue. *p < 0.05, **p < 0.01 and ***p < 0.001 between sham and AR and ¶p < 0.05 between AR and AR-tr groups.

Mentions: In order to evaluate if some alterations of the myocardial energy metabolism could be reversed, we tested the impact of moderate endurance training we previously showed to improve the condition of chronic AR rats. AR rats were thus submitted to moderate intensity endurance training on a treadmill (up to 20 m/s for 30 minutes) for a period of 9 months. Of the 20 animals, 14 survived the entire protocol. As illustrated in Figure 5, endurance training did not reduce the heart hypertrophy in AR animals although a trend was observed. Levels of enzymatic activity were normalized for the HADH, CPT, PFK and CS suggesting an improvement of the myocardial metabolic profile associated with exercise.Figure 5


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

Lachance D, Dhahri W, Drolet MC, Roussel É, Gascon S, Sarrhini O, Rousseau JA, Lecomte R, Arsenault M, Couet J - BMC Cardiovasc Disord (2014)

Moderate endurance training (tr) helps normalize activity levels of enzymes implicated in the LV energy metabolism in 9-month AR rats. Indexed (i) heart weight was corrected for the tibial length. HADH (hydroxyacyl-Coenzyme A dehydrogenase), HK (hexokinase) PFK (phosphofructokinase), citrate synthase (CS) and complex 1 enzymatic activities were measured in LV homogenates as described in the Methods. Results are expressed as mean ± SEM (n = 10/group) in μmoles/min/mg of tissue. *p < 0.05, **p < 0.01 and ***p < 0.001 between sham and AR and ¶p < 0.05 between AR and AR-tr groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4279960&req=5

Fig5: Moderate endurance training (tr) helps normalize activity levels of enzymes implicated in the LV energy metabolism in 9-month AR rats. Indexed (i) heart weight was corrected for the tibial length. HADH (hydroxyacyl-Coenzyme A dehydrogenase), HK (hexokinase) PFK (phosphofructokinase), citrate synthase (CS) and complex 1 enzymatic activities were measured in LV homogenates as described in the Methods. Results are expressed as mean ± SEM (n = 10/group) in μmoles/min/mg of tissue. *p < 0.05, **p < 0.01 and ***p < 0.001 between sham and AR and ¶p < 0.05 between AR and AR-tr groups.
Mentions: In order to evaluate if some alterations of the myocardial energy metabolism could be reversed, we tested the impact of moderate endurance training we previously showed to improve the condition of chronic AR rats. AR rats were thus submitted to moderate intensity endurance training on a treadmill (up to 20 m/s for 30 minutes) for a period of 9 months. Of the 20 animals, 14 survived the entire protocol. As illustrated in Figure 5, endurance training did not reduce the heart hypertrophy in AR animals although a trend was observed. Levels of enzymatic activity were normalized for the HADH, CPT, PFK and CS suggesting an improvement of the myocardial metabolic profile associated with exercise.Figure 5

Bottom Line: 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.Responses to these interventions were different at the level of gene expression.

View Article: PubMed Central - PubMed

Affiliation: Groupe de recherche sur les valvulopathies, Centre de Recherche, Institut Universitaire de cardiologie et de pneumologie de Québec, Université Laval, 2725, Chemin Sainte-Foy, Québec City, Québec G1V 4G5, Canada. jacques.couet@med.ulaval.ca.

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.

Show MeSH
Related in: MedlinePlus