title: 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Dominic
authors.initials: D
authors.lastname: Lachance
authors.forename: Wahiba
authors.initials: W
authors.lastname: Dhahri
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Drolet
authors.forename: Élise
authors.initials: É
authors.lastname: Roussel
authors.forename: Suzanne
authors.initials: S
authors.lastname: Gascon
authors.forename: Otman
authors.initials: O
authors.lastname: Sarrhini
authors.forename: Jacques A
authors.initials: JA
authors.lastname: Rousseau
authors.forename: Roger
authors.initials: R
authors.lastname: Lecomte
authors.forename: Marie
authors.initials: M
authors.lastname: Arsenault
authors.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.
authors.forename: Jacques
authors.initials: J
authors.lastname: Couet
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001022:Aortic Valve Insufficiency / Q000000981:diagnostic imaging / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010805:Physical Conditioning, Animal; D010807:Physical Endurance; D017208:Rats, Wistar; D014463:Ultrasonography
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D005947:Glucose