The online version of this article (doi:10.1186/1471-2261-14-190) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
DL performed two of the animal studies and analyzed the data (Figures 1, 2, 4 and Additional file 1: Figure S1). WD performed the additional animal study and analyzed the data (Figure 3). MCD contributed to the animals studies and performed part of the tissue analysis (Figures 3 and 7). ER performed the experiments leading to Figures 6 and 8. SG and OS performed the micro-PET study. JAR and RL supervised the micro-PET study. MA and JC designed and coordinated the entire study and wrote the manuscript. All authors read and approved the final manuscript.
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.
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.
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.
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.
Additional file 1: Supplemental methods and data. This file contains more detailed methods for the enzymatic assays as well as references. In addition, Figure S1. is a complement of data for the carvedilol study of Figures 7 and 8 in the manuscript. (PDF 227 KB)
Allard MF, Wambolt RB, Longnus SL, Grist M, Lydell CP, Parsons HL, Rodrigues B, Hall JL, Stanley WC, Bondy GP: Hypertrophied rat hearts are less responsive to the metabolic and functional effects of insulin. Am J Physiol Endocrinol Metab. 2000, 279: E487-E493. PubMed
Alaoui-Talibi Z, Guendouz A, Moravec M, Moravec J: Control of oxidative metabolism in volume-overloaded rat hearts: effect of propionyl-L-carnitine. Am J Physiol. 1997, 272: H1615-H1624. PubMed
Alaoui-Talibi Z, Landormy S, Loireau A, Moravec J: Fatty acid oxidation and mechanical performance of volume-overloaded rat hearts. Am J Physiol. 1992, 262: H1068-H1074. PubMed
Gibbs CL, Wendt IR, Kotsanas G, Young IR: Mechanical, energetic, and biochemical changes in long-term volume overload of rabbit heart. Am J Physiol. 1992, 262: H819-H827. PubMed
Bonow RO, Carabello BA, Kanu C, de Leon AC, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS, Smith SC, Jacobs AK, Adams CD, Anderson JL, Antman EM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Page RL, Riegel B: ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation. 2006, 114: e84-e231. 10.1161/CIRCULATIONAHA.106.176857. CrossRefPubMed
Zendaoui A, Lachance D, Roussel E, Couet J, Arsenault M: Usefulness of spironolactone in the treatment of chronic aortic valve regurgitation. J Heart Valve Dis. 2012, 21: 478-486. PubMed
Arsenault M, Zendaoui A, Roussel E, Drolet MC, Dhahri W, Grenier A, Gascon S, Sarrhini O, Rousseau JA, Lecomte R, Couet J: Angiotensin II converting enzyme inhibition improves survival, ventricular remodeling and myocardial energetics in experimental aortic regurgitation. Circ Heart Fail. 2013, 6: 1021-1028. 10.1161/CIRCHEARTFAILURE.112.000045. CrossRefPubMed
Lachance D, Plante E, Bouchard-Thomassin AA, Champetier S, Roussel E, Drolet MC, Arsenault M, Couet J: Moderate exercise training improves survival and ventricular remodeling in an animal model of left ventricular volume overload. Circ Heart Fail. 2009, 2: 437-445. 10.1161/CIRCHEARTFAILURE.108.845487. CrossRefPubMed
Dhahri W, Roussel E, Drolet MC, Gascon S, Sarrhini O, Rousseau JA, Lecomte R, Couet J, Arsenault M: Metformin reduces left ventricular eccentric re-modeling in experimental volume overload in the rat. J Clin Exp Cardiol. 2012, 13: 8-
Arsenault M, Plante E, Drolet MC, Couet J: Experimental aortic regurgitation in rats under echocardiographic guidance. J Heart Valve Dis. 2002, 11: 128-134. PubMed
Ménard SL, Ci X, Frisch F, Normand-Lauzière F, Cadorette J, Ouellet R, Van Lier JE, Bénard F, Bentourkia M, Lecomte R, Carpentier AC: Mechanism of reduced myocardial glucose utilization during acute hypertriglyceridemia in rats. Mol Imaging Biol. 2009, 11: 6-14. 10.1007/s11307-008-0171-2. CrossRefPubMed
Ménard SL, Croteau E, Sarrhini O, Gélinas R, Brassard P, Ouellet R, Bentourkia M, van Lier JE, Des Rosiers C, Lecomte R, Carpentier AC: Abnormal in vivo myocardial energy substrate uptake in diet-induced type 2 diabetic cardiomyopathy in rats. Am J Physiol Endocrinol Metab. 2010, 298: E1049-E1057. 10.1152/ajpendo.00560.2009. CrossRefPubMed
Croteau E, Bénard F, Cadorette J, Gauthier ME, Aliaga A, Bentourkia M, Lecomte R: Quantitative gated PET for the assessment of left ventricular function in small animals. J Nucl Med. 2003, 44: 1655-1661. PubMed
Croteau E, Gascon S, Bentourkia M, Langlois R, Rousseau JA, Lecomte R, Bénard F: [ 11C]Acetate rest–stress protocol to assess myocardial perfusion and oxygen consumption reserve in a model of congestive heart failure in rats. Nucl Med Biol. 2012, 39: 287-294. 10.1016/j.nucmedbio.2011.07.010. CrossRefPubMed
Champetier S, Bojmehrani A, Beaudoin J, Lachance D, Plante E, Roussel E, Couet J, Arsenault M: Gene profiling of left ventricle eccentric hypertrophy in aortic regurgitation in rats: rationale for targeting the beta-adrenergic and renin-angiotensin systems. Am J Physiol Heart Circ Physiol. 2009, 296: H669-H677. 10.1152/ajpheart.01046.2008. CrossRefPubMed
McMullen JR, Amirahmadi F, Woodcock EA, Schinke-Braun M, Bouwman RD, Hewitt KA, Mollica JP, Zhang L, Zhang Y, Shioi T, Buerger A, Izumo S, Jay PY, Jennings GL: Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy. Proc Natl Acad Sci U S A. 2007, 104: 612-617. 10.1073/pnas.0606663104. CrossRefPubMedPubMedCentral
- Endurance training or beta-blockade can partially block the energy metabolism remodeling taking place in experimental chronic left ventricle volume overload
Jacques A Rousseau
- BioMed Central
Neu im Fachgebiet Kardiologie
Mail Icon II