Lachance Dominic, Dhahri Wahiba, Drolet Marie-Claude, Roussel Élise, Gascon Suzanne, Sarrhini Otman, Rousseau Jacques A, Lecomte Roger, Arsenault Marie, Couet Jacques
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.
BMC Cardiovasc Disord. 2014 Dec 17;14:190. doi: 10.1186/1471-2261-14-190.
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.
慢性主动脉瓣反流（AR）导致左心室（LV）容量超负荷的患者，尽管心脏已严重扩张，但多年来可能仍无症状。心力衰竭的突然发生机制尚不清楚，但心肌能量代谢的改变可能起了作用。我们研究了实验性AR中左心室能量代谢的演变。
通过对6个月龄AR大鼠进行正电子发射断层扫描（microPET），在体内评估左心室葡萄糖利用情况。对假手术或AR大鼠（每组n = 10 - 30只动物）在术后3、6或9个月进行评估。我们还测试了治疗干预措施，以评估它们对代谢的影响。20只AR大鼠每周在跑步机上训练5次，持续9个月，另一组大鼠接受β受体阻滞剂治疗（卡维地洛）6个月。
MicroPET显示，6个月时AR大鼠左心室游离壁的葡萄糖消耗异常增加。另一方面，与假手术对照大鼠相比，AR诱导6个月后脂肪酸β氧化显著降低。柠檬酸合酶和复合物1活性的显著降低表明，线粒体氧化磷酸化可能在AR后3个月就受到了影响。AR后2周开始的中等强度耐力训练能够部分使参与能量代谢的各种心肌酶的活性恢复正常。用卡维地洛（30 mg/kg/d）治疗的AR大鼠也是如此。这些干预措施在基因表达水平上的反应不同。我们测量了许多与能量底物转运相关基因的mRNA水平，观察到训练并没有逆转AR大鼠中这些基因的普遍下调，而卡维地洛使其中大多数基因的表达恢复正常。
本研究表明，在大鼠中，运动或β受体阻滞剂可部分避免因AR导致严重容量超负荷的扩张型左心室发生心肌能量代谢重塑。
