Buonincontri Guido, Wood Nigel I, Puttick Simon G, Ward Alex O, Carpenter T Adrian, Sawiak Stephen J, Morton A Jennifer
Wolfson Brain Imaging Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK, CB2 0QQ.
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge, UK, CB2 3DY.
J Huntingtons Dis. 2014;3(1):25-32. doi: 10.3233/JHD-130083.
Increasingly, evidence from studies in both animal models and patients suggests that cardiovascular dysfunction is important in HD. Previous studies measuring function of the left ventricle (LV) in the R6/2 model have found a clear cardiac abnormality, albeit with preserved LV systolic function. It was hypothesized that an impairment of RV function might play a role in this condition via mechanisms of ventricular interdependence.
To investigate RV function in the R6/2 mouse model of Huntington's disease (HD).
Cardiac cine-magnetic resonance imaging (MRI) was used to determine functional parameters in R6/2 mice. In a first experiment, these parameters were derived longitudinally to determine deterioration of cardiac function with disease progression. A second experiment compared the response to a stress test (using dobutamine) of wildtype and early-symptomatic R6/2 mice.
There was progressive deterioration of RV systolic function with age in R6/2 mice. Furthermore, beta-adrenergic stimulation with dobutamine revealed RV dysfunction in R6/2 mice before any overt symptoms of the disease were apparent.
This work adds to accumulating evidence of cardiovascular dysfunction in R6/2 mice, describing for the first time the involvement of the right ventricle. Cardiovascular dysfunction should be considered, both when treatment strategies are being designed, and when searching for biomarkers for HD.
越来越多来自动物模型和患者研究的证据表明，心血管功能障碍在亨廷顿舞蹈病（HD）中很重要。先前在R6/2模型中测量左心室（LV）功能的研究发现了明显的心脏异常，尽管左心室收缩功能得以保留。据推测，右心室（RV）功能受损可能通过心室相互依存机制在这种情况下发挥作用。
研究亨廷顿舞蹈病（HD）R6/2小鼠模型中的右心室功能。
采用心脏电影磁共振成像（MRI）来测定R6/2小鼠的功能参数。在第一个实验中，纵向获取这些参数以确定随着疾病进展心脏功能的恶化情况。第二个实验比较了野生型和早期有症状的R6/2小鼠对应激试验（使用多巴酚丁胺）的反应。
R6/2小鼠的右心室收缩功能随年龄增长而逐渐恶化。此外，在疾病的任何明显症状出现之前，用多巴酚丁胺进行β-肾上腺素能刺激就显示出R6/2小鼠存在右心室功能障碍。
这项研究进一步证明了R6/2小鼠存在心血管功能障碍，首次描述了右心室的受累情况。在设计治疗策略以及寻找HD生物标志物时，都应考虑心血管功能障碍。
