Affiliations: Wolfson Brain Imaging Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK | Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge, UK | Behavioural and Clinical Neuroscience Institute, Department of Experimental Psychology, University of Cambridge, Downing Site, Cambridge, UK
Note:  Correspondence to: A. Jennifer Morton, Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge, CB2 3DY, UK. E-mail: [email protected]
Abstract: Background: 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 mouse 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. Objective: To investigate RV function in the R6/2 mouse model of Huntington's disease (HD). Methods: 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. Results: 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. Conclusions: 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.
Keywords: MRI, right ventricle, cognitive function, heart failure, Huntington's Disease