Right Ventricular Dysfunction in the R6/2 Transgenic Mouse Model of Huntington's Disease is Unmasked by Dobutamine
| Autor: | A. Jennifer Morton, Stephen J. Sawiak, Simon Puttick, Nigel I. Wood, Alexander O. Ward, T. Adrian Carpenter, Guido Buonincontri |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cardiac function curve
medicine.medical_specialty Heart malformation Ventricular Dysfunction Right Magnetic Resonance Imaging Cine Mice Transgenic Article Mice Cellular and Molecular Neuroscience Huntington's disease Dobutamine Internal medicine Animals Medicine Longitudinal Studies Sympathomimetics medicine.diagnostic_test business.industry Stroke Volume Magnetic resonance imaging Stroke volume medicine.disease Cardiac Imaging Techniques Disease Models Animal Huntington Disease medicine.anatomical_structure Ventricle Heart failure Disease Progression Cardiology Neurology (clinical) business medicine.drug |
| Zdroj: | Journal of Huntington's Disease. 3:25-32 |
| ISSN: | 1879-6397 |
| DOI: | 10.3233/jhd-130083 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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