Background-Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary familial heart muscle disease associated with substantial cardiovascular morbidity and risk of sudden death. Efforts to discern relevant pathophysiological mechanisms have been impaired by lack of a suitable animal model. Methods and Results-ARVC was diagnosed in 23 boxer dogs (12 male; 9.1Ϯ2.3 years old). Clinical events alone or in combination included sudden death (nϭ9; 39%), ventricular arrhythmias of suspected right ventricular (RV) origin (nϭ19; 83%), syncope (nϭ12, 52%), and heart failure (nϭ3; 13%). Right ventricular enlargement or aneurysms occurred in 10 (43%). Striking histopathological abnormalities were present in each boxer dog but not in controls, including severe RV myocyte loss with replacement by fatty (nϭ15, 65%) or fibrofatty (nϭ8, 35%) tissue. Focal fibrofatty lesions were also present in both atria (nϭ8) and the left ventricle (LV) (nϭ11). Fatty replacement occupied substantially greater RV wall area in ARVC dogs than controls (40.4Ϯ18.8% versus 13.8Ϯ3.4%, respectively) (PϽ0.001); residual myocardium was correspondingly reduced (56.6Ϯ19.2% versus 84.8Ϯ3.8% in controls) (PϽ0.001). MRI demonstrated bright anterolateral and/or infundibular RV myocardial signals, confirmed as fat by histopathology. Myocarditis appeared in the RV (nϭ14, 61%) and LV (nϭ16, 70%) and in each dog with sudden death, but not in controls. Familial transmission was evident in 10 of the 23. Key Words: models, animal Ⅲ cardiomyopathy Ⅲ pathology Ⅲ death, sudden A rrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary familial cardiomyopathy associated with substantial cardiovascular morbidity and sudden death in the young. 1-3 ARVC is transmitted as an autosomal dominant trait, and 2 mutations have been identified at the cardiac ryanodine receptor 2 gene (ARVD2) and the desmoplakin gene (ARVD8). 4,5 It has been noted for many years that the boxer canine breed is predisposed to ventricular arrhythmias and sudden death, 6,7 but the underlying disease responsible for these clinical features has been incompletely defined. In light of advances in genomic mapping of the domestic dog, 8 a spontaneous canine model of ARVC and sudden death would provide a unique opportunity to study this disease genome and contribute valuable insights into its pathogenesis. Therefore, the purpose of the present study was to define the clinical and pathological features of a naturally occurring myocardial disease in boxer dogs and assess its suitability as an animal model of ARVC.
Conclusions-We
Methods
Selection of Animal SubjectsAs part of an ongoing study to evaluate the heritability of ventricular arrhythmias in boxer dogs, 239 such animals, including 6 large families, were prospectively recruited for Holter ECG between 1997 and 1999 at the Ohio State University College of Veterinary Medicine. Of those with substantial ectopy or syncope that died or were euthanized, 23 boxer dogs (12 male, 11 female) had autopsy examination and constitute the study group....