Autonomic Dysregulation in a Mouse Model of Muscular Dystrophy Destined to Develop Dilated Cardiomyopathy

Abstract

Mutations in the dystrophin‐glycoprotein complex cause muscular dystrophy and dilated cardiomyopathy (DCM) in animals and humans. Mice deficient in sarcoglycan delta (Sgcd), a component of this complex, develop muscular dystrophy at a young age (<10 wks) with later onset of DCM (Cell 98:465‐474,1999). We hypothesized that autonomic dysregulation may occur early in the disease progression before development of DCM. We measured cardiac function (echocardiography); blood pressure (BP) and heart rate (HR) (telemetry); and indices of autonomic regulation including baroreflex sensitivity (BRS) and HR variability (HRV‐SD) in 10‐12 wk old Sgcd‐/‐ and control C57BL/6 mice. Left ventricular ejection fraction (0.83±0.01 vs. 0.85±0.03) and end‐diastolic volume (26±2 vs. 33±4 µl) were normal in Sgcd‐/‐ mice. Histopathological features of muscular dystrophy were evident in skeletal muscle but not in the heart of Sgcd‐/‐ mice. Compared with control mice, Sgcd‐/‐ mice exhibited less locomotor activity (4±1 vs. 11±1 c/min), lower mean BP (100±2 vs.120±4 mmHg), and reductions in diurnal (night‐day) variability, BRS and HRV‐SD (see Table, *P<0.05).We conclude that young Sgcd‐/‐ mice exhibit decreased BP, loss of diurnal cardiovascular rhythms, and severe autonomic dysregulation prior to onset of cardiac dysfunction. We speculate that this early autonomic dysregulation may hasten the progression to DCM. (VA)