Parasympathetic but not sympathetic cardiac dysfunction at early stages of Parkinson's disease

Autonomic cardiovascular dysfunction is common in Parkinson's disease (PD). Imaging studies suggest loss of cardiac sympathetic nerves even in the absence of clinical signs of autonomic dysfunction. Aim of the study was to investigate the functional significance of autonomic cardiovascular denervation at early stages of PD. Seven PD patients (Hoehn and Yahr class 1 or 1.5) without clinical signs of autonomic dysfunction and seven age-matched healthy control subjects were studied. To evaluate the pre- and post-synaptic components of sympathetic innervation, dose-response curves of isoproterenol (no neuronal uptake) and epinephrine (neuronal uptake) on heart rate, contractility, cardiac output and systemic vascular resistance were determined echocardiographically. Additionally, measurements of baroreflex sensitivity and 24-h heart rate variability were done. The chronotropic and inotropic responses during stimulation with isoproterenol and epinephrine were similar in PD patients and control subjects. Assessment of baroreflex sensitivity yielded no difference. Of the parameters of 24-h heart rate variability, only measures of high-frequency heart rate variation that more purely reflect parasympathetic activity were significantly depressed in PD patients as compared with control subjects. The results of our study using direct determination of catecholamine-mediated chronotropic and contractile responses provide evidence against a functionally relevant sympathetic dysfunction. Possibly, sympathetic denervation is incomplete and the remaining fibers are sufficient for the maintenance of autonomic control. In contrast, the depression of several parameters of heart rate variability supports a significant change of parasympathetic activity at an early stage of PD with subclinical autonomic failure.