We conducted patient-oriented clinical research in neurocardiology. Studies focused on elucidating pathophysiologic mechanisms and developing novel diagnostic approaches for diseases of brain regulation of the cardiovascular system. These conditions often result from dysfunction of the autonomic nervous system (dysautonomia) or abnormally decreased or increased production of the catecholamines, norepinephrine (NE), epinephrine (EPI), or dopamine (DA). Patients with autonomic failure in the setting of Parkinsons disease all had cardiac sympathetic denervation, detected both by 6-[18F]fluorodopamine positron-emission tomographic scanning and by release of NE into the cardiac venous drainage during right heart catheterization. In contrast, patients with the Shy-Drager syndrome all had evidence for intact cardiac sympathetic nerve terminals. Results of the neurochemical, neuroimaging, and neuropharmacological approches agreed perfectly, supporting their usefulness in the differential diagnosis of these clinically similar syndromes. Patients with reflex sympathetic dystrophy (RSD, also called Complex Regional Pain Syndrome Type I) did not have consistently altered sympathetic innervation in the affected limb, although a minority of patients appeared to have either partially decreased sympathetic nerve traffic or decreased terminal innervation; most patients did not have sympathetically maintained pain. The sources and physiological significance of DA sulfate, the main form of DA in human plasma, were elucidated for the first time. Plasma DA sulfate in humans was found to derive mainly from metabolism of DA in the gastrointestinal tract. This finding is consistent with the concept of a gut-blood barrier for detoxifying ingested catecholamines and for delimiting actions of endogenous DA in a non-neuronal third catecholamine system. In normal volunteers, decreased skin temperature increased plasma NE levels selectively, whereas acute deprivation of the key metabolic fuel, glucose, evoked relatively selective increases in plasma EPI levels, supporting the notion of different central and peripheral neurochemical signatures for different stressors. In patients with a familial predisposition to pheochromocytoma, a clinically important tumor that produces catecholamines, measurements of plasma levels of metanephrines, metabolites of NE and EPI made in the tumor, provided a uniquely and virtually perfectly sensitive diagnostic test. - Sympathetic Catecholamines Stress Norepinephrine Epinephrine Dopamine Dysautonomia Autonomic Parkinson Pheochromocytoma - Human Subjects
Showing the most recent 10 out of 125 publications
