SYMPATHOADRENAL AND CATECHOLAMINE FUNCTION IN HEALTH

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Catecholamine systems, operating at the interface between the mind and the body, exemplify three ways the brain regulates homeostasis -- via neurotransmitters (norepinephrine, NE), hormones (epinephrine, EPI), and autocrine/paracrine factors (dopamine, DA). We conducted clinical investigations in neurocardiology, catecholamine neurochemistry, and novel catecholaminergic systems. 6-[18F]fluorodopamine ([18F]-6F- DA) positron-emission tomographic (PET) scanning led to a new pathophysiological classification of primary chronic autonomic failure. Patients with pure autonomic failure (PAF) or parkinsonism and autonomic failure had cardiac sympathetic denervation, whereas patients with the Shy-Drager syndrome had decreased post-ganglionic sympathetic neural outflows to intact nerve terminals. 13N-ammonia and [18F]-6F-DA PET scanning detected perfusion or sympathoneural abnormalities in the affected limbs of patients with sympathetic dystrophy (RSD). Patients with a history of repeated episodes of neurocardiogenic syncope had decreased cardiac NE spillover, and patients with hypertrophic cardiomyopathy (HCM) had evidence for decreased neuronal uptake of NE in the hypertrophic myocardium. Neurochemical studies linked specific catecholaminergic phenotypes with genotypic abnormalities in Menkes' disease, familial dysautonomia (FD), and L-aromatic-amino-acid decarboxylase (LAAAD) deficiency. Treatment with L-DOPA as a dopaminergic pro-drug produced beneficial natriuretic responses in patients with congestive heart failure. Plasma DA-sulfate levels were found to depend on dietary factors and on production of endogenous DA in the gastrointestinal tract.