We conducted patient-oriented research in clinical neurocardiology. Studies focused on etiology, diagnosis, pathophysiology, and treatment of diseases and disorders involving the catecholamines norepinephrine (NE), adrenaline (ADR), or dopamine (DA). Patient groups had primary chronic autonomic failure (Parkinson disease (PD), pure autonomic failure, or multiple system atrophy); chronic orthostatic intolerance (postural tachycardia syndrome or neurocardiogenic syncope), or pheochromocytoma, a clinically important tumor that produces catecholamines. Patients with familial PD from mutation of the gene encoding alpha-synuclein or from excessive expression of the normal gene had a loss of cardiac sympathetic nerves, indicating that in PD dysautonomia can reflect alpha-synucleinopathy. Patients with PD and orthostatic hypotension (OH) had poor baroreflexive regulation of the sympathetic nervous system and loss of sympathetic nerves in the heart, confirming PD+OH as not only a movement disorder but also a form of dysautonomia. Treatment with L-dihydroxphenylserine improved OH in patients with chronic autonomic failure; the improvement probably resulted from conversion of the drug to NE in neuronal and non-neuronal cells outside the brain. Results of a cardiac catheterization study supported the concept of cardiac sympathetic hyperactivity in postural tachycardia syndrome. In a new protocol the efficacy of non-selective beta-adrenoceptor blockade is being assessed in preventing tilt-induced neurocardiogenic syncope. Plasma levels of metanephrines, metabolites of NE and ADR, continue to provide a virtually perfectly sensitive screening test for pheochromocytoma. A large prospective study confirmed the validity of 6-[18F]fluorodopamine positron-emission tomographic scanning for diagnostic localization of pheochromocytoma. Microarray studies have indicated several gene expression changes that help explain the different clinical and neurochemical phenotypes of inherited pheochromocytomas.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Intramural Research (Z01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
United States
Zip Code
Goldstein, David S; Eisenhofer, Graeme; Kopin, Irwin J (2006) Clinical catecholamine neurochemistry: a legacy of Julius Axelrod. Cell Mol Neurobiol 26:695-702
Sharabi, Yehonatan; Eldadah, Basil; Li, Sheng-Ting et al. (2006) Neuropharmacologic distinction of neurogenic orthostatic hypotension syndromes. Clin Neuropharmacol 29:97-105
Gamboa, Alfredo; Gamboa, Jorge L; Holmes, Courtney et al. (2006) Plasma catecholamines and blood volume in native Andeans during hypoxia and normoxia. Clin Auton Res 16:40-5
Goldstein, David S (2006) Orthostatic hypotension as an early finding in Parkinson's disease. Clin Auton Res 16:46-54
Li, Sheng-Ting; Eldadah, Basil A; Sharabi, Yehonatan et al. (2006) Coronary vascular resistance in primary chronic autonomic failure. Clin Auton Res 16:293-5
Eldadah, Basil A; Pechnik, Sandra L; Holmes, Courtney S et al. (2006) Failure of propranolol to prevent tilt-evoked systemic vasodilatation, adrenaline release and neurocardiogenic syncope. Clin Sci (Lond) 111:209-16
Petersson, Magnus; Friberg, Peter; Eisenhofer, Graeme et al. (2005) Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure. Eur Heart J 26:906-13
Lenders, Jacques W M; Eisenhofer, Graeme; Mannelli, Massimo et al. (2005) Phaeochromocytoma. Lancet 366:665-75
Pacak, K; Ilias, I; Adams, K T et al. (2005) Biochemical diagnosis, localization and management of pheochromocytoma: focus on multiple endocrine neoplasia type 2 in relation to other hereditary syndromes and sporadic forms of the tumour. J Intern Med 257:60-8
Tipre, Dnyanesh N; Goldstein, David S (2005) Cardiac and extracardiac sympathetic denervation in Parkinson's disease with orthostatic hypotension and in pure autonomic failure. J Nucl Med 46:1775-81

Showing the most recent 10 out of 125 publications