This program project aims to improve understanding of the pathogenesis and treatment of autonomic failure. To achieve this goal, a series of closely integrated, highly focussed projects are proposed. We will compare the restricted autonomic neuropathy of the postural tachycardia syndrome (POTS) with the severe generalized autonomic disorders (multiple system atrophy [MSA], pure autonomic failure [PAF], and the autonomic neuropathies) to define the natural history, pathogenetic mechanisms, and treatment strategies (Project 1: Low). These goals are uniquely achievable at Mayo since we have a large cohort of patients with POTS and generalized autonomic failure whose disorders have been well characterized using quantitative tests of known sensitivity and specificity. Closely integrated with Project 1 is Project 3 (Joyner), which will use microneurographic techniques to directly measure sympathetic traffic to skeletal muscle in POTS and vasovagal syncope and directly measure venous and arterial pressures in response to graded lower body negative pressure (to apportion the rules of cardiopulmonary and arterial baroreceptors). This project will also test the novel hypothesis that vasovagal syncope is due to active vasodilatation, mediated by nitric oxide. We will test the hypothesis that autonomic failure is MSA is significantly due to a depletion of medullary catecholamine- and neuropeptide-containing neurons known to be involved in visceral control. Immunocytochemical labeling of tyrosine hydroxylase (TH), neuropeptide Y (NPY), and substance P (sP), and histochemical reaction of nitric oxide synthase containing neurons will be used for the morphometric studies (Project 2: Benarroch). Finally, we have, for the first time, reliable models of preganglionic and postganglionic autonomic failure. By applying similar pharmacologic and morphometric techniques and questions to the human and experimentally models, we are uniquely situated to relate and evaluate postulated mechanisms in MSA and PAF (Projects 1-3) with these models (Project 4: Brimijoin). Taken together, this program will seriously begin to address a major public health problem of autonomic failure.
| Limberg, Jacqueline K; Johnson, Blair D; Holbein, Walter W et al. (2016) Interindividual variability in the dose-specific effect of dopamine on carotid chemoreceptor sensitivity to hypoxia. J Appl Physiol (1985) 120:138-47 |
| Figueroa, Juan J; Singer, Wolfgang; Sandroni, Paola et al. (2015) Effects of patient-controlled abdominal compression on standing systolic blood pressure in adults with orthostatic hypotension. Arch Phys Med Rehabil 96:505-10 |
| Wehrwein, Erica A; Limberg, Jacqueline K; Taylor, Jennifer L et al. (2015) Effect of bilateral carotid body resection on the counterregulatory response to hypoglycaemia in humans. Exp Physiol 100:69-78 |
| Moffett, Kristin; Crosson, Bruce; Spence, Jeffrey S et al. (2015) Word-finding impairment in veterans of the 1991 Persian Gulf War. Brain Cogn 98:65-73 |
| Bharucha, Adil E; Kudva, Yogish; Basu, Ananda et al. (2015) Relationship between glycemic control and gastric emptying in poorly controlled type 2 diabetes. Clin Gastroenterol Hepatol 13:466-476.e1 |
| Limberg, Jacqueline K; Farni, Kathryn E; Taylor, Jennifer L et al. (2014) Autonomic control during acute hypoglycemia in type 1 diabetes mellitus. Clin Auton Res 24:275-83 |
| Limberg, Jacqueline K; Taylor, Jennifer L; Dube, Simmi et al. (2014) Role of the carotid body chemoreceptors in baroreflex control of blood pressure during hypoglycaemia in humans. Exp Physiol 99:640-50 |
| Figueroa, Juan J; Singer, Wolfgang; Parsaik, Ajay et al. (2014) Multiple system atrophy: prognostic indicators of survival. Mov Disord 29:1151-7 |
| Singer, Wolfgang; Sletten, David M; Opfer-Gehrking, Tonette L et al. (2012) Postural tachycardia in children and adolescents: what is abnormal? J Pediatr 160:222-6 |
| Kimpinski, Kurt; Figueroa, Juan J; Singer, Wolfgang et al. (2012) A prospective, 1-year follow-up study of postural tachycardia syndrome. Mayo Clin Proc 87:746-52 |
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