• Brimijoin, W. Stephen (PI)
  • Brimijoin, William (PI)
  • Brimijoin, W. Stephen (PI)
  • White, Robert (PI)
  • Brimijoin, William (PI)
  • Vernino, Steven (PI)
  • Benarroch, Eduardo (PI)
  • Brimijoin, William Stephen (PI)

Project: Research project

Project Details


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.
Effective start/end date9/15/837/31/10


  • Medicine(all)
  • Neuroscience(all)