ABSTRACTS 23rd INTERNATIONAL SYMPOSIUM ON THE AUTONOMIC NERVOUS SYSTEM Atlantis Resort, Paradise Island, Bahamas October 31–November 3, 2012 Preliminary Program

1. Clin Auton Res (2012) 22:207–258
DOI 10.1007/s10286-012-0175-5
ABSTRACTS
23rd INTERNATIONAL SYMPOSIUM ON THE AUTONOMIC
NERVOUS SYSTEM
Atlantis Resort
Paradise Island, Bahamas
October 31–November 3, 2012
Preliminary Program
WEDNESDAY, OCTOBER 31, 2012
6:00–7:00 PM Registration
Imperial Foyer South I
7:00–7:15 PM Welcome—Dr. Michael Joyner, President
Imperial Ballroom CD
Autonomic Failure: PAF, MSA, Parkinson’s Disease
Chairs: Eduardo Benarroch & Steven Vernino
7:15–7:30 PM Alpha synuclein as a cutaneous biomarker of Parkinson disease
C.H. Gibbons, N. Wang, J. Lafo, R. Freeman
Boston, MA, USA
7:30–7:45 PM CSF biomarkers of central and peripheral catecholamine deficiency in synucleinopathies
D.S. Goldstein, L. Sewell, C. Holmes, C. Sims-O’Neil, Y. Sharabi
Bethesda, MD, USA
7:45–8:00 PM Prognostic indicators and clinical spectrum of MSA based on autopsy-confirmed cases
J.J. Figueroa, A.K. Parsaik, W. Singer, P. Sandroni, E.E. Benarroch, P.A. Low, J.H. Bower
Rochester, MN, USA
8:00–8:15 PM Mechanical stimulation of the feet improves gait and increases cardiac vagal profile in Parkinson’s disease
F. Barbic, M. Galli, M. Canesi, A. Porta, V. Cimolin, V. Bari, L. Dalla Vecchia, F. Dipaola, V. Pacetti, F. Meda,
I. Bianchi, E. Brunetta, R. Furlan
Milan, Italy
8:15–8:30 PM Profound myocardial catecholamine depletion in Lewy body diseases
D.S. Goldstein, P. Sullivan, T. Jenkins, C. Holmes, M. Basile, D.C. Mash, I.J. Kopin, Y. Sharabi
Bethesda, MD, USA
8:30–8:45 PM Autonomic dysfunction in Parkinsonian LRRK2 mutation carriers
´
B. Tijero, J.C. Gomez Esteban, K. Berganzo, V. Llorens, H.J.J. Zarranz
Bilbau, Spain
8:45–9:00 PM Comparison of techniques for non-invasive assessment of systemic hemodynamics in autonomic function testing
C. Sims-O’Neil, S. Pechnik, L. Sewell, L. Nez, D.S. Goldstein
Bethesda, MD, USA
THURSDAY, NOVEMBER 1, 2012
7:30–8:00 AM Breakfast & Exhibits
Imperial Ballroom B
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8:00–8:45 AM Plenary Lecture
Master and commander: the brain and the autonomic nervous system
Vaughan G. Macefield, Ph.D
University of Western Sydney & Neuroscience Research Australia Sydney, Australia
Cerebral Blood Flow, Neuroimaging in Brain and Heart & Pediatric Autonomic Disorders
Chairs: Lucy Norcliffe-Kaufmann & Jens Tank
8:45–9:00 AM The middle cerebral artery dilates to sodium nitroprusside: a combined transcranial Doppler and near infrared
spectroscopy study
J.M Stewart, C.E. Schwartz, Z.R. Messer, C. Terilli, M.S. Medow,
Valhalla, NY, USA
9:00–9:15 AM Cerebral oxygenation, heart rate & blood pressure responses in congenital central hypoventilation syndrome (CCHS)
during exogenous ventilatory challenges: PHOX2B genotype/CCHS phenotype association
M.S. Carroll, P.P. Patwari, T.M. Stewart, C.D. Brogadir, A.S. Kenny, C.M. Rand, D.E. Weese-Mayer
Chicago, IL, USA
9:15–9:30 AM Time course of cardiac sympathetic denervation in Parkinson disease
D.S. Goldstein
Bethesda, MD, USA
9:30–9:45 AM Parental attribution of symptoms in adolescents with postural tachycardia syndrome and its relation to child
functioning and psychological variables
E.M. Keating, R.M. Antiel, K.E. Weiss, D. Wallace, P.R. Fischer, C. Harbeck-Weber
Rochester, MN, USA
9:45–10:00 AM Cardiovagal sensitivity and orthostatic heart rate response in young patients with orthostatic intolerance
W. Singer, A.K. Parsaik, E.E. Benarroch, P. Sandroni, P.A. Low
Rochester, MN, USA
10:00–10:15 AM Parental response to pain: the impact on functional disability, depression, anxiety, and pain acceptance in adolescents
with chronic pain and orthostatic intolerance
R.M. Antiel, E.M. Keating, K.E. Weiss, D.P. Wallace, P.R. Fischer, C. Harbeck-Weber
Rochester, MN, USA
10:15–10:30 AM Coffee Break
Imperial Ballroom B
Autonomic Regulation: Basic Science & Animal Studies
Chairs: David Jardine & Imad Jarjour
10:30–10:45 AM Relationship between ganglionic long-term potentiation (LTP) and homeostatic synaptic plasticity in experimental
autoimmune autonomic ganglionopathy (EAAG)
Z. Wang, S. Vernino
Dallas, TX, USA
10:45–11:00 AM Methionine sulfoxide reductase A: a novel molecular determinant of baroreflex sensitivity, blood pressure and
hypertensive end-organ damage
R. Sabharwal, R. El Accaoui, M.K. Davis, J.A. Goeken, R. Weiss, F.M. Abboud, D. Meyerholz, M.W. Chapleau
Iowa City, IA, USA
11:00–11:15 AM Baroreflex induced changes in stressed blood volume, not cardiac output curve, is the central mechanism preventing
volume load induced pulmonary edema
T. Sakamoto, T. Kakino, K. Sunagawa
Fukuoka, Japan
11:15–11:30 AM Prostaglandin D synthase is critical for development of chronic angiotensin II-salt hypertension in the rat
G.D. Fink, N. Asirvatham-Jeyaraj
East Lansing, MI, USA
11:30–11:45 AM The central chemoreflex activation induces sympathoexcitation and resets the arterial baroreflex without
compromising its pressure stabilizing function
K. Saku, K. Sunagawa
Fukuoka, Japan
11:45–12:00 PM Advanced techniques and pitfalls of autonomic function assessment and arrhythmia analysis in the mouse model
C.M. Welzig, J.B. Galper
Charleston, SC, USA
12:00–1:30 PM Lunch & Poster Session I
Imperial Ballroom B
1:30–3:30 PM Free Time
3:30–4:00 PM AAS Business meeting
Imperial Ballroom CD
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Awards Session
Chairs: Michael Joyner & Wouter Wieling
4:00–4:45 PM Streeten Lecture
The ‘‘ups and downs’’ of blood pressure & baroreflex sensitivity—a historical and personal perspective
Mark Chapleau, Ph.D
University of Iowa and Veterans Affairs Medical Center, Iowa City, IA, USA
4:45–5:00 PM Streeten Travel Fellowship Award
Blunted osmopressor response in familial dysautonomia
N. Goulding, L. Norcliffe-Kaufmann, J. Martinez, D. Roncevic, L. Stok, F. Axelrod, H. Kaufmann
New York, NY, USA
5:00–5:15 PM FMS/Penaz Wesseling Award
Paradox elevations in angiotensin II, independent of plasma renin activity, contribute to the supine hypertension of
primary autonomic failure
A.C. Arnold, L.E Okamoto, C. Shibao, A. Gamboa, S.R. Raj, D. Robertson, I. Biaggioni
Nashville, TN, USA
5:15–5:30 PM FMS/Penaz Wesseling Award
Chronic effects of aliskiren versus hydrochlorothiazide on sympathetic neural responses to head-up tilt in hypertensive
seniors
Y. Okada, S.S. Jarvis, S.A. Best, T.B. Bivens, R.L. Meier, B.D. Levine, Q. Fu
Dallas, TX, USA
5:30–5:45 PM AAS Travel Award
Association between cerebral autoregulation and white matter hyperintensities in elderly individuals
S. Purkayastha, B. Paccha, I. Iloputaife, D.K. Kiely, F.A. Sorond, L.A. Lipsitz
Roslindale, MA, USA
5:45–6:00 PM AAS Travel Award
The change in arterial stiffness during ganglionic blockade is associated with sympathetic nerve activity in women
J.N. Barnes, R.E. Harvey, E.C. Hart, N. Charkoudian, T.B. Curry, J.H. Eisenach, W.T. Nicholson, M.J. Joyner,
D.P. Casey
Rochester, MN, USA
FRIDAY, NOVEMBER 2, 2012
7:00–7:30 AM Breakfast & Exhibits
Imperial Ballroom B
7:30–8:15 AM Plenary Lecture
Autonomic responses to pregnancy
Qi Fu, M.D., Ph.D
Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, and UT Southwestern
Medical Center, Dallas, TX, USA
Microneurography & Cardiovascular Control in Humans/Cardiovascular Disease, Diabetes, Obesity & Aging
Chairs: Jill Barnes & Qi Fu
8:15–8:30 AM Catheter based renal nerve ablation does not elicit a central sympatholytic response in difficult to control hypertensive
patients
J. Brinkmann, K. Heusser, B.M. Schmidt, J. Menne, G. Klein, H. Haller, A. Diedrich, J. Jordan, J. Tank
Hanover, Germany
8:30–8:45 AM Methodological considerations for assessing resting spontaneous baroreflex control of muscle sympathetic nerve
activity in humans
S.W. Holwerda, H. Yang, J.R. Carter, P.J. Fadel
Columbia, MO, USA
8:45–9:00 AM Sleep deprivation augments cardiovascular reactivity to acute stress in humans
H. Yang, J.J. Durocher, R.A. Larson, J.P. DellaValla, J.R. Carter
Houghton, MI, USA
9:00–9:15 AM Susceptibility to inducible ventricular arrhythmia in type I diabetic Akita mice is dependent on abnormalities of Ca2+
handling
H. Jin, M. Rajab, M. Aronovitz, B. Wang, K. Picard, H. Park, M. Link, J.B. Galper
Boston, MA, USA
9:15–9:30 AM Sympathetic hyper-responsiveness In takotsubo cardiomyopathy
L. Norcliffe-Kaufmann, J. Martinez, H. Kaufmann, H. Reynolds
New York, NY, USA
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9:30–9:45 AM Improvement of obesity-associated insulin resistance during autonomic blockade
A. Gamboa, L. Okamoto, A. Arnold, S. Raj, A. Diedrich, N. Abumrad, I. Biaggioni
Nashville, TN, USA
9:45–11:15 AM Coffee & Poster Session II
Imperial Ballroom B
Postural Orthostatic Tachycardia Syndrome (POTS)
Chairs: Satish Raj & Wolfgang Singer
11:15–11:30 AM Beta-2 adrenergic receptor polymorphism and hemodynamics in patients with postural orthostatic tachycardia
syndrome and healthy controls
M.N. Manento, L.R. Gullixson, K.K. Nickander, P.A. Low, J.H. Eisenach
Rochester, MN, USA
11:30–11:45 AM The pathophysiology of neuropathic and non-neuropathic postural tachycardia syndrome
C. Gibbons, I. Bonyhay, A. Benson, R. Freeman
Boston, MA, USA
11:45–12:00 PM Deconditioning in patients with orthostatic intolerance
A. Parsaik, T.G. Allison, W. Singer, D.M. Sletten, M.J. Joyner, E.E. Benarroch, P.A. Low, P. Sandroni
Rochester, MN, USA
12:00–12:15 PM Preliminary data on the durability of improved symptoms, functioning, and psychological distress in adolescents with
POTS treated in a multidisciplinary treatment program
B.K. Bruce, T.E. Harrison, K.E. Weiss, P.R. Fischer, S.P. Ahrens, W.N. Timm
Rochester, MN, USA
12:15–12:30 PM Objective measures of sleep in patients with POTS
S.J. Kizilbash, P.R. Fischer, R.M. Lloyd
Rochester, MN, USA
12:30–12:45 PM Reduced alpha-adrenergic vascular response: the physiological link between postural orthostatic tachycardia
syndrome and neurally mediated syncope
N. Mehta, M. Tavora-Mehta, J.C. Guzman, C.A. Morillo
Hamilton, ON, Canada
12:45–7:00 PM Free Time
7:00–10:00 PM Presidential Dinner
Ripples Pool Deck
SATURDAY, NOVEMBER 3, 2012
7:30–8:00 AM Breakfast & Exhibits
Imperial Ballroom B
Diabetic, Autoimmune & Other Autonomic Neuropathies
Chairs: Christopher Gibbons & Christoph Schroeder
8:00–8:15 AM Multi-scale glycemic variability affects brain structure and functional outcomes in type 2 diabetes mellitus
X. Cui, A. Galica, B. Manor, A. Abduljalil, C.-K. Peng, V. Novak
Boston, MA, USA
8:15–8:30 AM The laser Doppler imaging axon-reflex flare area—a novel regression thresholding based technique to assess
neurovascular function
T. Siepmann, B.M. Illigens, R. Freeman, C. Gibbons
Boston, MA, USA
8:30–8:45 AM Long-term outcomes in autoimmune autonomic ganglionopathy
S. Muppidi, E.B. Spaeth, C. Gibbons, S. Vernino
Dallas, TX, USA
8:45–9:00 AM Type I diabetic Akita mice demonstrate decreased heart rate variability and increased inducibility of ventricular
tachycardia which are reversed by statins
C.M. Welzig, H.-J. Park, M. Rajab, M. Aronovitz, H. Jin, M.S. Link, J.B. Galper
Charlston, SC, USA
9:00–9:15 AM The quantification of sudomotor nerve fibers: a multicenter study in diabetes
C.H. Gibbons, J. Lafo, G. Smith, R. Singleton, R. Freeman
Boston, MA, USA
9:15–10:45 AM Coffee & Poster Session III
Imperial Ballroom B
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Orthostatic Hypotension and Syncope
Chairs: Rasna Sabharwal & Darren Casey
10:45–11:00 AM Treatment of neurogenic orthostatic hypotension (NOH) with droxidopa: results from a multicenter, double-blind,
randomized, placebo-controlled, parallel group, induction design study
H. Kaufmann, P. Low, I. Biaggioni, C.J. Mathias, R. Freeman, L.A. Hewitt
New York, NY, USA
11:00–11:15 AM What is MSNA doing at the onset of syncope?
D.L. Jardine
Christchurch, New Zealand
11:15–11:30 AM A meta-analysis of pharmacologic treatments of orthostatic hypotension
C.H. Gibbons, S. Raj
Boston, MA, USA
11:30–11:45 AM Increasing cardiac output does not change middle cerebral artery blood velocity in the hyperthermic human
C.G. Crandall, T. Seifert, T.E. Wilson, M. Bundgaard-Nielsen, N.H. Secher
Dallas, TX, USA
11:45–12:00 PM Patterns of diagnosis and intervention in neurogenic orthostatic hypotension (NOH): a patient-flow study
H. Kaufmann, R.E. Paquette
New York, NY, USA
12:00–12:30 PM Open Discussion & Adjourn
POSTER SESSION I
Thursday, November 1, 2012
12:00–1:30 PM
Autonomic Failure: PAF, MSA, Parkinson’s Disease
Poster #1 A randomized, double-blind, placebo-controlled clinical trial of Rifampicin in multiple system atrophy
P.A. Low, S. Gilman, D. Robertson, I. Biaggioni, W. Singer, H. Kaufmann, S. Perlman, W. Cheshire, S. Vernino,
R. Freeman, R.A. Hauser, S. Lessig
Rochester, MN, USA
Poster #2 Orthostatic hypotension in Parkinson disease: passive tilt vs. active standing
J. Martinez, J.C. Esteban Gomez, B. Tijero Merino, K. Berganzo, H. Kaufmann
New York, NY, USA
Poster #3 Cerebellar and parkinsonian phenotypes in multiple system atrophy (MSA). Similarities and differences
D. Roncevic, J. Martinez, L. Norcliffe-Kaufmann, H. Kaufmann
New York, NY, USA
Poster #4 A novel quantitative index of baroreflex-sympathoneural function: application to patients with chronic autonomic
failure
F. Rahman, D.S. Goldstein
Bethesda, MD, USA
Poster #5 Loss of cerebral blood flow rhythm in Parkinson’s disease and vascular parkinsonism
S.-J. Yeh, B.-W. Chang, B.-Y. Liau, C.-C. Chiu
Taichung, Taiwan
Pediatric Autonomic Disorders
Poster #6 Temperature profile in congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity with
hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): ibutton measures of
peripheral skin temperature
R. Saiyed, C.M. Rand, M.S. Carroll, P.P. Patwari, T. Stewart, C. Koliboski, D.E. Weese-Mayer
Chicago, IL, USA
Poster #7 Heart rate variability in hospitalized children: autonomic response to laughter and engagement
P.P. Patwari, M.S. Carroll, K. Gray, M.K. Janda, A.S. Kenny, T.H. Stewart, C. Brogadir, S.H. Wang, D.M. Steinhorn
Chicago, IL, USA
Poster #8 Cardiac stroke volume and sympathetic/parasympathetic measurements increase the sensitivity and specificity of
HUTT in children and adolescents
M.T. Numan, J.E. Lankford, A. Gourishankar, I.J. Butler
Houston, TX, USA
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Autonomic Regulation: Basic Science & Animal Studies
Poster #9 Biogenic amine metabolism in juvenile neurocardiogenic syncope with dysautonomia
I.J. Butler, J.E. Lankford, M.T. Numan
Houston, TX, USA
Poster #10 The iceman revisited: autonomic function tests during performance of the Asian Tummo meditation technique
J.T. Groothuis, M.T.E. Hopman
Nijmegen, The Netherlands
Poster #11 Evidence for central sensitization in bladder pain syndrome from the ICEPAC trial (Interstitial Cystitis: Elucidation
of Psychophysiologic and Autonomic Characteristics)—preliminary psychometric findings
J.W. Janata, F. Daneshgari, C.A.T. Buffington, G. Chelimsky, M.D. Louttit, D. Zhang, T.C. Chelimsky
Cleveland, OH, USA
Novel Therapies & Clinical Trials
Poster #12 The antiemetic efficacy of carbidopa: a randomized, double-blind, placebo-controlled crossover study in patients with
familial dysautonomia
L. Norcliffe-Kaufmann, J. Martinez, F. Axelrod, H. Kaufmann
New York, NY, USA
Poster #13 Comparative efficacy between the norepinephrine transporter blocker, atomoxetine, against midodrine for the
treatment of orthostatic hypotension
C.E. Ramirez, L.E. Okamoto, A. Gamboa, S.R. Raj, A. Diedrich, D. Robertson, I. Biaggioni, C. Shibao
Nashville, TN, USA
Poster #14 Beneficial effects of oral rehydration solution on orthostatic intolerance
M.S. Medow, D. Tewari, A. Aggarwal, Z. Messer, J.M. Stewart
Valhalla, NY, USA
Gastrointestinal & Urogenital Systems, IBS, Cystitis
Poster #15 Musculoskeletal evaluation of patients with interstitial cystitis
T.V. Sanses, G. Chelimsky, D. Zhang, J. Janata, T. Mahajan, B. Fenton, A. Askari, R. Elston, T. Chelimsky, ICEPAC
Study Group
Milwaukee, WI, USA
Poster #16 Heart rate variability in pelvic pain
P. Singh, J. Thayer, G. Chelimsky, T. Chelimsky
Milwaukee, WI, USA
Poster #17 Study of the P2X2 and 7 receptors in the enteric glial cells of ileum rat subjected to ischemia and reperfusion
C.E. Mendes, K. Palombit, W. Tavares de Lima, P. Castelucci
˜
Sao Paulo, Brazil
Poster #18 Brainstem neuropeptides and vagal protection of the gastric mucosal against injury: role of prostaglandins, nitric
oxide and calcitonin-gene related peptide in capsaicin afferents
Y. Tache
Los Angeles, CA, USA
Poster #19 Autonomic dysfunction and esophageal dysmotility in persons with spinal cord injury
G.J. Schilero, M. Radulovic, C. Renzi, C. Yen, W.A. Bauman, M. Korsten
Bronx, NY, USA
Poster #20 Real time change of prefrontal cortex activity related to normal and abnormal bladder filling in Parkinson disease:
a functional near-infrared spectroscopy (fNIRS) study
C. Yamaguchi, T. Uchiyama, T. Yamamoto, R. Sakakibara, M. Fuse, M. Yanagisawa, T. Kamai, T. Ichikawa,
K. Hirata, S. Kuwabara, T. Yamanishi
Tochigi, Japan
Poster #21 Effect of Brilliant Blue G on P2X7 receptor after intestinal ischemia and reperfusion
K. Palombit, C.E. Mendes, W. Tavares de Lima, P. Castelucci
Sao Paulo, Brazil
Poster #22 Photo-stimulating effects of low reactive level laser on bladder dysfunction in neurological disease rats
T. Uchiyama, C. Yamaguchi, T. Yamamoto, R. Sakakibara, M. Fuse, M. Yanagisawa, T. Kamai, T. Ichikawa,
K. Hirata, S. Kuwabara, T. Yamanishi
Tochigi, Japan
Cerebral Blood Flow Regulation
Poster #23 Cerebral blood flow in autonomic failure
L. Rivera Lara, P. Novak
Worcester, MA, USA
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Poster #24 Added clinical value of cerebral blood flow in juveniles and young adults with neurocardiogenic syncope and
dysautonomia as measured by near-infrared spectroscopy
J.E. Lankford, M.T. Numan, A. Gourishankar, I.J. Butler
Houston, TX, USA
POSTER SESSION II
Friday, November 2, 2012
9:45–11:15 AM
Microneurography & Cardiovascular Reflexes in Humans
Poster #25 Do the chronic heart failure patients have limited sympathetic response to a transient baroreflex stress?
P. Zubin Maslov, T. Breskovic, J.K. Shoemaker, Z. Dujic
Split, Croatia
Poster #26 Assessment of cardiovascular adrenergic function using the Valsalva maneuver—reproducibility and validity of
indices
T.L. Gehrking, J.A. Gehrking, J.D. Schmelzer, P.A. Low, W. Singer
Rochester, MN, USA
Poster #27 Sex differences in limb vascular reactivity to mental stress in humans
J.R. Carter, H. Yang, T.D. Drummer
Houghton, MI, USA
Poster #28 Melatonin does not alter skin sympathetic nerve responses to mental stress
C.A. Ray, C.L. Sauder, M.D. Muller
Hershey, PA, USA
Poster #29 The arterial baroreflex resets with orthostasis
C.E. Schwartz, J.M. Stewart
Hawthorne, NY, USA
Poster #30 Carotid chemoreflex and muscle metaboreflex interactions in humans
H. Edgell, M.K. Stickland
Edmonton, AB, Canada
Poster #31 Do multi-unit sympathetic discharge patterns change with age and cardiovascular disease?
D.N. Brewer, P. Zubin Maslov, Z. Dujic, J.K. Shoemaker
London, Ontario, Canada
Cardiovascular Disease, Obesity & Aging: Human Studies
Poster #32 Acute baroreflex sensitivity impairment due to insulin-induced experimental hypoglycemia
A. Rao, I. Bonyhay, S. Ballatori, G. Adler, R. Freeman
Boston, MA, USA
Poster #33 Autonomic contribution to blood pressure and resting energy expenditure in obese hispanics
L.E. Okamoto, C. Shibao, A. Gamboa, A. Diedrich, G. Farley, S. Paranjape, I. Biaggioni
Nashville, TN, USA
Poster #34 The impact of injury to autonomic pathways on cardiovascular disease risk after spinal cord injury
H.J.C. Ravensbergen, I.S. Sahota, S.A. Lear, V.E. Claydon
Burnaby, British Columbia, Canada
Poster #35 What is the best marker for obesity in individuals with spinal cord injury?
H.J.C. Ravensbergen, M.C. Keenleyside, S.A. Lear, V.E. Claydon
Burnaby, British Columbia, Canada
Poster #36 Central arterial stiffness and autonomic modulation in active women
P. Latchman, G. Gates, J. Pereira, R. Axtell, M. Bartels, R. De Meersman
New Haven, CT, USA
Poster #37 Impaired autonomic modulation in acute stroke improves with clinical recovery within 72 hours
M.J. Hilz, H. Marthol, S. Moeller, J. Koehn, A. Akhundova, P. De Fina, S. Schwab
Erlangen, Germany & New York, NY, USA
Poster #38 Relation of cardiovagal baroreflex sensitivity to impaired carotid artery elastic function in patients with tetralogy of
Fallot
A. Pinter, T. Horvath, A. Sarkozi, D. Cseh, M. Kollai
Budapest, Hungary
Poster #39 Features of vascular neurogenic regulation in patients with atrial fibrillation and heart failure
O.V. Mamontov, A.V. Kozlenok, E.R. Bernhard, E.V. Parmon, E.V. Shlyakhto
Saint-Petersburg, Russian Federation
Poster #40 Calcitonin gene related peptide level and endocannabinoid system activity in patients with abdominal obesity and
arterial hypertension
E. Shlyakhto, E. Bazhenova, O. Belyaeva, A. Berezina, O. Berkovich, E. Baranova
Saint-Petersburg, Russian Federation
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Poster #41 Heart rate variability and high sensitivity C-reactive protein: influence of coronary artery lesions
N.Y. Tamburus, V.C. Kunz, R.F.L. Paula, M.R. Salviati, T.A.G. Nery, E. da Silva
˜
Sao Paulo, Brazil
Sympathovagal Balance & Spectral Analysis
Poster #42 Oligofiber recordings detail single-fiber sympathetic nerve discharge
C.-K. Su, C.-H. Chiang, C.-M. Ho, C.-M. Lee, Y.-P. Fan
Taipei, Taiwan
Poster #43 Cardiovascular autonomic control in the first year after spinal cord injury
J. Inskip, M. McGrath, B. Kwon, V. Claydon
Burnaby, BC, Canada
Poster #44 ‘‘Sympathovagal balance’’—a thermodynamic perspective
R. Schondorf, J. Benoit, M.J. Lafitte
Montreal, QC, Canada
Poster #45 The autonomic testing of normal subjects
G. Chelimsky, S.M. Ialacci, T.C. Chelimsky
Milwaukee, WI, USA
Blood Flow & Autonomics
Poster #46 Alpha-adrenergic blockade unmasks a greater compensatory vasodilation in hypoperfused contracting muscle
D.P. Casey, M.J. Joyner
Rochester, MN, USA
Poster #47 COMPASS 31—a refined and abbreviated composite autonomic symptom score
D.M. Sletten, G.A. Suarez, P.A. Low, J. Mandrekar, W. Singer
Rochester, MN, USA
Poster #48 Autonomic, Blood Flow and Sensory Small Fiber Scale (ABSS)
P. Novak
Worcester, MA, USA
Poster #49 Systemic dysautonomia in complex regional pain syndrome—a feasibility study
K.R. Chemali, K. McNeeley, L. Zhou, T. Chelimsky
Norfolk, VA, USA
POSTER SESSION III
Saturday, November 3, 2012
9:15–10:45 AM
Exercise, Temperature Regulation & Hypoxia
Poster #50 Thermophysiological consequences of an absent evening melatonin release in spinal cord injury
H. Jones, J.T. Groothuis, T.M.H. Eijsvogels, J. Nyakayiru, R.J.M. Verheggen, A. Thompson, E.J.W. van Someren, G.
Atkinson, M.T.E. Hopman, D.H.J. Thijssen
Nijmegen, The Netherlands
Poster #51 Post-exercise recovery period in patients with idiopathic ventricular arrhythmias
E. Parmon, T. Tulintseva, E. Berngardt, E. Panova, E. Shlaykto
Saint Petersburg, Russian Federation
Postural Orthostatic Tachycardia Syndrome
Poster #52 Regulation of circulation during exercise in adolescents with postural orthostatic tachycardia syndrome (POTS)
A. Goodloe, D. Soma, C.K. Brands, P.R. Fischer, P.T. Pianosi
Rochester, MN, USA
Poster #53 Neuropsychological profiles in adolescents with postural tachycardia syndrome (POTS)
K.D. Evankovich, L.K. Jarjour, A.M. Hernandez, I.T. Jarjour
Houston, TX, USA
Poster #54 How important is the T in POTS using pediatric versus adult diagnostic criteria for postural tachycardia?
I.T. Jarjour, A.M. Hernandez, L.K. Jarjour
Houston, TX, USA
Poster #55 Palpitations in postural tachycardia syndrome: what do they tell?
R.K. Khurana
Baltimore, MD, USA
Poster #56 The spectrum of neuropathic orthostatic tachycardia
W. Singer, T.L. Gehrking, P.A. Low
Rochester, MN, USA
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Poster #57 Origins of cognitive dysfunction in postural tachycardia syndrome
A.C. Arnold, K. Haman, E.M. Garland, S.Y. Paranjape, C.A. Shibao, I. Biaggioni, D. Robertson, S.R. Raj
Nashville, TN, USA
Poster #58 Pharmacological I(f) pacemaker current inhibition in a human postural tachycardia syndrome (POTS) model
C. Schroeder, K. Heusser, D. Rieck, F.C. Luft, J. Tank, J. Jordan
Hannover, Germany
Poster #59 Cardiovascular autonomic response to nitric oxide inhibition in POTS patients
I. Bonyhay, C. Gibbons, A. Benson, R. Freeman
Boston, MA, USA
Poster #60 Postural tachycardia syndrome: optimal duration of diagnostic orthostatic challenge
W.B. Plash, V. Nwazue, A. Diedrich, I. Biaggioni, E.M. Garland, S.Y. Paranjape, B.K. Black, W.D. Dupont, C.
Shibao, S.R. Raj
Nashville, TN, USA
Poster #61 Uncoupling of serum interleukin-6 and C-reactive protein in lean patients with postural tachycardia syndrome
L.E. Okamoto, S.R. Raj, A. Gamboa, C. Shibao, A.C. Arnold, A. Diedrich, G. Farley, D. Robertson, I. Biaggioni
Nashville, TN, USA
Orthostatic Hypotension & Syncope
Poster #62 Blood pressure effect of droxidopa in hypotensive individuals with spinal cord injury
J. Wecht, D. Rosado-Rivera, C. Yen, M. Radulovic, W. Bauman
Bronx, NY, USA
Poster #63 Prevalence of orthostatic hypotension in asymptomatic veterans
J. Wecht, C. Yen, S. Pena, A. Ivan, W. Bauman
Bronx, NY, USA
Poster #64 Combination ergotamine and caffeine for the treatment of orthostatic hypotension
C. Shibao, C.E. Ramirez, L.E. Okamoto, A.C. Arnold, A. Gamboa, P. Muppa, S.R. Raj, A. Diedrich, D. Robertson, I.
Biaggioni
Nashville, TN, USA
Poster #65 Abnormal autonomic findings in chronic subjective dizziness: sympathetic dysfunction or hyperactivity
H. Lee, H.A. Kim
Daegu, South Korea
Poster #66 Neurogenic mechanisms and venous physiology in patients with orthostatic intolerance
L. Saju, Z. Sun, R. Shields, F. Fouad-Tarazi
Cleveland, OH, USA
Poster #67 Mechanisms underlying the relationships between cardiovascular dysfunction and fall susceptibility in older adults
B.H. Shaw, S.N. Robinovitch, V.E. Claydon
Burnaby, BC, Canada
Poster #68 Arterial baroreflex asymmetry: an additional mechanism of orthostatic insufficiency in patients with non-cardiac
syncope
O.V. Mamontov, M.I. Bogachev, E.V. Shlyakhto
Saint-Petersburg, Russian Federation
Poster #69 Myoclonic jerks in syncope are probably generated in the cortex
J.G. van Dijk, R.D. Thijs, J. van Niekerk, W. Wieling, D.G. Benditt
Leiden, The Netherlands
Diabetic, Autoimmune & Other Autonomic Neuropathies
Poster #70 Glucoregulation and autonomic function in older male patients with diabetes mellitus and obstructive sleep apnea
J.L. Gilden, J. Cheng, B. Theckedath, P. Hung, J. Stoll
North Chicago, IL, USA
Poster #71 A case of paraneoplastic autonomic failure preceding Hodgkin’s lymphoma
P. Muppa, C.E. Ramirez, B. Black, D. Robertson, A. Peltier, S.R. Raj, C. Shibao, I. Biaggioni
Nashville, TN, USA
Poster #72 11-year follow-up of a case of autoimmune autonomic ganglionopathy
W. Singer, D.M. Sletten, T.L. Gehrking, A.K. Parsaik, P.A. Low
Rochester, MN, USA
Poster #73 Autonomic function test outcomes in diabetes mellitus
L.B. Tay, S. Srinivasan, C. Kang, T. Umapathi
Singapore
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10. 216 Clin Auton Res (2012) 22:207–258
Wednesday, October 31, 2012 (PAF), and Parkinson disease (PD). We hypothesized that cerebro-
spinal fluid levels of neuronal metabolites of catecholamines provide
neurochemical biomarkers of these disorders.
Oral Presentations Methods: We measured cerebrospinal fluid levels of catechols includ-
ing dopamine, norepinephrine, and their main respective neuronal
Alpha-synuclein as a cutaneous metabolites dihydroxyphenylacetic acid and dihydroxyphenylglycol in
biomarker of Parkinson disease MSA, PAF, and PD. Cerebrospinal fluid catechols were assayed in 146
subjects—54 MSA, 20 PAF, 34 PD, and 38 controls. In 14 patients
cerebrospinal fluid was obtained before or within 2 years after the onset
C.H. Gibbons, N. Wang, J. Lafo, R. Freeman of Parkinsonism.
Department of Neurology, Beth Israel Deaconess Medical Center, Results: The MSA, PAF, and PD groups all had lower cerebrospinal
Harvard Medical School, Boston, MA, USA fluid dihydroxyphenylacetic acid [1.32 ± (SEM) 0.12 nmol/l,
0.86 ± 0.09, 1.00 ± 0.09] than controls (2.15 ± 0.18 nmol/l;
Background: Parkinson’s disease is a multisystem neurodegenerative p 0.0001, p = 0.0002, p 0.0001). Dihydroxyphenylglycol was
disease characterized by the deposition of a-synuclein in the central, also lower in the three synucleinopathies (7.75 ± 0.42, 5.82 ± 0.65,
peripheral and enteric nervous system. Although the most prominent 8.82 ± 0.44 nmol/l) than controls (11.0 ± 0.62 nmol/l; p = 0.009,
manifestations of Parkinson’s disease are due to central, motor system p 0.0001, p 0.0001). Dihydroxyphenylacetic acid was lower and
neurodegeneration, there is widespread peripheral, autonomic and dihydroxyphenylglycol higher in PD than in PAF. Dihydroxyphen-
enteric nervous system degeneration with associated clinical features. ylacetic acid was 100 % sensitive at 89 % specificity in separating
Objective: To develop a biomarker for Parkinson disease. patients with recent onset of Parkinsonism from controls but was of
Methods: Fourteen patients with Parkinson disease and 10 age and no value in differentiating MSA from PD.
gender matched control subjects underwent skin biopsies at the distal Conclusions: Synucleinopathies feature cerebrospinal fluid neuro-
leg, distal thigh and proximal thigh. Skin biopsies were stained for chemical evidence for central dopamine and norepinephrine
PGP9.5, tyrosine hydroxylase, vasoactive intestinal peptide and deficiency. PD and PAF involve differential central dopaminergic
a-synuclein. The density of nerve fibers within specific dermal versus noradrenergic lesions. Cerebrospinal fluid dihydroxyphenyl-
organelles (pilomotor muscles and sweat glands) was calculated. acetic acid seems to provide a sensitive means to identify even
Because normal subjects have low levels of a-synuclein and Parkin- early PD. (Ref.: Goldstein et al., Brain 2012; Mar 26. [Epub ahead of
sonian subjects have autonomic nerve degeneration, we chose a print])
primary outcome as the proportion of these nerve fibers that contained
a-synuclein (determined by a-synuclein overlap with PGP 9.5),
defined as the a-synuclein ratio.
Results: Patients with PD had a distal sensory and autonomic neu-
ropathy expressed by loss of intra-epidermal, pilomotor and Prognostic indicators and clinical spectrum of MSA
sudomotor fibers (P 0.05 vs. controls). Patients with PD had higher based on autopsy-confirmed cases
a-synuclein ratios compared to controls within pilomotor nerves at the
distal leg (0.76 ± 0.19 vs. 0.26 ± 0.13, P 0.001), distal thigh
J.J. Figueroa, A.K. Parsaik, W. Singer, P. Sandroni, E.E. Benarroch,
(0.78 ± 0.16 vs. 0.28 ± 0.18; P 0.001) and proximal thigh
P.A. Low, J.H. Bower
(0.80 ± 0.13 vs. 0.32 ± 0.15; P 0.001). Patients with PD had
higher a-synuclein ratios compared to controls within sudomotor Department of Neurology, Mayo Clinic, Rochester, MN, USA
nerves at the distal leg (0.20 ± 0.11 vs. 0.02 ± 0.01, P 0.005),
distal thigh (0.18 ± 0.12 vs. 0.02 ± 0.01, P 0.005) and proximal Multiple system atrophy (MSA) is a progressive neurodegenerative
thigh (0.20 ± 0.14 vs. 0.02 ± 0.01, P 0.005). disorder characterized by motor dysfunction with autonomic failure.
Discussion: We have developed novel techniques to quantify the The goal of our study was to evaluate phenotype at presentation, rate of
density of autonomic nerve fiber innervation within specific dermal motor deterioration, and survival time after onset of motor and auto-
organelles, and have quantified the ratio of a-synuclein deposition nomic symptoms in a cohort of autopsy confirmed MSA patients. We
within these nerve fibers. We found significantly elevated a-synuclein retrospectively studied the Mayo Clinic cohort of 49 autopsy confirmed
deposition ratios within both sympathetic adrenergic pilomotor and MSA patients comprised of 33 (67 %) men and 16 (33 %) women.
sympathetic cholinergic sudomotor fibers in patients with Parkinson Disease duration from motor symptom onset (age 55.8 ± 7.1 years) to
disease. These findings suggest the a-synuclein ratio may be a bio- death (age 65.5 ± 8.6 years) was 9.7 ± 4.7 years. Clinical phenotype
marker in patients with Parkinson disease. at first evaluation was MSA-P in 29 (60 %), MSA-C in 16 (32 %),
Acknowledgement: Study supported by NIH NINDS K23NS050209 MSA-PC in 2 (4 %), and pure autonomic failure in 2 (4 %). At pre-
(CHG) and the RJG Foundation (CHG). sentation, patients had symmetric parkinsonism (27/32), retropulsion
(12/14), absent resting tremor (37/44), poor levodopa responsiveness
(18/22) and antecollis (5/7). Gait impairment was present at onset of
motor symptoms in 80 %. Time from onset of motor symptoms to first
CSF biomarkers of central and peripheral fall, wheelchair dependency and dysphagia was 1.5 ± 0.8, 4.4 ± 2.9
catecholamine deficiency in synucleinopathies and 6.1 ± 2.2 years respectively. Dysphagia requiring intervention
was associated with the shortest survival time (1.4 ± 1.2 years), fol-
lowed by wheelchair dependency (4.4 ± 2.9 years), fecal incontinence
D.S. Goldstein, L. Sewell, C. Holmes, C. Sims-O’Neil, Y. Sharabi (6.0 ± 3.8 years), presyncope and syncope (6.2 ± 4.3 years), need
Clinical Neurocardiology Section, NINDS/NIH, Bethesda, MD, USA for bladder catheterization (6.4 ± 4.1 years) and erectile dysfunction
(8.9 ± 5.0 years). This study reveals important clinical characteris-
Background: Central catecholamine deficiency characterizes primary tics and indicators of prognosis of MSA based on the natural history
chronic autonomic failure syndromes, including alpha-synucleinopa- of a large cohort of well-characterized autopsy-confirmed cases of
thies such as multiple system atrophy (MSA), pure autonomic failure MSA.
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11. Clin Auton Res (2012) 22:207–258 217
Mechanical stimulation of the feet improves gait loss of catecholaminergic neurons both in the striatum and the heart,
and increases cardiac vagal profile in Parkinson’s by assaying putamen and left ventricular apical concentrations of
catecholamines and the catecholamine precursor DOPA, the imme-
disease diate product of tyrosine hydroxylation, in post-mortem tissue from
patients with PD, pure autonomic failure (PAF, a rare Lewy body
F. Barbic1, M. Galli2, M. Canesi3, A. Porta4, V. Cimolin2, V. Bari4, disease that does not involve clinical evidence of central neurode-
L. Dalla Vecchia5, F. Dipaola1, V. Pacetti1, F. Meda1, I. Bianchi1, generation), or multiple system atrophy (MSA, a non-Lewy body
E. Brunetta1, R. Furlan1 form of alpha-synucleinopathy).
1
`
Unita Sincopi e Disturbi della Postura, Clinica Medica-IRCCS Methods: Putamen and apical myocardial tissue were obtained at
`
Istituto Clinico Humanitas, Rozzano (MI), Universita di Milano, autopsy within several hours of death in patients with end-stage PD,
Milano, Italy; 2Laboratorio per l’analisi della postura e del PAF, or MSA, and control patients (N = 4, 1, 1, and 6 as of this
movimento ‘‘L. Divieti’’, Politecnico di Milano, Milano, Italy; writing).
3
Centro Parkinson, CTO, Milano, Italy; 4Dipartimento di Tecnologie Results: PD patients had strikingly decreased myocardial norepi-
`
per la Salute, Istituto Ortopedico Galeazzi, Universita di Milano, nephrine and dopamine contents (by 93 and 94 %) compared to
Milano, Italy; 5IRCCS, Fondazione Maugeri, Milano, Italy controls (p = 0.008, p = 0.001). Decreased myocardial catechol-
amine contents were also evident in the PAF patient but were normal
Background: Alterations in sensorimotor central integration and/or in the MSA patient. Myocardial and putamen DOPA were decreased
peripheral sensory function might play a role in movement disorders in PD but to a lesser extent (about 2/3) than were the catecholamines.
in Parkinson’s disease (PD). Body mechanical stimulations was Post-mortem findings confirmed neuroimaging and neurochemical
recently found to improve gait in PD. In addition, alterations in car- data in the same patients during life.
diovascular autonomic control are common in PD, although their Conclusions: Lewy body diseases are associated with drastic myo-
relationships with movement disorders have not been fully addressed. cardial catecholamine depletion, demonstrating that PD is not only a
Aims: We tested the hypothesis that bilateral plantar stimulation can brain disease and movement disorder but is a more generalized dis-
improve gait and autonomic control of heart rate up to 24 h. ease that involves a form of dysautonomia. The decreases in
Methods: We studied 13 patients with idiopathic PD (mean age norepinephrine and dopamine in the putamen and myocardium seem
66 ± 2 years, BMI 23 ± 1 kg/m2, Hoehn–Yahr scale 2–4) on their greater than explained by denervation alone, consistent with
habitual pharmacological treatment. Every subject underwent decreased vesicular storage in residual nerves.
mechanical pressure (0.8 kg/mm2) at the big toe tip and at the big toe
metatarsal joint (plantar stimulation, PL) on both feet. Gait analysis
and spectral analysis of heart rate variability provided quantitative
indexes to assess movement disorders and cardiac autonomic profile
(HFRR, marker of cardiac vagal modulation) before and 24 h after Autonomic dysfunction in Parkinsonian LRRK2
plantar stimulation. mutation carriers
Results: Twenty-four hour after PL step mean length and gait velocity
increased (23.3 ± 6.2 from 537.7 ± 40.8 mm and 0.06 ± 0.02 from B. Tijero1, J.C. Gomez Esteban1, K. Berganzo1, V. Llorens2,
´
0.93 ± 0.09 m/s, respectively) and clock-wise rotation time H.J.J. Zarranz1
decreased (-1.8 ± 0.8 from 8.8 ± 1.2 s). In addition, HFRR 1
Movement Disorders and Autonomic Unit, Neurology Service,
increased (1.2E-04 ± 2.7E-04 from 4.5E-04 ± 1.9E-04 m/sec2) Cruces Hospital, Basque Health Service (Osakidetza), Department
compared to baseline, suggesting an enhancement of the cardiac vagal of Neurociences, University of the Basque Country, Spain; 2Nuclear
modulation. Medicine Service, Cruces Hospital, Baracaldo, Spain
Conclusions: 24 h after plantar stimulation, PD patients showed
changes in step length, gait velocity and body rotation time consistent
with an improvement of their movement disorder. Plantar stimulation Introduction: The aim of this study is to compare autonomic function
induced a concomitant increase in the vagal modulatory activity of in carriers of the LRRK2 (G2019S and R1441S) mutations and those
heart rate. with idiopathic Parkinson’s Disease (iPD) Patients.
Patients and methods: We studied 25 patients with a diagnosis of PD
according to the UK Parkinson’s Disease Society clinical diagnosis
criteria (6 had the G2019S and 6 R1441G, and 13 had iPD without
genetic mutations). All patients completed the SCOPA autonomic
Profound myocardial catecholamine depletion in Lewy questionnaire, underwent blood pressure and heart rate monitoring
during head up tilt with measurements of plasma norepinephrine,
body diseases
Valsalva maneuver and deep breathing, recording of sympathetic skin
response (SSR), and cardiac MIBG scintigraphy.
D.S. Goldstein, P. Sullivan, T. Jenkins, C. Holmes, M. Basile, Results: Scores of the SCOPA questionnaire were similar in patients
D.C. Mash, I.J. Kopin, Y. Sharabi with and without the LRRK2 mutations. Three of the iPD and one of
Clinical Neurocardiology Section, NINDS/NIH, Bethesda, MD, USA the LRRK2 carriers have orthostatic hypotension. During passive tilt,
iPD patients have minor Blood pressure increase than LRRK patients.
Background: Striatal dopamine depletion is a neurochemical hallmark Arterial pressure ‘‘overshoot’’ during phase IV of the Valsalva
of Parkinson disease (PD) and a major cause of the characteristic maneuver was less pronounced in patients with iPD than LRRK2
movement disorder. Accumulating evidence indicates that PD and mutation carriers. MIBG late (4 h) myocardial/mediastinal uptake
other Lewy body diseases also feature loss of cardiac sympathetic ratios are higher in LRRK2 mutation carriers than iPD patients
nerves, with decreased tyrosine hydroxylase, the rate-limiting enzyme (1.51 ± 0.28 vs. 1.32 ± 0.25, p = 0.05) Discussion: Carriers of the
in catecholamine biosynthesis, measured by semi-quantitative LRRK2 gene mutation had less autonomic impairment than those
immunohistochemistry. We applied a quantitative neurochemical with iPD as shown by higher cardiac MIBG uptake and less impair-
method to test whether Lewy body diseases characteristically involve ment of autonomic non-invasive test.
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12. 218 Clin Auton Res (2012) 22:207–258
Comparison of techniques for non-invasive assessment increase in blood pressure that we may be worried about. The point here is
of systemic hemodynamics in autonomic function that the delegated system—the Commander—can operate without
higher-order control to maintain our blood pressure, our heart rate, our
testing temperature essentially constant. Yet, the Master can exert higher-order
control that is either volitionally generated, such as during exercise or is
C. Sims-O’Neil, S. Pechnik, L. Sewell, L. Nez, D.S. Goldstein the product of cognitive or affective processes, such as worrying or the
Clinical Neurocardiology Section, NINDS/NIH, Bethesda, MD, USA experience of pain. In this talk, I will consider recent neuroimaging data
that highlight the different roles of cortical and subcortical structures in
Background: Neurogenic orthostatic hypotension is a cardinal mani- the generation of sympathetic outflow related to cardiovascular control.
festation of chronic autonomic failure (CAF). Systemic hemodynamic In particular, I will discuss the advantages of concurrent microneurog-
measurements include cardiac output (stroke volume times heart rate) raphy and functional magnetic resonance imaging (fMRI) in the
and total peripheral resistance (TPR, mean arterial pressure divided identification of functional roles for various bulbar and suprabulbar
by cardiac output). Normally, orthostasis decreases stroke volume, structures, with particular reference to medullary and hypothalamic
and heart rate and TPR increase reflexively. In CAF, TPR should fail nuclei, the insula, precuneus and prefrontal cortex.
to increase during orthostasis, because of baroreflex failure. This
study compared three non-invasive methods for measuring orthostatic
hemodynamic changes in CAF-impedance cardiography (BioZ), fin-
ger pulse contour (Nexfin), and gas rebreathing (Innocor).
Methods: A total of 78 subjects, 29 with and 49 without CAF, The middle cerebral artery dilates to sodium
underwent simultaneous hemodynamic measurements by BioZ, nitroprusside: a combined transcranial Doppler
Nexfin, or Innocor during supine rest and at 5 min of head-up tilt. and near infrared spectroscopy study
Results: Among supine subjects individual values by the three tech-
niques agreed for stroke volume and TPR. CAF patients had higher J.M Stewart1,2, C.E. Schwartz1, Z.R. Messer2, C.Terilli2,
TPR than did controls. During orthostasis, stroke volume decreased M.S. Medow1,2
by all three measurements. Clear differences emerged for calculated 1
Department of Physiology, New York Medical College, Valhalla,
orthostatic changes in TPR in CAF patients: BioZ reported a fall,
NY, USA; 2Department of Pediatrics, New York Medical College,
Nexfin no change, and Innocor an increase. In some patients, the
Valhalla, NY, USA
Innocor rebreathing maneuver itself decreased stroke volume as
indicated by the Nexfin device, especially during orthostasis.
Conclusions: All three non-invasive methods for tracking systemic Prior studies indicate that the middle cerebral artery (MCA) does not
hemodynamics yield similar results for TPR in supine subjects, and dilate in response to moderate orthostatic stress or changes in carbon
TPR during supine rest is increased in CAF. Impedance cardiography dioxide. Thus, measurements of cerebral blood flow velocity (CBFv) by
underestimates the orthostatic fall in stroke volume in CAF patients, transcranial Doppler ultrasound (TCD) are sufficient to estimate relative
resulting in a calculated orthostatic fall in TPR. Gas diffusion over- changes in cerebral blood flow under these conditions. Systemically
estimates the orthostatic fall in stroke volume, resulting in a administered nitric oxide (NO) donors decrease CBFv. However, NO
calculated orthostatic increase in TPR, due to artifactual effects of the dilates cerebral arteries of all sizes in primate models. We investigated
rebreathing maneuver required for the cardiac output measurement. whether systemic bolus injection of the NO donor sodium nitroprusside
Of the three methods, the finger pulse contour approach seems to (SNP) dilates the MCA and whether bolus phenylephrine constricts the
track most validly effects of orthostasis on TPR in CAF. MCA in 10 supine healthy volunteer subjects 18–24 years old. We
combined TCD of the MCA with near infrared spectroscopy (NIRS) over
the frontal cortex. Cerebral oxygenation and total hemoglobin increased
by 14 ± 1 and 15 ± 1 lM/L with 100 lg SNP despite hypotension, and
were reduced by 6 ± 1 and 7 ± 1 lM with 150 lg phenylephrine
Thursday, November 1, 2012 despite hypertension. SNP increased NIRS derived cerebral blood flow
estimates by approximately 40 % from baseline, while TCD derived
Oral Presentations CBFv decreased by 15 %. Phenylephrine decreased NIRS derived
cerebral blood flow estimates by approximately 11 % from baseline,
while TCD derived CBFv increased by 5 %. Studies using upright tilt and
Plenary Lecture lower body negative pressure were performed for comparison with the
literature and demonstrated similar relative changes in NIRS derived
Master and commander: the brain and the autonomic cerebral blood flow and TCD derived CBFv as orthostatic stress pro-
nervous system gressed. We conclude that the middle cerebral artery dilates to sodium
nitroprusside and constricts to phenylephrine but does not dilate during
orthostatic stress.
Vaughan G. Macefield, Ph.D.
School of Medicine, University of Western Sydney; Neuroscience
Research Australia, Sydney, Australia
Cerebral oxygenation, heart rate & blood pressure
The autonomic nervous system, so named because it operates automat- responses in congenital central hypoventilation
ically—without the need for conscious control—is very much a syndrome (CCHS) during exogenous ventilatory
‘‘delegated system’’: it faithfully follows a set of instructions to bring challenges: PHOX2B genotype/CCHS phenotype
about homeostasis, and attempts to maintain a stable internal environ-
ment in the presence of disease, yet these ‘‘presets’’ can be over-ridden by association
the requirements of higher-order control. We have all experienced the
racing heart rate, and the cold, clammy palms associated with anxiety. M.S. Carroll, P.P. Patwari, T.M. Stewart, C.D. Brogadir, A.S. Kenny,
Some of us may be in a state of chronic stress and are experiencing an C.M. Rand, D.E. Weese-Mayer
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13. Clin Auton Res (2012) 22:207–258 219
Center for Autonomic Medicine in Pediatrics, Ann and Robert H. mean. Diffuse denervation was defined by both septal and free wall
Lurie Children’s Hospital, Northwestern University Feinberg School radioactivity more than 2 standard deviations below the normal mean.
of Medicine, Chicago, IL, USA Results: The time between localized and diffuse denervation averaged
2.5 ± (SEM) 0.8 years. The mean change in septal radioactivity
Congenital central hypoventilation syndrome (CCHS) is a disorder of during this interval was -56 ± 10 %, corresponding to 22 % loss per
respiratory and autonomic regulation, characterized by hypoventila- year. In one patient followed over more than 12 years, cardiac sym-
tion and diminished/absent ventilatory responses to hypoxia/ pathetic innervation was normal for 6 years, with subsequent rapid
hypercarbia. However, ventilatory responses in CCHS have not been loss of free wall radioactivity and then equally rapid loss of septal
evaluated subsequent to identification of PHOX2B as the disease- radioactivity with a delay of about 2 years.
defining gene, and recognition that the longer polyalanine repeat Conclusions: In Parkinson disease, once there is evidence for loss of
expansion mutations (PARMs) are typically associated with more sympathetic nerves in the left ventricular free wall, septal denervation
severe clinical features. We therefore hypothesized that cerebral rapidly ensues, resulting in remarkably swift diffuse denervation by
oxygenation and cardiovascular metrics in response to exogenous 2–3 years later. Follow-up cardiac sympathetic neuroimaging in
ventilatory challenges (EVC) would show a graded deficit correlated patients with localized cardiac denervation therefore may be a basis
with PHOX2B genotype among CCHS patients with PARMs. Thirty- for a novel, quantitative means to assess potential treatments to retard
one children and young adults (5 months–27 years; 14 female) with the loss of catecholaminergic neurons that characterizes Parkinson
CCHS were tested during wakefulness with 45 separate clinical EVCs disease.
(each with 4 distinct gas mixtures) during continuous comprehensive
physiological monitoring. Three-minute challenges were adminis-
tered between 3 min room-air periods, with minimal ventilatory
support: Hyperoxia (100 % O2), hyperoxia-hypercarbia (95 % O2/
Parental attribution of symptoms in adolescents
5 % CO2) and hypoxia-hypercarbia (14 % O2/7 % CO2). The fourth
challenge, hypoxia, consisted of 5 or 7 tidal breaths of N2. A com- with postural tachycardia syndrome and its relation
parison group of 4 young men (18–21 years) were monitored while to child functioning and psychological variables
receiving all but the hypoxia challenge. Percent change from baseline
(±SEM) was calculated during each challenge for the cerebral near E.M. Keating1, R.M. Antiel2, K.E. Weiss3, D. Wallace4,
infrared spectroscopy (cNIRS) channel, mean blood pressure, and P.R. Fischer5, C. Harbeck-Weber3
heart rate. Significance was assessed at p 0.05 (paired t test). The 3 1
Mayo Medical School, Mayo Clinic, Rochester, MN, USA;
most common PARM genotypes were compared to assess genotype- 2
Department of General Surgery, Mayo Clinic, Rochester, MN, USA;
phenotype association. Though the cNIRS response was not consis- 3
Department of Psychiatry and Psychology, Mayo Clinic, Rochester,
tently associated with polyalanine repeat length, it was impaired/ MN, USA; 4Integrative Pain Management, Children’s Mercy
attenuated in CCHS versus controls during the hypoxia-hypercarbia Hospital, Kansas City, MO, USA; 5Department of Pediatric
challenge. Blood pressure responses were variable, but showed a and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
CO2-dependent increase in CCHS. Heart rate was suppressed by
hyperoxia in CCHS, but increased in the combined hypoxia-hyper-
carbia challenge. The heart rate response to the hypoxia-hypercarbia Background: Chronic pain is a common symptom in adolescents with
challenge was consistently correlated with polyalanine repeat length postural orthostatic tachycardia syndrome (POTS), and it is frequently
(blunted response with increasing PARM length). Overall, compre- associated with impairment in functioning. The manner in which
hensive physiological evaluation during ventilatory challenges parents respond to children’s pain may predict children’s functional
indicated residual responsiveness in CCHS, providing a potential disability, and parental responses to the pain are related to parental
fulcrum for therapeutic interventions. beliefs about the causes of the pain. The Parent Attribution Ques-
tionnaire (PAQ) was developed to assess these parental attributions
regarding their child’s pain. We evaluated parent attributions of
symptoms in adolescents with POTS in order to determine how they
Time course of cardiac sympathetic denervation are related to their child’s functioning.
in Parkinson disease Methods: 141 adolescent patients with chronic pain and clinical
symptoms suggestive of POTS were seen in a multidisciplinary
chronic pain clinic at Mayo Clinic. Of these patients, 37 were iden-
D.S. Goldstein tified as having POTS with a postural heart range change of at least 40
Clinical Neurocardiology Section, NINDS/NIH, Bethesda, MD, USA beats per minute on tilt table testing. Parents of 114 of these patients
completed a demographic questionnaire and PAQ. The PAQ is a
Background: Parkinson disease entails not only nigrostriatal dopa- 19-item questionnaire that asks parents to indicate the extent they
minergic but also cardiac noradrenergic denervation, which can occur believe medical (9 items) and psychosocial factors (10 items) account
before clinical onset of the movement disorder. The neuropathologic for their child’s health condition.
process in the heart appears to proceed retrogradely and centripetally. Results: In patients with chronic pain who have symptoms suggestive
Localized denervation in the left ventricular myocardial free wall of possible autonomic dysfunction, higher parental attribution of
progresses to diffuse denervation, with late loss of interventricular symptoms to medical causes was associated with increased levels
septal innervation. We analyzed neuroimaging data from patients with of functional disability (r = 0.33, p 0.001). Parental attribution of
localized denervation to estimate the loss rate of cardiac catechol- symptoms to psychological causes was linked to depression only in
aminergic neurons in Parkinson disease. patients without POTS (r = 0.53, p 0.01) but not in those with
Methods: Serial 18F-dopamine positron emission tomographic scan- POTS.
ning data in Parkinson disease patients were reviewed and 4 patients Conclusions: Functional disability in adolescents with POTS relates
identified who had localized followed by diffuse denervation. to the degree to which parents attribute the child’s symptoms to a
Localized denervation was defined by free wall 18F-dopamine-derived medical problem. It is likely that helping parents avoid over-accep-
radioactivity more than 2 standard deviations below the normal mean tance of incurable medical problems as causing pain could help
and septal radioactivity within 2 standard deviations of the normal children attain better functioning.
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14. 220 Clin Auton Res (2012) 22:207–258
Cardiovagal sensitivity and orthostatic heart rate Background: Parental responses to pain may have an important
response in young patients with orthostatic intolerance impact on adolescent pain outcomes. Approximately 10 % of
adolescents suffer from autonomic dysfunction marked by ortho-
static intolerance, severe fatigue, and chronic pain. We sought to
W. Singer, A.K. Parsaik, E.E. Benarroch, P. Sandroni, P.A. Low examine if parental responses to these symptoms are related to
Department of Neurology, Mayo Clinic, Rochester, MN, USA their child’s functioning, psychological well-being, and pain
acceptance.
Background and Objective: Orthostatic intolerance (OI) is increas- Methods: Participants included 141 adolescents with chronic pain
ingly recognized among adolescents but pathophysiologic and symptoms of orthostatic intolerance who were seen in a mul-
mechanisms underlying this condition remain poorly understood. tidisciplinary pain clinic at the Mayo Clinic. Of the 141 patients, 37
These patients typically have normal autonomic function as assessed (26 %) had excessive postural tachycardia (PT) with a heart rate
using standardized autonomic testing. We frequently see high or very change of at least 40 bpm on tilt table testing. Participants com-
high values for cardiovagal indices in these patients and made the pleted the Functional Disability Inventory, the Center of
observation that those with unusually high HR responses to deep Epidemiological Studies—Depression Scale, the Spence Children’s
breathing (HRDB) and Valsalva maneuver (VM, Valsalva Anxiety Scale, and the Chronic Pain Acceptance Questionnaire,
ratio = VR) also seem to have the most excessive HR responses to adolescent version. Parents of 103 of these patients completed the
tilt. Such relationship—if present—would be intriguing in terms of Parent Response to Pain Questionnaire—Revised, which measures 4
mechanisms underlying the magnitude of HR responses to tilt and of theoretically driven parental factors: solicitous behaviors, secondary
OI; factors such as excessive cardiac vagal modulation and baroreflex gain, promoting adaptive behavior, and encouragement of specific
sensitivity might be implicated. We therefore sought to evaluate pain management.
whether the magnitude of cardiovagal indices predicts the orthostatic Results: Parent solicitous behaviors were significantly related to
rise in HR and whether the pattern of findings reveals insights into the anxiety (r = 0.21, p 0.05). Parent report of secondary gain was
pathophysiology underlying adolescent OI. correlated with depression (r = 0.57, p 0.01) and negatively related
Methods: 100 adolescent patients were randomly selected from a to acceptance (r = -0.40, p 0.05). Upon further examination of the
large cohort of patients referred to our laboratory for evaluation of sub-sample of patients with excessive PT, parent report of secondary
symptoms of OI. HRDB and VR were quantified using standard gain was related to functional disability (r = 0.39, p 0.05) and
techniques. Vagal baroreflex sensitivity (vBRS) was defined as slope parent encouragement to use specific pain management skills was
between systolic blood pressure (BP) decline during phase II and inversely associated with depression (r = -0.069, p 0.05).
resulting change in RR interval. HR and BP responses to tilt were Conclusions: Differential parental responses to pain are significantly
assessed using 30 s data averages, BP responses to the VM were related to adolescent anxiety, depression, and pain acceptance. Fur-
assessed using systolic BP at the different phases of the maneuver. thermore, in patients with co-morbid orthostatic intolerance parental
Correlations between different parameters were tested using Pear- responses are associated with functional disability and depression.
son’s r. These findings suggest that parental responses to adolescent pain are
Results: HRDB and vBRS were not correlated with DHR or DBP related to patient outcomes and could have implications for effective
during tilt. However, VR was significantly correlated with DHR interventions.
(p = 0.001). While VR was also strongly correlated with the BP
changes during early phase II and phase IV of the VM, as well as the
sum of both, only one of these BP indices (phase IV) was weakly
correlated with DHR during tilt. No correlations were seen between Relationship between ganglionic long-term potentiation
BP and HR responses to tilt.
(LTP) and homeostatic synaptic plasticity
Conclusions: These findings argue against excessive cardiac vagal
modulation or excessive BRS underlying the excessive orthostatic rise in experimental autoimmune autonomic
in HR in adolescents with OI. The pattern of findings would rather ganglionopathy (EAAG)
suggest that the mechanism underlying the excessive orthostatic rise
in HR also results in excessive BP responses to the VM and conse- Z. Wang, S. Vernino
quently excessive VR. This putative mechanism remains subject to UT Southwestern University, Dallas, TX, USA
further study. Supported by NIH (K23NS075141, U54NS065736,
UL1RR24150) and Mayo Funds.
The autonomic nervous system must be able to adapt to maintain
homeostasis. Plasticity of ganglionic synaptic transmission repre-
sents one important mechanism of autonomic adaptation. We have
shown that homeostatic plasticity of ganglionic neurotransmission
Parental response to pain: the impact on functional occurs in EAAG. In EAAG, there is a reduction in synaptic gan-
disability, depression, anxiety, and pain acceptance glionic AChRs followed by a compensatory increase in
neurotransmitter release to help offset the deficit in synaptic trans-
in adolescents with chronic pain and orthostatic mission. Homeostatic plasticity is quite different from classical use-
intolerance dependent LTP. Both types of plasticity occur in autonomic ganglia,
so the ganglionic synapse is an ideal system in which to study the
R.M. Antiel1, E.M. Keating2, K.E. Weiss3, D.P. Wallace4, interrelationship between these two forms of synaptic plasticity. We
P.R. Fischer5, C. Harbeck-Weber3 studied synaptic transmission in isolated mouse superior cervical
1
Department of General Surgery, Mayo Clinic, Rochester, MN, USA; ganglia using microelectrode and patch clamp electrophysiology
2
Mayo Medical School, Rochester, MN, USA; methods. High frequency stimulation (HFS) of the preganglionic
3
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, nerve (20 Hz for 20 s) in control ganglia induces a long-lasting
MN, USA; 4Integrative Pain Management, Children’s Mercy increase in synaptic transmission due to increased probability of
Hospital, Kansas City, MO, USA; 5Department of Pediatric synaptic release. A second HFS does not produce further enhance-
and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA ment. Ganglia from mice with EAAG fail to show LTP. Inhibitors
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15. Clin Auton Res (2012) 22:207–258 221
of nitric oxide synthase prevent the induction of LTP in control baroreflex failure causes volume intolerance remains unknown. The
ganglia and also cause a normalization of presynaptic release in aim of this investigation is to examine the mechanism of baroreflex
EAAG ganglia. These findings indicate that homeostatic plasticity of failure induced volume intolerance.
synaptic transmission (as occurs in the EAAG model) shares com- Method: In 6 anesthetized dogs, we isolated carotid sinuses and
mon molecular mechanism with use-dependent plasticity (ganglionic controlled intra-carotid sinus pressure (CSP), while measuring the left
LTP). The implication is that pharmacological manipulation of (PLA) and right (PRA) atrial pressure, arterial pressure (AP) and
ganglionic LTP may be a useful therapeutic option for patients with aortic flow (CO). We closed the baroreflex feedback loop by matching
autonomic disorders. CSP to instantaneous AP, whereas opened by maintaining CSP con-
stant independent of AP. We infused total of 22.5 ml/kg of dextran in
an increment of 2.5 ml/kg. In each step, we measured PLA, PRA and
CO in both open and closed loop conditions. We fitted the CO curve
Methionine sulfoxide reductase A: a novel molecular to a logarithmic function and determined its functional slope S, as a
determinant of baroreflex sensitivity, blood pressure measure of cardiac performance, for the left (SL) and right (SR)
and hypertensive end-organ damage ventricle. We determined stressed blood volume and mean circulatory
filling pressure (Pmcf).
Results: Increases in PLA was lower in the closed loop than in the
R. Sabharwal, R. El Accaoui, M.K. Davis, J.A. Goeken, R. Weiss,
open loop condition (9 ± 3 vs. 12 ± 5 mmHg, p 0.05). Both SL
F.M. Abboud, D. Meyerholz, M.W. Chapleau
and SR were lower in the closed loop than in the open loop condition
The University of Iowa and Veterans Affairs Medical Center, (SL: 23 ± 5 vs. 27 ± 6 ml/kg/min, p 0.01, SR: 23 ± 5 vs.
Iowa City, IA, USA 27 ± 6 ml/kg/min, p 0.01) indicating that the baroreflex lowers
cardiac performance against volume overload. Pmcf after infusion of
Methionine sulfoxide reductase-A (MsrA) selectively reverses oxi- 22.5 ml/kg of dextran was lower in the closed loop than in the open
dation of methionine residues in proteins, thereby protecting against loop condition (10.8 ± 0.5 vs. 12.8 ± 1.1 mmHg, p 0.005).
oxidative stress-induced cellular damage and dysfunction. We Conclusion: In response to volume challenge, the baroreflex lowered
hypothesized that MsrA is required for normal autonomic and blood cardiac performance and prevented the increases in Pmcf. Although
pressure (BP) regulation, and protects against hypertension-induced those two responses have antagonizing impact on PLA, the fact that
end-organ damage. BP, heart rate (HR) and locomotor activity were the baroreflex lowered PLA indicates that the baroreflex induced
measured in MsrA deficient (n = 13) and control C57BL/6 (n = 7) changes in stressed volume is the central mechanism preventing
mice by telemetry, before and during infusion of angiotensin II (Ang pulmonary edema.
II) (1,000 ng/kg/min for 4 weeks). Under basal conditions, MsrA-/-
mice exhibited mild hypertension (117 ± 3 vs. 107 ± 2 mmHg) and
decreased locomotor activity. During periods when activity levels
were similar, the hypertension in MsrA-/- mice was exacerbated Prostaglandin D synthase is critical for development
(135 ± 2 vs. 103 ± 2 mmHg). MsrA-/- mice also exhibited of chronic angiotensin II-salt hypertension in the rat
decreases in spontaneous baroreflex sensitivity (BRS, sequence
technique) (0.9 ± 0.1 vs. 2.2 ± 0.1 ms/mmHg) and cardiovagal tone G.D. Fink, N. Asirvatham-Jeyaraj
(HR response to cholinergic receptor blocker methylatro-
Department of Pharmacology and Toxicology, Michigan State
pine = +32 ± 5 vs. +100 ± 17 bpm); and increases in BP variability
University, East Lansing, MI, USA
(BPV) and sympathetic tone (HR response to beta adrenergic receptor
blocker propranolol) (P 0.05). Ang II increased mean BP, BPV and
sympathetic tone; and decreased BRS and vagal tone, with MsrA-/- Chronic infusion of angiotensin II (150 ng/kg/min, sc) into rats
mice exhibiting markedly enhanced responses (P 0.05). Adminis- ingesting a high salt diet (4.0 % NaCl) produces sustained hyper-
tration of the antioxidant tempol (1 mM, drinking water) reversed the tension (AngII-salt HT) caused in part by increased splanchnic
Ang II-induced hypertension and autonomic dysregulation. Ang II- sympathetic nerve activity. Previous work suggests that cyclooxy-
infused MsrA-/- mice (n = 10) exhibited left ventricular dysfunc- genase products generated in the brain during the first few days of
tion, increased diameter of the ascending aorta (echocardiography), exposure to angiotensin II are necessary for these effects. Analyses of
and abdominal aortic aneurysms. We conclude that MsrA: (1) is eicosanoid pathway gene expression in the brain during the early
required for normal BP, BRS and sympathovagal balance under basal phase of AngII-salt HT highlighted lipocalin-type prostaglandin D
conditions; (2) protects against Ang II-induced hypertension, auto- synthase (L-PGDS) as a possible critical element in the response. To
nomic dysfunction and end-organ damage; and (3) is a novel test that idea we continuously administered the highly selective
therapeutic target in hypertension. (HL14388, VA) L-PGDS inhibitor AT-56 into the brain of rats via intracerebroven-
tricular (icv) infusion (6.6 lmol/h). We then induced our standard
14-day model of AngII-salt HT starting 5 days after icv AT-56
administration had begun. Rats receiving only icv vehicle served as
Baroreflex induced changes in stressed blood volume, controls. Blood pressure was measured continuously throughout the
not cardiac output curve, is the central mechanism experiment by radiotelemetry. Sympathetic control of blood pressure
was estimated from the depressor response to acute ganglion blockade
preventing volume load induced pulmonary edema
with hexamethonium (30 mg/kg, ip). Control rats showed typical
elevations in blood pressure during AngII infusion and a significantly
T. Sakamoto, T. Kakino, K. Sunagawa enhanced depressor response to ganglion blockade on day 8 after
Department of Cardiovascular Medicine, Kyushu University, starting AngII. Rats receiving icv AT-56 exhibited no change in basal
Fukuoka, Japan blood pressure but had a markedly and significantly reduced blood
pressure and sympathetic response to AngII infusion compared to
Background: We previously demonstrated that baroreflex failure control rats. Systemic administration of AT-56 via continuous sub-
predisposes volume induced pulmonary edema. Since the baroreflex cutaneous infusion (6.6 lmol/h) also completely prevented the
changes both cardiac and vascular properties, how exactly the increases in blood pressure and sympathetic pressor activity normally
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16. 222 Clin Auton Res (2012) 22:207–258
observed during AngII infusion. These studies reveal that L-PGDS, well as cardiac arrhythmia is relatively uncommon compared to larger
likely in the brain, is a necessary component of AngII-salt HT and animals or humans, since high quality continuous long term ECG and
sympathoexcitation. Since systemic inflammation, sleep deprivation arterial blood pressure (APB) recordings as well as the techniques for
and obesity are all associated with increased brain levels of prosta- analysis of heart rate (HR), heart rate variability (HRV) and
glandin D and sympathoexcitation, our results may have broad arrhythmia detection in the mouse present technical and computa-
implications for understanding neurogenic forms of hypertension. tional challenges.
Methods: We present data from several studies involving murine ECG
and ABP signals from implanted wireless radiofrequency transmitters.
We describe and compare different methods of digital signal pro-
The central chemoreflex activation induces cessing, heart beat and arrhythmia detection and classification,
sympathoexcitation and resets the arterial baroreflex computation of baroreflex sensitivity, time domain and frequency
without compromising its pressure stabilizing function domain HRV parameters, construction of composite plots for
dynamics of HR and HRV data over time during interventional
studies from an aspect specific to the mouse model. We illustrate
K. Saku, K. Sunagawa
technical challenges, common mistakes and solutions throughout the
Department of Cardiovascular Medicine, Kyushu University, process from telemetry to the analysis results presentation.
Fukuoka, Japan Results: During a decade of experience with murine ECG signal
analysis, we have developed a toolbox of techniques specifically
Background: The augmented chemoreflex and impaired baroreflex in tailored to the mouse model. Here we demonstrate the technical
heart failure result in excessive sympathoexcitation and poor prog- requirements for signal quality and processing, how wavelet based
nosis. However, how the chemoreflex interacts with the baroreflex visualizations and spectrograms can significantly aid in the charac-
remains unknown. The purpose of this investigation was to examine terization of dynamic changes and the detection of anomalies and
the impact of chemoreflex on the baroreflex function under the open- artifacts and how specific plotting techniques can reveal unexpected
loop condition. findings such as multiple transient atrial pacemakers during carbachol
Methods and Results: In 7 vagotomized rats, we vascularily isolated challenge experiments. We show the use of machine learning algo-
the bilateral carotid sinuses, controlled carotid sinus pressure (CSP) rithms for the automatic detection and reliable subclassification of
and measured SNA at the celiac ganglia and arterial pressure (AP). ventricular tachycardia and premature contractions after myocardial
We activated the central chemoreflex by hypercapnia (inhalation of infarction with pattern recognition techniques such as artificial neural
3 % CO2). Under the open baroreflex loop, we compared the changes networks in large data sets from long term ECG signals. Finally, we
in AP and SNA in response to CSP with/without hypercapnia. show that parallel processing and general-purpose computing on
Increasing CSP stepwise from 60 to 170 mmHg sigmoidally sup- graphics processing units allow for accelerated analysis of continuous
pressed SNA, whereas the SNA suppression linearly decreased AP. mouse ECG recordings over days with millions of heart beats as well
Hypercapnia markedly increased SNA (DSNA = 53.4 ± 7.1 %, as for providing near real-time computation of advanced analysis
p 0.01) irrespective of CSP indicating the resetting of the CSP– output during experiments.
SNA relationship (the neural arc). Hypercapnia increased the setpoint
pressure (168.6 ± 8.2 vs. 188.3 ± 8.1 mmHg, p 0.01) of neural
arc, whereas did not alter the SNA–AP relationship (peripheral arc).
The total loop gain from CSP to AP at the operating point remained Streeten Lecture
unchanged (-1.09 ± 0.13 vs. -1.43 ± 0.18, p = ns). Random per-
turbation of CSP with binary white noise sequences indicated that The ‘‘ups and downs’’ of blood pressure & baroreflex
hypercapnia did not affect the transfer functions of the neural or
sensitivity—a historical and personal perspective
peripheral arcs. Therefore, the chemoreflex activation did not impact on
the baroreflex dynamic characteristics of pressure stabilizing function.
Conclusion: Hypercapnia resets the baroreflex neural arc upward and Mark W. Chapleau, Ph.D.
increases arterial pressure, while does not affect baroreflex pressure University of Iowa and Veterans Affairs Medical Center, Iowa City,
stabilizing characteristics. We conclude that the central chemoreflex IA, USA
modifies hemodynamics via sympathoexcitation without compro-
mising baroreflex function. The augmented chemoreflex in heart The baroreceptor reflex is a powerful regulator of blood pressure
failure cannot be responsible for the baroreflex dysfunction. How (BP). Increases and decreases in BP are buffered by baroreflex-
chemoreflex induced changes in hemodynamics contribute to CO2 mediated autonomic and circulatory adjustments. By minimizing BP
homeostasis remains to be seen. variability, the baroreflex protects against ischemia, syncope and end-
organ damage (e.g., vascular and cardiac hypertrophy, renal failure,
stroke). The baroreflex also favorably influences cardiac sympath-
ovagal balance, and consequently affects the electrical properties of
Advanced techniques and pitfalls of autonomic function the heart. Decreased baroreflex sensitivity (BRS) for control of heart
assessment and arrhythmia analysis in the mouse model rate (HR) predicts future arrhythmias and decreased survival in
patients with myocardial infarction, heart failure and diabetes;
increased BRS is protective. In my presentation, I will review
C.M. Welzig1, J.B. Galper2 experimental approaches and key discoveries related to the physiol-
1
Department of Neurosciences, Medical University of South Carolina, ogy and pathophysiology of the baroreceptor reflex, with emphasis on
Charleston, SC, USA; 2Molecular Cardiology Research Institute, studies leading up to and including work in my laboratory. Results
Tufts Medical Center, Boston, MA, USA obtained using a variety of approaches will be presented including
recordings of baroreceptor afferent and sympathetic efferent nerve
Background: Mice are very frequently employed as a mammalian activity; telemetry-based measurements of cardiovascular and derived
research model and are used in a wide spectrum of experimental autonomic indices in conscious, genetically modified mice; electro-
protocols. However, the study of autonomic function and disorders as physiological and imaging studies of isolated baroreceptor neurons in
123