Mechanisms of Vasovagal Syncope
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 14 - 29 |
| Updated: | 1/16/2019 |
| Start Date: | February 2013 |
| End Date: | July 2019 |
Vasovagal Syncope (simple postural faint) is the most common cause of acute loss of
consciousness. Postural tachycardia syndrome(POTS) is the most common chronic form of
postural lightheadedness. Together they afflict many Americans, mostly young women, who are
prevented from gainful employ or school attendance. The underlying mechanism is not known.
Our past work suggests that a simple molecule, nitric oxide, acts to subvert normal blood
flow controls causing blood to pool in the gut when standing. Our proposal will show the
mechanism behind this problem and will indicate effective medical treatments. Patients will
be compared to healthy control subjects.
consciousness. Postural tachycardia syndrome(POTS) is the most common chronic form of
postural lightheadedness. Together they afflict many Americans, mostly young women, who are
prevented from gainful employ or school attendance. The underlying mechanism is not known.
Our past work suggests that a simple molecule, nitric oxide, acts to subvert normal blood
flow controls causing blood to pool in the gut when standing. Our proposal will show the
mechanism behind this problem and will indicate effective medical treatments. Patients will
be compared to healthy control subjects.
Vasovagal Syncope (VVS,simple faint) is the most common cause of transient loss of
consciousness and is the acute episodic form of orthostatic intolerance(OI). Postural
tachycardia syndrome (POTS) is the common chronic form of OI. Both are defined by
debilitating symptoms and signs while upright relieved by recumbency. Pathophysiological
mechanisms have remained elusive although our past work shows that excessive upright central
hypovolemia results from splanchnic pooling due to defective splanchnic arterial and venous
constriction. Preliminary data support the hypothesis that production of nitric oxide (NO) is
enhanced in these patients resulting in reduced sympathetic noradrenergic neurotransmission
at pre-junctional and post-junctional sites. Our approach is two-fold: 1) We will use
intradermal microdialysis and laser Doppler flowmetry (LDF) to delineate the microvascular
mechanisms of NO modulation of noradrenergic neurotransmission free of confounding systemic
reflex changes. 2) We will systemically apply this mechanism to a model of orthostatic
stress, lower body negative pressure(LBNP), while measuring cardiac output by inert gas
rebreathing, regional blood volume, and regional blood flow using plethysmographic techniques
focusing on splanchnic changes, and muscle sympathetic nerve activity by peroneal
microneurography. We will study synaptic peripheral neurotransmission of Norepinephrine and
how it is affected by supplemental NO and by nitric oxide synthase inhibitor.
consciousness and is the acute episodic form of orthostatic intolerance(OI). Postural
tachycardia syndrome (POTS) is the common chronic form of OI. Both are defined by
debilitating symptoms and signs while upright relieved by recumbency. Pathophysiological
mechanisms have remained elusive although our past work shows that excessive upright central
hypovolemia results from splanchnic pooling due to defective splanchnic arterial and venous
constriction. Preliminary data support the hypothesis that production of nitric oxide (NO) is
enhanced in these patients resulting in reduced sympathetic noradrenergic neurotransmission
at pre-junctional and post-junctional sites. Our approach is two-fold: 1) We will use
intradermal microdialysis and laser Doppler flowmetry (LDF) to delineate the microvascular
mechanisms of NO modulation of noradrenergic neurotransmission free of confounding systemic
reflex changes. 2) We will systemically apply this mechanism to a model of orthostatic
stress, lower body negative pressure(LBNP), while measuring cardiac output by inert gas
rebreathing, regional blood volume, and regional blood flow using plethysmographic techniques
focusing on splanchnic changes, and muscle sympathetic nerve activity by peroneal
microneurography. We will study synaptic peripheral neurotransmission of Norepinephrine and
how it is affected by supplemental NO and by nitric oxide synthase inhibitor.
Inclusion Criteria:
1. POTS patients referred for day to day orthostatic intolerance with greater than 3
symptoms for greater than 3 months and will have the diagnosis of symptomatic postural
tachycardia made during a screening tilt table test :
- dizziness
- nausea and vomiting
- palpitations
- fatigue
- headache
- exercise intolerance
- blurred vision
- abnormal sweating heat.
2. Vasovagal Syncope patients will have at least 3 episodes of fainting episodes in the
past year.
3. Healthy control subjects
Cases will be between the ages of 14 and 29 years old Cases will have normal physical
examination, and normal electrocardiographic and echocardiographic evaluations.
Only those free from heart disease, and from systemic illness will be eligible to
participate.
This excludes patients with illnesses and disease states known to be associated with
endothelial cell dysfunction such as diabetes, renal disease, congestive heart failure,
systemic hypertension, acute and chronic inflammatory diseases, neoplasm, immune mediated
disease, trauma, morbid obesity and peripheral vascular disease.
At the time of testing all patients and control subjects must refrain from vasoactive drugs
for two weeks. Please check with us about any medication that you are taking.
Exclusion Criteria:
- Cardiovascular causes of syncope
- An active medical condition that may explain the diagnosis
- A previous medical condition with undocumented resolution that may explain the
diagnosis
- Past or present major psychiatric disorder
- Substance abuse within 2 years before onset of symptoms.
We found this trial at
1
site
Hawthorne, New York 10532
Principal Investigator: Julian M. Stewart, M.D., Ph.D.
Phone: 914-593-8888
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