Mechanisms of Vasovagal Syncope

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Questionnaires

 

Consent

 

 

What comprises the study population? 

    We will recruit young adults aged 14-29 years of both genders who have had 3 or more episodes of vasovagal syncope or imminent syncope (presyncope) within the past year.  We will also recruit patients in our on-going study of POTS determined to have splanchnic neuropathic POTS ("normal flow POTS").and age/sex and body mass matched healthy volunteers. 

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What is the hypothesis and importance

Vasovagal syncope (VVS, 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.  Our past work suggests that a simple molecule, nitric oxide (NO), acts to subvert normal blood flow controls causing blood to pool in the gut circulation (splanchnic circulation) when upright. Our proposal will show the mechanism behind this problem and will indicate effective medical treatments. 

To date there is no cure for simple faint because its mechanism is incompletely understood. The proposed experiments look at the way NO might alter the ways the sympathetic nervous system works. The proposed approaches combine testing molecular hypothesis in the skin (cutaneous circulation) using minimally invasive laser-Doppler and microdialysis techniques. This will determine how small vessels (microvessels) work in these forms of orthostatic intolerance (OI). Microvascular data are then combined to predict systemic, whole body  responses using novel measures of blood flow and microneurography which measures how sympathetic nerves work. Microvascular and macrovascular approaches are united to understand pathophysiology.  

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    What are the symptoms and findings in patients

    We are recruiting patients with frequent fainting that is not due to heart disease or due to conditions that cause nerve damage. We are also recruiting certain patients with postural tachycardia . These are expected to be found among patients that we encounter for research-related investigation of POTS. 

    The key feature of postural VVS is loss of consciousness while upright, that is of rapid onset, brief, and spontaneously terminating. In all cases, loss of consciousness and postural tone occurs (i.e. the patient falls down) and this is ultimately due to a critical reduction in brain blood flow. Most patients have low blood pressure as the cause of reduced brain blood flow. While syncope may occur due to heart disease at all ages the most common variant is postural VVS in the young. 

    The key features of POTS is symptoms which are most prominent when standing. However, in some, findings are present supine (lying down)  but worsened standing. Symptoms of POTS include dizziness in all patients, exercise provoked symptoms and thus exercise intolerance, excessive fatigue, nausea and abdominal pain, headache, shortness of breath and deep breathing, weakness, shakiness and postural anxiety, pallor, and neurocognitive loss (difficulty thinking). These occur on a day-to-day basis. The symptoms overlap with the case definition of chronic fatigue syndrome (CFS) and POTS is often found in CFS in the young. Fainting is relatively uncommon during daily life. 

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    What is the goal of the study

    Our study will determine whether blood flow regulation abnormalities and abnormalities of sympathetic regulation are produced by nitric oxide and can account for splanchnic pooling in VVS and POTS. Patients will be compared to healthy control subjects. There is a detailed dietary questionnaire because diet may contribute importantly to endogenous NO. There are several autonomic questionnaires. 
    There is no treatment arm although we can easily determine dietary or medication interventions based on nitric oxide, nitrite and nitrate excess if that is determined.  If we know the specific biochemical mechanism we may be able to offer further specific treatments to specific patients. 

    Significance: Results will determine whether abnormal NO and Ang-II dependent microcirculatory
    responses, and abnormal sympathetic stress responses are present early in the course of obesity
    indicating a need for intervention long before the more pernicious effects of metabolic syndrome
    manifest.

     

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    What can your own doctor do

    We will ask for the active participation of your doctor who can rule out other illnesses that may complicate obesity. We will ask your permission and for you doctor's permission to see an adolescent medical doctor, Dr Kelly Bethea, who is participating in this study. In particular, Dr. Bethea will  perform physical examinations and tests for metabolic syndrome which are essential to the study.

    Many of the tests we will be performing are not ordinarily available to your doctor. They are, however, all approved ways of measuring how blood vessels and nerves work. The tests performed during the study may help us determine whether any specific treatment is useful for you. We will provide you and your doctor with test results and treatment information.

     

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    How do I know if I知 eligible to be in this study? 

    Inclusion: 3 or more episodes of VVS or severe presyncope within the past 12 months. Or neuropathic POTS.

    Exclusion:  Criteria for initial exclusion will include a condition known to be associated with autonomic, adrenergic, endothelial dysfunction or sympathetic nervous system abnormalities. Additional exclusion will be for any active medical condition , a previous medical condition with undocumented resolution, past or present systemic disorder. 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, 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.

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    Who pays for the exams, or testing?

    There is no charge to you for any of the the testing  directly related to this study. We will pay each participant $150 per day for their time.

     

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    How can I get a questionnaire for this study? 

    You can click on the Questionnaire icon, and download and print out the application and mail it to us. The mailing address is on the last page of the form. Alternatively you can email the application to  julian_stewart@nymc.edu or courtney_terilli@nymc.edu you can also fax us the application at 914-593-8890. Or, you can call us at 914-593-8888, leave your name and address on the voicemail and we値l mail you an application. 

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    What happens if I知 eligible to be in the study and decide to participate? 

    If you would like to take part in these studies, our research nurse coordinator, Courtney Terilli will contact you to go over questionnaire material and discuss arranging for any prior testing that may be needed. We will also arrange for certain lab testing during your time here for research purposes. Courtney  will review the consent form with you and we will also review the consent and any questions you may have when you arrive for the study. You and your parents (if applicable) should understand the study, and its risks and benefits. You can click on the icon for Consent Form to read about our study. 

    Testing lasts most of a week and you will also be asked to have a measurement of blood volume. We will make appointments to come to our center for your visits. You値l arrive at 9:30 AM on the day of your appointment. We ask that you not eat or drink anything after 6 AM that morning. Please wear comfortable clothing and bring along a pair of shorts and a short sleeve shirt. 

    We will meet you at the Bradhurst Building and take you to the laboratory area. Here you will meet our nurse coordinator Courtney Terilli, and Drs. Julian Stewart and Marvin Medow who, along with other staff, will review the study with you, and answer any questions you may have. After obtaining informed consent you値l fill out several  questionnaires, have a brief physical examination, give a urine sample, and be taken to the laboratory area.

    We will meet you at the Bradhurst Building and take you to the laboratory area. Here then you will meet Dr. Julian Stewart and Dr. Marvin Medow who, along with the Courtney will review the study with you, and answer any questions you may have. After obtaining your or your parents informed consent you値l receive several questionnaires concerning diet, syncope, autonomic illness, and be taken to the laboratory area.

    You will undergo tests of how the nerves and blood vessels function.  We will measure blood flow properties of the leg and arm vein using noninvasive techniques while lying flat. We will examine   local regulation of nitric oxide and norepinephrine made by adrenergic nerves in your skin using a technique called microdialysis and we will examine sympathetic nerve function using microneurography.

    In the first set of experiments we use Laser-Doppler flowmetry (LDF) to measure skin blood flow while lying flat. This uses a small beam of reflected light which you cannot feel. LDF will be combined with microdialysis in which we put tiny tubes called microdialysis probes within the skin of the leg using a small needle. There will be four probes placed. This will enable us to measure how much nitric oxide and  norepinephrine you make and also your response to gentle warming and to tiny amounts of norepinephrine itself.  We also will  administer small amounts of chemicals into the skin, testing the ability of the blood vessels to react normally.  The method only affects the tiny area of skin tested and has no effect on overall circulation. Thus, we can test how blood vessels work without disturbing the natural workings of the heart and circulation. We will first stimulate local blood flow in two ways: One uses gentle local heating over a small area of skin and the other uses a medication called adenosine. 
    The tests will take place on two separate days. Each day last 4 hours or so.

    On the other two days we will examine the specific dependence of the sympathetic nerves that use norepinephrine (NE) to contract your blood vessels. These are sympathetic adrenergic nerves. We will challenge your ability to release NE in response to a moderate orthostatic challenge using a well-established technique called lower body negative pressure while measuring NO and NE. We will also record how well your nerves contract to a drug, phenylephrine (neosynephrine) which stimulates  the sympathetic contraction response of blood vessels. These studies are repeated when we reduce and when we increase nitric oxide using medications. Sympathetic nerve activity is measured in a leg nerve using a tiny electrode.  There is no upright tilt involved. 

     We expect that the lab visit will take about 6 hours.

    If you have further questions about the study, please feel free to call:
    914-593-8888 for more information. 
    or Email at julian_stewart@nymc.edu

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Up
Mechanisms of Vasovagal Syncope
Local Vasoconstriction and Sympathoexcitation in Postural Tachycardia Syndrome
Brain Fog in CFS and POTS
Vascular Dysfunction in the Chronic Fatigue Syndrome
Hyperpnea in Postural Tachycardia