Vascular Dysfunction in the Chronic Fatigue Syndrome


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 ]

 Up ] Screening page Open in Circulatory Dysfunction in CFS ] Contact ] Consent page Open in Circulatory Dysfunction in CFS ]


    Welcome to the CFS Circulatory Study website. Researchers at the Center for Pediatric Hypotension at New York Medical College in Valhalla NY have received funding from the National Institutes of Health (NIH) to study whether circulatory problems explain the symptoms and signs of the chronic fatigue syndrome in teenagers..

    The Principal Investigator for this study is Julian M. Stewart  MD, PhD, Professor of Pediatrics and of Physiology at  New York Medical College.

    What comprises the study population? 
    What is the hypothesis and importance of the study?
    What are the symptoms and findings in patients?
    What is the goal of the study?
    What your own doctor can do to help diagnose CFS.
    How do I know if I知 eligible to be in this study? 
    Who pays for the exams, testing, and travel? 
    How can I get a screening application for this study? 
    If I decide to participate what does the study entail?


    What comprises the study population? 

    We are seeking patients aged 15-29 years old patients with chronic fatigue syndrome (CFS) with or without any overt form of cardiovascular or circulatory disease. While many young people with CFS have a form of overt chronic orthostatic intolerance (the inability to remain upright without symptoms) there are many others who do not. Yet the latter group may still have abnormalities of the small blood vessels, also called microvessels, that are most important in the regulation of blood volume and blood flow.  Thus, some of the CFS patients have symptoms of chronic orthostatic intolerance such as  dizziness, nausea, headache, pallor, and neurocognitive loss (difficulty thinking) which overlap with the case definition of CFS. Others may not have obvious symptoms while standing but might still have blood vessel abnormalities (i.e. vascular dysfunction) that contribute to fatigue and might benefit from specific therapy.


    What is the hypothesis and importance

    Blood flow abnormalities associated with the postural tachycardia syndrome (POTS) produce major disability in younger chronic fatigue syndrome (CFS) patients. These may be due to defects in a fundamental signaling molecule called nitric oxide (NO) or in its interaction with another molecule called angiotensin. In the current proposal we will determine how NO and angiotensin produce POTS in CFS patients and whether drugs that alter NO and angiotensin can improve patient health.

    We will subset CFS patients by POTS using upright tilt, and subgroup POTS based on noninvasive measurements of peripheral blood flow. Some patients who we denote low flow CFS/POTS have reduced peripheral blood flow, while others have normal flow.
    We will determine whether low flow CFS/POTS is due to decreased NO produced by nNOS and related to increased angiotensin-II (A-II) and oxidative stress.  We will measure skin blood flow with lasers, and NO and angiotensin by intradermal microdialysis tiny tubes in the skin), and use local heating and chemical responses in the skin to a commonly used blocker of angiotensin called losartan. If losartan works in the skin we will try to treat low blood flow with oral losartan and measure the extent of improvement in blood flow throughout your body.

    Data suggest that NO is increased in normal flow CFS/POTS at least in the gut circulation causing pooling of blood during upright posture. We will determine whether this is true in the skin. If this is true in the skin, we will test whether a systemic medication called octreotide reduces orthostatic gut blood  pooling and cutaneous microvascular NO dependent responses.


    What are the symptoms of CFS with POTS

     Fainting is uncommon. Symptoms of CFS/POTS and chronic orthostatic intolerance including dizziness, fatigue, nausea and abdominal pain, headache, pallor, and neurocognitive loss (difficulty thinking), shakiness and exercise intolerance which overlap with the case definition of CFS. Most of the time these symptoms are postural, present mostly when upright or standing and relieved by lying down.



    What is the goal of the study

    The overall objective of the current application is to determine the biochemical mechanisms of CFS/POTS as they relate to changes in  NO and angiotensin, and to explore the possibility of subclinical, microvascular abnormalities in those CFS patients without POTS. If POTS is present we will also test medications used for treating POTS which may help teenagers with CFS.


    What can your own doctor do

    Your doctor can rule out other illnesses such as infectious and inflammatory conditions which can produce similar symptoms. For example, most blood tests will be performed by your own physician. However, the tests we will be performing are not ordinarily available to your doctor. They are, however, all approved ways of measuring how blood vessels work. POTS can be treated by a combination of lifestyle adjustments and medication which your doctor can administer. The tests performed during the study may help us determine what treatment is best for you. We will provide you and your doctor with test results and treatment information.



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

    Even though the study focuses on CFS patients with vascular dysfunction, all CFS patients should enroll. At this time we cannot predict who has circulatory dysfunction or if POTS is the only form of orthostatic intolerance in young persons with CFS. Therefore all patients who fulfill the criteria for CFS (using the 1994 Centers for Disease Control definition) and are between 15 and 29 years old can enroll.

    The diagnosis of CFS should be made by a doctor, either your own physician or through contact with our center.

    Exclusion:The criteria for initial exclusion are adapted from the CDC  and include: 1) an active medical condition that may explain the diagnosis; 2) a previous medical condition with undocumented resolution; 3) a past or current major psychiatric disorder; 4) a history of alcohol or substance abuse within 2 years before the onset of the chronic fatigue.

    Inclusion: The criteria for initial inclusion are adapted from the CDC:15 and 29 years old adolescents who have persistent or relapsing chronic fatigue of new or definite onset; and the concurrent occurrence of four or more of the following symptoms that have persisted or recurred during at least 6 consecutive months and have not predated the fatigue:
    1) impairment in memory or concentration severe enough to cause substantial reduction of previous levels of educational, social or personal activities. In adolescents this may be most notable by a decline in academic performance and school attendance;
    2) muscle pain or multi joint pain;
    3) headaches of a new type, pattern, or severity;
    4) unrefreshing sleep; and
    5) post-exertional malaise lasting more than 24

    Sore throat and swollen glands are unreliable criteria during adolescence .



    Who pays for the exams, or testing?

    There is no charge to you for any of the the testing or testing medication. We will pay each participant who $300 as a token of appreciation for their time.



    How can I get a screening application for this study? 

    You can click on the Screening 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 or to or you can also fax us the application at 914-593-8888. 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. 


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

    If you would like to take part in this study, Courtney Terilli, our nurse research coordinator, will contact you to go over questionnaire material and discuss arranging for the study. The study nurse 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 should understand the study, and its risks and benefits. You can click on the icon for Consent Form to read about our study.  If it is at all possible patients should not be taking medications that could affect the results. These might include beta blockers, fludrocortisone, and other medications that affect blood vessel or cardiac function. You must work with your doctor to see if this is safe to do and to determine how it is best accomplished.

    Testing will last 2 days. We will make an appointment to come to The Center for Hypotension for your study visits. You値l arrive at 9:00-10 AM on the first day of your appointment. We ask that you not eat or drink anything after 8 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 the you will meet Drs. Stewart, Taneja and Medow  who, along with the nurse, will review the study with you, and answer any questions you may have. After obtaining your or your parents informed consent ,  you値l  be taken to the laboratory area.

    Patients will undergo most studies of blood flow while lying down. A tilt test may be necessary on the first day of testing.  Medication will be administered on the second day of testing and responses assessed while lying down and during a sshort tilt test. Tilt tests will last a maximum of 10 minutes and will involve no faint-provoking medications. Simple tests of how the nervous system adjusts to changes in circulation will also be performed. We will also measure blood hormone levels. Most likely you will be asked to have a measurement of blood volume using the FDA approved Daxor method which can be done near your home.

    If medication appears to have an acute benefit we will issue a prescription for home use.

    We believe that this study will help to determine the specific cause of POTS in CFS and will point towards improved medical therapy for younger CFS patients.

     We expect that each visit will last about 6 hours.

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




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