Circulatory Dysfunction in Chronic Fatigue Syndrome

Summary

Principal Investigator: Julian Stewart
Abstract: DESCRIPTION: Chronic fatigue syndrome (CFS) is associated with orthostatic intolerance which often takes the form of postural orthostatic tachycardia syndrome (POTS) in adolescents. Preliminary data suggest the novel concept that defective vasoconstriction produces POTS in CFS with cardiac autonomic changes as a secondary response. CFS patients will be compared to healthy controls and to controls with simple faints to test 3 hypotheses: 1) Blood is redistributed peripherally and redistribution is enhanced during orthostasis producing increased microvascular filtration and dependent edema. Central hypovolemia causes decreased cardiac output, reflex tachycardia and reduced cerebral blood flow. This is enhanced during orthostasis producing increased microvascular filtration, dependent edema, and peripheral pooling. These changes alter the interstitium, and cause reflex tachycardia, reduced cerebral blood flow and often hypotension. Blood volume and cardiac output using the indocyanine green dye dilution technique will be measured supine, during conventional 700 head-up tilt, and during low angle head-up tilt. Cerebral blood flow velocity (CBFv) will be estimated by transcranial Doppler ultrasonography. Thoracic, splanchnic, and pelvic vascular volumes will be measured by impedance plethysmography, and limb blood flow, arterial flow, venous volume-pressure relation, and venous pressure will be measured by venous occlusion strain gauge plethysmography. These will show increased blood flow to lower extremities when upright. Central hypovolemia will occur and will reduce CBF and produce symptoms of CFS. Cardiac autonomic status including baroreflex will be assessed by heart rate and blood pressure variability and transfer function. Baroreflex and heart rate variability will be decreased and blood pressure variability will be increased related to circulatory deficit 2) The defect in vasoconstriction is heterogeneous comprising abnormal arterial baroreflex mediated sympathetic vasoconstriction in one subgroup of CFS patients and abnormal local vasoconstriction in a second subgroup with defective veno-arteriolar reflex (arterial baroreflex insensitive dysfunction). Low angle tilt will be used to activate baroreflex mediated and local reflexes. Local reflexes including myogenic, metabolic and veno-arteriolar will be sorted out through use of supine testing designed to specifically stimulate a specific reflex (limb hang, large pressure step and reactive hyperemia) and measuring peripheral resistance. 3) Cardiac autonomic findings are secondary to circulatory changes. Thus, tachycardia relates to vagal withdrawal because of circulatory insufficiency. CFS patients will be treated with midodrine or placebo in a cross-over study. Using supine and low angle tilt experiments, circulatory measurements and psychological instruments will be combined to demonstrate that circulatory abnormalities, autonomic abnormalities and symptoms correct in a subgroup of CFS patients with low resting peripheral resistance.
Funding Period: 2001-08-24 - 2006-07-31
more information: NIH RePORT

Top Publications

  1. pmc Initial orthostatic hypotension in the young is attenuated by static handgrip
    Debbie A Clarke
    Department of Pediatrics, The Center for Hypotension, New York Medical College, Valhalla, NY, USA
    J Pediatr 156:1019-22, 1022.e1. 2010
  2. pmc Increased pulsatile cerebral blood flow, cerebral vasodilation, and postsyncopal headache in adolescents
    Anthony J Ocon
    Department of Physiology, Center for Hypotension, New York Medical College, Valhalla, NY, USA
    J Pediatr 159:656-62.e1. 2011
  3. pmc Postural change alters autonomic responses to breath-holding
    Indu Taneja
    Department of Pediatrics, New York Medical College, Valhalla, NY, USA
    Clin Auton Res 20:65-72. 2010
  4. pmc Increased vasoconstriction predisposes to hyperpnea and postural faint
    Indu Taneja
    Department of Pediatrics, New York Medical College, Hawthorne, NY 10532, USA
    Am J Physiol Heart Circ Physiol 295:H372-81. 2008
  5. ncbi Angiotensin II type 1 receptor blockade corrects cutaneous nitric oxide deficit in postural tachycardia syndrome
    Julian M Stewart
    The Center for Pediatric Hypotension, New York Medical College, 19 Bradhurst Avenue, Hawthorne, NY 10532, USA
    Am J Physiol Heart Circ Physiol 294:H466-73. 2008
  6. ncbi Reduced central blood volume and cardiac output and increased vascular resistance during static handgrip exercise in postural tachycardia syndrome
    Julian M Stewart
    Department of Pediatrics, New York Medical College, Valhalla, New York, USA
    Am J Physiol Heart Circ Physiol 293:H1908-17. 2007
  7. ncbi Changes in regional blood volume and blood flow during static handgrip
    Julian M Stewart
    Professor of Pediatrics and Physiology, Research Division and Hypotension Laboratory, New York Medical College, Suite 3050, 19 Bradhurst Ave, Hawthorne, NY 10532, USA
    Am J Physiol Heart Circ Physiol 292:H215-23. 2007
  8. ncbi Laser Doppler flowmetry detection of endothelial dysfunction in end-stage renal disease patients: correlation with cardiovascular risk
    A Kruger
    Department of Medicine, New York Medical College, Valhalla, New York 10595, USA
    Kidney Int 70:157-64. 2006
  9. ncbi Postural hypocapnic hyperventilation is associated with enhanced peripheral vasoconstriction in postural tachycardia syndrome with normal supine blood flow
    Julian M Stewart
    Department of Pediatrics, Research Division and Hypotension Laboratory, New York Medical College, Suite 3050, 19 Bradhurst Ave, Hawthorne, NY 10532, USA
    Am J Physiol Heart Circ Physiol 291:H904-13. 2006
  10. ncbi Increased plasma angiotensin II in postural tachycardia syndrome (POTS) is related to reduced blood flow and blood volume
    Julian M Stewart
    Center for Pediatric Hypotension, New York Medical College, Valhalla, NY 10595, USA
    Clin Sci (Lond) 110:255-63. 2006

Scientific Experts

  • Julian Stewart
  • Indu Taneja
  • Marvin S Medow
  • Anthony J Ocon
  • Debbie A Clarke
  • A Kruger
  • Zachary Messer
  • R Garrick
  • C Thompson
  • M S Goligorsky
  • E O'Riordan
  • P Vallance
  • S Adler
  • R Sahityani
  • Christopher T Minson

Detail Information

Publications16

  1. pmc Initial orthostatic hypotension in the young is attenuated by static handgrip
    Debbie A Clarke
    Department of Pediatrics, The Center for Hypotension, New York Medical College, Valhalla, NY, USA
    J Pediatr 156:1019-22, 1022.e1. 2010
    ..We show that in 14 subjects with initial orthostatic hypotension, isometric handgrip coupled with standing abolished symptoms of initial orthostatic hypotension and minimized decreases in blood pressure and cardiac output with standing...
  2. pmc Increased pulsatile cerebral blood flow, cerebral vasodilation, and postsyncopal headache in adolescents
    Anthony J Ocon
    Department of Physiology, Center for Hypotension, New York Medical College, Valhalla, NY, USA
    J Pediatr 159:656-62.e1. 2011
    ....
  3. pmc Postural change alters autonomic responses to breath-holding
    Indu Taneja
    Department of Pediatrics, New York Medical College, Valhalla, NY, USA
    Clin Auton Res 20:65-72. 2010
    ..We used breath-holding during inspiration as a model to study the effect of pulmonary stretch on sympathetic nerve activity...
  4. pmc Increased vasoconstriction predisposes to hyperpnea and postural faint
    Indu Taneja
    Department of Pediatrics, New York Medical College, Hawthorne, NY 10532, USA
    Am J Physiol Heart Circ Physiol 295:H372-81. 2008
    ..Hyperpnea and pulmonary stretch may contribute to the sympathoinhibition that occurs at the time of faint...
  5. ncbi Angiotensin II type 1 receptor blockade corrects cutaneous nitric oxide deficit in postural tachycardia syndrome
    Julian M Stewart
    The Center for Pediatric Hypotension, New York Medical College, 19 Bradhurst Avenue, Hawthorne, NY 10532, USA
    Am J Physiol Heart Circ Physiol 294:H466-73. 2008
    ..53 +/- 2 %CVC(max)). The data suggest that the reduction in cutaneous NO-dependent vasodilation in low-flow POTS is corrected by AT(1)R blockade...
  6. ncbi Reduced central blood volume and cardiac output and increased vascular resistance during static handgrip exercise in postural tachycardia syndrome
    Julian M Stewart
    Department of Pediatrics, New York Medical College, Valhalla, New York, USA
    Am J Physiol Heart Circ Physiol 293:H1908-17. 2007
    ..While increased cardiac output and central blood volume characterizes controls, increased peripheral resistance with blunted or eliminated in central blood volume increments characterizes POTS and may contribute to exercise intolerance...
  7. ncbi Changes in regional blood volume and blood flow during static handgrip
    Julian M Stewart
    Professor of Pediatrics and Physiology, Research Division and Hypotension Laboratory, New York Medical College, Suite 3050, 19 Bradhurst Ave, Hawthorne, NY 10532, USA
    Am J Physiol Heart Circ Physiol 292:H215-23. 2007
    ..We conclude that the exercise pressor reflex is associated with reduced baroreflex cardiovagal regulation and driven by increased cardiac output related to enhanced preload, cardiac contractility, and splanchnic blood mobilization...
  8. ncbi Laser Doppler flowmetry detection of endothelial dysfunction in end-stage renal disease patients: correlation with cardiovascular risk
    A Kruger
    Department of Medicine, New York Medical College, Valhalla, New York 10595, USA
    Kidney Int 70:157-64. 2006
    ..In conclusion, LDF parameters of microvascular reactivity offer a sensitive characterization of endothelial dysfunction, which may improve CV risk assessment through incorporation into the Framingham or Cardiorisk algorithm...
  9. ncbi Postural hypocapnic hyperventilation is associated with enhanced peripheral vasoconstriction in postural tachycardia syndrome with normal supine blood flow
    Julian M Stewart
    Department of Pediatrics, Research Division and Hypotension Laboratory, New York Medical College, Suite 3050, 19 Bradhurst Ave, Hawthorne, NY 10532, USA
    Am J Physiol Heart Circ Physiol 291:H904-13. 2006
    ..Variability indexes suggested enhanced sympathetic activation in POTS(HC) compared with other subjects. The data suggest enhanced cardiac and peripheral sympathetic excitation in POTS(HC)...
  10. ncbi Increased plasma angiotensin II in postural tachycardia syndrome (POTS) is related to reduced blood flow and blood volume
    Julian M Stewart
    Center for Pediatric Hypotension, New York Medical College, Valhalla, NY 10595, USA
    Clin Sci (Lond) 110:255-63. 2006
    ..The data suggest that plasma Ang II is increased in low-flow POTS patients with hypovolaemia, which may contribute to local blood flow dysregulation and reduced NO bioavailability...
  11. ncbi Decreased microvascular nitric oxide-dependent vasodilation in postural tachycardia syndrome
    Marvin S Medow
    New York Medical College, Valhalla, NY, USA
    Circulation 112:2611-8. 2005
    ..One variant of postural tachycardia syndrome (POTS), designated low-flow POTS, is associated with decreased peripheral blood flow related to impaired local vascular regulation...
  12. ncbi Persistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome
    Julian M Stewart
    Department of Pediatrics, New York Medical College, Valhalla, NY, USA
    Am J Physiol Heart Circ Physiol 290:H665-73. 2006
    ..Lower body vasoconstriction in high-flow POTS was abnormal, and vasoconstriction in low-flow POTS was sustained at initially elevated supine levels...
  13. ncbi Splanchnic hyperemia and hypervolemia during Valsalva maneuver in postural tachycardia syndrome
    Julian M Stewart
    Department of Pediatrics, New York Medical College, Valhalla, NY, USA
    Am J Physiol Heart Circ Physiol 289:H1951-9. 2005
    ..Thus splanchnic hyperemia and hypervolemia are related to excessive phase II blood pressure reduction in POTS despite intense peripheral vasoconstriction. Factors other than autonomic dysfunction may play a role in POTS...
  14. ncbi Plantar vibration improves leg fluid flow in perimenopausal women
    Julian M Stewart
    Depts of Pediatrics and Physiology, The Center for Pediatric Hypotension and Division of Pediatric Cardiology, Suite 618, Munger Pavilion, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Regul Integr Comp Physiol 288:R623-9. 2005
    ....
  15. ncbi Reciprocal splanchnic-thoracic blood volume changes during the Valsalva maneuver
    Julian M Stewart
    Department of Pediatrics, New York Medical College, Valhalla, New York 10595, USA
    Am J Physiol Heart Circ Physiol 288:H752-8. 2005
    ..Changes in baseline splanchnic vascular properties may account for variability in thoracic blood volume changes during the Valsalva maneuver...