Gender & orthostatic intolerance: mechanisms and therapy

Summary

Principal Investigator: Qi Fu
Abstract: DESCRIPTION (provided by applicant): The global objective of this Mentored Patient-Oriented Research Career Development Award is to build my career as an academic physician-scientist and make the transition to become an independent investigator. To accomplish this goal, together with my mentor, i have developed a tightly integrated plan including cutting edge science, and advanced training in the techniques of patient-oriented research. By participating in the K30 Curriculum in Patient-Oriented Research at UT Southwestern leading towards a MPH degree, I will receive in-depth instruction in research design, protection of human subjects, grantsmanship, and advanced level biostatistics. From my mentor and advisory committee, made up of senior scientists both at UT Southwestern and at the Brigham and Women's Hospital, I also will acquire critical new research skills regarding renal/neurohormonal mechanisms of blood pressure control, reproductive endocrinology, and clinical orthostatic intolerance. My research plan focuses on the mechanisms underlying gender differences in orthostatic tolerance, including neurohumoral influences on cardiovascular control processes and physical characteristics (primarily cardiac size and function) that determine orthostatic distribution of central blood volume. Menstrual cycle variability in young women, and differences among men, women, and women with chronic orthostatic intolerance (Postural Orthostatic Tachycardia Syndrome, or "POTS") will be examined. Finally, a specific intervention (exercise training) will be studied as treatment for patients with POTS and compared with standard pharmacologic therapies (13-blockers and volume expanders). Autonomic neural control of hemodynamic and sympathetic responses to the Valsalva maneuver, static handgrip, a cold pressor test, and prolonged head-up tilt will be investigated; the venoarteriolar response and neurohumoral responses to a long-term standing will be examined. After completion of the proposed project, we will know whether gender-specific factors such as the menstrual cycle or physical factors influencing cardiac size and function are among the determinants for orthostatic intolerance in young women, and whether physical exercise training can be considered an effective non-pharmacologic treatment for patients to improve their orthostatic tolerance. The combination of advanced training in patient-oriented research and in-depth study of an important clinical problem will prepare me well for a career as an independent investigator.
Funding Period: 2004-04-15 - 2009-03-31
more information: NIH RePORT

Top Publications

  1. pmc Vasomotor sympathetic neural control is maintained during sustained upright posture in humans
    Qi Fu
    Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, University of Texas Southwestern Medical Center at Dallas, TX 75231, USA
    J Physiol 577:679-87. 2006
  2. pmc Short-term exercise training improves the cardiovascular response to exercise in the postural orthostatic tachycardia syndrome
    Shigeki Shibata
    Institute for Exercise and Environmental Medicine, 7232 Greenville Avenue, Suite 435, Dallas, TX 75231, USA
    J Physiol 590:3495-505. 2012
  3. pmc Cardiac output and sympathetic vasoconstrictor responses during upright tilt to presyncope in healthy humans
    Qi Fu
    Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, TX 75231, USA
    J Physiol 590:1839-48. 2012
  4. pmc Exercise training versus propranolol in the treatment of the postural orthostatic tachycardia syndrome
    Qi Fu
    Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, 7232 Greenville Ave, Suite 435, Dallas, TX 75231, USA
    Hypertension 58:167-75. 2011
  5. pmc Sex differences in the modulation of vasomotor sympathetic outflow during static handgrip exercise in healthy young humans
    Sara S Jarvis
    Institute for Exercise and Environmental Medicine, 7232 Greenville Ave, Suite 435, Dallas, TX 75231, USA
    Am J Physiol Regul Integr Comp Physiol 301:R193-200. 2011
  6. pmc Cardiac origins of the postural orthostatic tachycardia syndrome
    Qi Fu
    Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas 75231, USA
    J Am Coll Cardiol 55:2858-68. 2010
  7. pmc Menstrual cycle affects renal-adrenal and hemodynamic responses during prolonged standing in the postural orthostatic tachycardia syndrome
    Qi Fu
    Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Tex 75231, USA
    Hypertension 56:82-90. 2010
  8. pmc Autonomic circulatory control during pregnancy in humans
    Qi Fu
    Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, Dallas, TX 75231, USA
    Semin Reprod Med 27:330-7. 2009
  9. pmc Menstrual cycle effects on sympathetic neural responses to upright tilt
    Qi Fu
    Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, Dallas, TX 75231, USA
    J Physiol 587:2019-31. 2009
  10. pmc Neural and nonneural mechanisms for sex differences in elderly hypertension: can exercise training help?
    Qi Fu
    Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, Dallas, TX 75231, USA
    Hypertension 52:787-94. 2008

Detail Information

Publications11

  1. pmc Vasomotor sympathetic neural control is maintained during sustained upright posture in humans
    Qi Fu
    Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, University of Texas Southwestern Medical Center at Dallas, TX 75231, USA
    J Physiol 577:679-87. 2006
    ..e. 45 min) orthostasis without obvious changes in vasomotor sympathetic neural control...
  2. pmc Short-term exercise training improves the cardiovascular response to exercise in the postural orthostatic tachycardia syndrome
    Shigeki Shibata
    Institute for Exercise and Environmental Medicine, 7232 Greenville Avenue, Suite 435, Dallas, TX 75231, USA
    J Physiol 590:3495-505. 2012
    ..023). There were no changes in any Doppler index after training. These results suggest that short-term exercise training improves physical fitness and cardiovascular responses during exercise in patients with POTS...
  3. pmc Cardiac output and sympathetic vasoconstrictor responses during upright tilt to presyncope in healthy humans
    Qi Fu
    Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, TX 75231, USA
    J Physiol 590:1839-48. 2012
    ..However, an intrinsic impairment of vasomotor responsiveness and sympathetic baroreflex function is not the cause of neurally mediated (pre)syncope in this population...
  4. pmc Exercise training versus propranolol in the treatment of the postural orthostatic tachycardia syndrome
    Qi Fu
    Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, 7232 Greenville Ave, Suite 435, Dallas, TX 75231, USA
    Hypertension 58:167-75. 2011
    ..63; 39±7 versus 39±5, P=0.73). These results suggest that, for patients with POTS, exercise training is superior to propranolol at restoring upright hemodynamics, normalizing renal-adrenal responsiveness, and improving quality of life...
  5. pmc Sex differences in the modulation of vasomotor sympathetic outflow during static handgrip exercise in healthy young humans
    Sara S Jarvis
    Institute for Exercise and Environmental Medicine, 7232 Greenville Ave, Suite 435, Dallas, TX 75231, USA
    Am J Physiol Regul Integr Comp Physiol 301:R193-200. 2011
    ..Women demonstrated a blunted metaboreflex, unaffected by sex hormones, which may be due to differences in muscle mass or fiber type and, therefore, metabolic stimulation of group IV afferents...
  6. pmc Cardiac origins of the postural orthostatic tachycardia syndrome
    Qi Fu
    Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas 75231, USA
    J Am Coll Cardiol 55:2858-68. 2010
    ..The purpose of this study was to test the hypothesis that a small heart coupled with reduced blood volume contributes to the postural orthostatic tachycardia syndrome (POTS) and that exercise training improves this syndrome...
  7. pmc Menstrual cycle affects renal-adrenal and hemodynamic responses during prolonged standing in the postural orthostatic tachycardia syndrome
    Qi Fu
    Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Tex 75231, USA
    Hypertension 56:82-90. 2010
    ..The high estrogen and progesterone in the MLP are associated with greater increases in renal-adrenal hormones and presumably more volume retention, which improve late-standing tolerance in these patients...
  8. pmc Autonomic circulatory control during pregnancy in humans
    Qi Fu
    Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, Dallas, TX 75231, USA
    Semin Reprod Med 27:330-7. 2009
    ....
  9. pmc Menstrual cycle effects on sympathetic neural responses to upright tilt
    Qi Fu
    Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, Dallas, TX 75231, USA
    J Physiol 587:2019-31. 2009
    ..Thus, other factors rather than sympathetic baroreflex control mechanisms contribute to sex differences in orthostatic tolerance in young humans...
  10. pmc Neural and nonneural mechanisms for sex differences in elderly hypertension: can exercise training help?
    Qi Fu
    Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, Dallas, TX 75231, USA
    Hypertension 52:787-94. 2008
  11. pmc Ovarian cycle and sympathoexcitation in premenopausal women
    Jason R Carter
    Department of Kinesiology and Integrative Physiology, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA
    Hypertension 61:395-9. 2013
    ..This dynamic interaction among E(2), P, and MSNA likely explains previously reported inconsistencies in the field; it remains possible that other sex steroids, such as testosterone, might explain further variance...