Reflex Responses to Intermittent Hypoxia in Humans: Mechanisms and Consequences
Condition: Sleep Apnea; Healthy; Vasoconstriction; Vasodilation
MeSH terms: Hypoxia
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The overall goal of this project is to better understand the effect of intermittent hypoxia
      (IH) on sympathetic neuronal discharge patterns in humans, as well as mechanisms that mediate
      persistent sympathoexcitation with IH.
    

Detailed description: 
      Sleep apnea is the most common form of sleep disordered breathing and patients with sleep
      apnea exhibit persistent activation of the sympathetic nervous system. Sympathoexcitation is
      also the final common pathway for a host of complications in conditions like obesity,
      hypertension, sleep apnea, and heart failure and plays a significant role in predicting
      negative clinical outcomes and deteriorating cardiovascular health. However, the mechanisms
      of sympathoexcitation with sleep apnea are poorly understood and thus make effective
      therapeutic approaches difficult to develop.

      Intermittent hypoxia (IH) has been implicated in animal models as the primary stimulus for
      evoking increases in sympathetic activity with recurrent apneas. Thus, the overall goal of
      this application is to better understand the effect of IH on sympathetic discharge patterns
      in humans as well as the mechanisms mediating persistent sympathoexcitation with IH. By
      better understanding the effect of IH on sympathoexcitation, targeted therapeutic approaches
      might be devised to mitigate the effects of sympathetic over-activity on the cardiovascular
      system in conditions such as sleep apnea.
    

Intervention name(s): Hypoxic exposure; modified Oxford test; Oral Bosentan 62.5 mg; Hypoxic ventilatory response test
Intervention type(s): Other; Other; Drug; Other
Intervention description(s): 30 minutes of intermittent hypoxia achieved using breaths of low oxygen air (5% oxygen) followed by room air through a mask.; An intravenous bolus of sodium nitroprusside (100 μg) will be given to decrease blood pressure, followed 1 minute later by a bolus of phenylephrine (150 μg) to increase blood pressure, occurring before and after intermittent hypoxia exposure.; Prior to completion of visit 2, male subjects will consume 62.5 mg twice daily for 3 days as well as the morning of the study visit (7 pills) at home and experimental sessions will be performed 3 hours after oral intake of the final dose.; Hypoxia will be achieved using breaths of low oxygen air (5% oxygen) followed by room air through a mask. This will be repeated 4-5 times per test, occurring before and after intermittent hypoxia exposure.
Intervention MeSH terms: Bosentan
Intervention model: Single Group Assignment
Intervention model description: Subjects will be asked to complete 1 1-hour screening visit, 1 overnight at-home monitoring, and 1 (women) or 2 (men) 5-hour study visits. Subjects will not be blinded to study condition and all subjects will serve as their own controls. All study visits will be separated by a minimum of 1 week and will occur at the same time of day.
Masking: None (Open Label)
Primary purpose: Basic Science