Sex Disparities in Hypoxic Sympatholysis and Impact of Obesity

Overview

Patients with sleep apnea are at increased risk of developing cardiovascular disease – with women at potentially greater risk than men. Contributing mechanisms are not well understood, but may be related to how women respond to low oxygen and, given over 70% of patients with sleep apnea are obese, the impact of obesity. This project seeks to increase our understanding of mechanisms that may contribute to sex differences in the cardiovascular response to low oxygen with the hope that this knowledge will improve the efficacy of current therapies and support the discovery of novel therapeutics.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 30, 2025

Interventions

  • Other: Hypoxia Exposure
    • Systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry.
  • Drug: Phenylephrine
    • Phenylephrine (0.0625 mcg/dL/min) will be locally infused via brachial artery catheter during the final 3 min of normoxia and hypoxia.
  • Drug: Dexmedetomidine
    • Dexmedetomidine (12.5 ng/dL/min) will be locally infused via brachial artery catheter during the final 3 min of normoxia and hypoxia.
  • Drug: Phentolamine
    • Phentolamine will be locally infused via brachial artery catheter for 10 min before baseline measurement (12 mcg/dL/min) and the infusion will continue at a maintenance rate (5 mcg/dL/min) during acute normoxia and hypoxia.
  • Drug: Norepinephrine
    • Regional forearm infusion at 8 ng/dL/min via brachial artery catheter during normoxia and hypoxia exposures

Arms, Groups and Cohorts

  • Experimental: Hypoxia Exposure
    • A physician will place a catheter in the brachial artery for intra-arterial pharmacological infusions. The following drugs will be administered to each participant under room air (normoxic) and low oxygen (hypoxic) conditions: phenylephrine, dexmedetomidine, norepinephrine, phentolamine (see Interventions for details).

Clinical Trial Outcome Measures

Primary Measures

  • Change in forearm vascular conductance with intra-arterial drug infusion
    • Time Frame: Continuous measurement of vascular conductance during infusion of each drug (final 3 min of normoxia and hypoxia).
    • Vascular conductance is an index of vascular tone and is measured using a technique called venous occlusion plethysmography.

Participating in This Clinical Trial

Inclusion Criteria

  • 18-45 years of age (premenopausal) – Healthy weight (BMI ≥18 and ≤25 kg/m2) – Obese (BMI ≥30 kg/m2) Exclusion Criteria:

  • Pregnancy, breastfeeding, oral hormonal contraceptive use – Diagnosed sleep apnea or Oxygen desaturation index >10 events/hr – Current smoking/Nicotine use – Increased risk of bleeding, pro-coagulant disorders, clotting disorders, anticoagulation therapy – Nerve/neurologic disease – Cardiovascular, hepatic, renal, respiratory disease – Blood pressure ≥140/90 mmHg – Diabetes, Polycystic ovarian syndrome – Communication barriers – Prescription medications, Sensitivity to lidocaine

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 45 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of Missouri-Columbia
  • Provider of Information About this Clinical Study
    • Principal Investigator: Jacqueline K Limberg, PhD, Assistant Professor – University of Missouri-Columbia
  • Overall Contact(s)
    • Jennifer L Harper, B.S., 573-882-2544, harperjl@missouri.edu

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