Sex Disparities in Hypoxic Sympatholysis and Impact of Obesity

Study Overview
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Brief Summary
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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.

Official Title
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Sex Disparities in Hypoxic Sympatholysis and Impact of Obesity

Conditions
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Obesity, Healthy, Vasoconstriction, Vasodilation

Intervention / Treatment
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* Other: Hypoxia Exposure
* Drug: Phenylephrine
* Drug: Dexmedetomidine
* Drug: Phentolamine
* Drug: Norepinephrine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypoxia Exposure<br>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). | Other: Hypoxia Exposure<br>* Systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry.<br>Drug: Phenylephrine<br>* Phenylephrine (0.0625 mcg/dL/min) will be locally infused via brachial artery catheter during the final 3 min of normoxia and hypoxia.<br>* Other names: Phenylephrine Hydrochloride;Drug: Dexmedetomidine<br>* Dexmedetomidine (12.5 ng/dL/min) will be locally infused via brachial artery catheter during the final 3 min of normoxia and hypoxia.<br>Drug: Phentolamine<br>* 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.<br>* Other names: Phentolamine mesylate;Drug: Norepinephrine<br>* Regional forearm infusion at 8 ng/dL/min via brachial artery catheter during normoxia and hypoxia exposures<br>|

What is the study measuring?
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Primary Outcome Measures

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