Clinical trial NCT04181606: Age Comparisons of Exercising Muscle O2 Supply in Healthy Adults: Effects of Esmolol Infusion
Official title: Age Comparisons of Exercising Muscle O2 Supply in Healthy Adults: Effects of Esmolol Infusion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Aging
Keywords: Esmolol hydrochloride
Exercise
Lead sponsor: Penn State University
Sponsor class: OTHER
First posted: 2019-11-29
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study will test the central hypothesis that postmenopausal women will demonstrate increased oxygen extraction in active leg muscle during leg cycling exercise while receiving an infusion of Esmolol, a fast-acting β1 selective antagonist, when compared to premenopausal women

Detailed description: This study will test the central hypothesis that postmenopausal women will demonstrate increased oxygen extraction in active leg muscle during leg cycling exercise while receiving an infusion of Esmolol, a fast-acting β1 selective antagonist, when compared to premenopausal women. β1 selective antagonists (or "β1 blockers") are used to lower heart rate and improve O2 supply-to-demand balance in patients with coronary artery disease. By using esmolol to attenuate the central sympathetic response to exercise (increased heart rate and cardiac output) we can examine peripheral mechanisms of O2 delivery. The current project will evaluate how older postmenopausal women adjust active muscle O2 supply to an acute reduction in systemic O2 delivery during large muscle dynamic exercise when compared to younger premenopausal women.

Eligibility criteria: 3.1 Inclusion Criteria

1. Capable of giving informed consent
2. Premenopausal women ages 18-35 years OR post-menopausal women ages 55-70 years
3. Satisfactory medical history and physical exam, as determined by a Clinical Research Center (CRC) clinician
4. Not currently taking medications affecting heart rate or contractility
5. Fluent in written and spoken English

3.2 Exclusion Criteria

Participants who will not be studied are those who:

1. Are less than 19 years of age or more than 70 years of age
2. Are pregnant or lactating
3. Are prisoners or institutionalized individuals or unable to consent
4. Diagnosed renal failure (Creatinine \>2.0 mg/dl)
5. Diagnosed liver disease (ALT and aspartate aminotransferase {AST} 2 times normal)
6. Diagnosed Reynaud's disease
7. Have uncontrolled diabetes
8. Have uncontrolled hypertension
9. Have a left ventricular ejection fraction \< 40%
10. Have a recent history of unstable angina or myocardial infarction (\<6 months), unstable angina, or use of nitrate medications within past 2 weeks

10. Severe lung disease (i.e., on supplemental oxygen or frequently use rescue inhalers) 11. Diagnosed bleeding or clotting disorder or recent blood transfusion 12. Have asthma, history of thyroid issues or hyperkalemia 13. Known use of recreational drugs 14. Methylphenidate use

Primary outcomes:
measure: Tissue Saturation Index (TSI) - Active Leg Muscle
timeFrame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Secondary outcomes:
measure: Tissue Saturation Index - Inactive Forearm Muscle
timeFrame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
measure: Systolic Blood Pressure
timeFrame: At rest and 3 minutes into moderate exercise and heavy exercise.
measure: Heart Rate
timeFrame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
measure: Cardiac Output
timeFrame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
measure: Diastolic Blood Pressure
timeFrame: At rest and 3 minutes into moderate exercise and heavy exercise.
measure: Mean Arterial Pressure
timeFrame: At rest and 3 minutes into moderate exercise and heavy exercise.
measure: Stroke Volume
timeFrame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
measure: Systemic Vascular Conductance
timeFrame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
measure: ∆HHb - Inactive Forearm
timeFrame: Last 60 seconds of Moderate and Heavy Exercise
Other outcomes:
Locations:
city: University Park
country: United States
facility: Noll Laboratory
state: Pennsylvania
Study officials:
References: