Age Comparisons of Exercising Muscle O2 Supply in Healthy Adults: Effects of Esmolol Infusion

Early Phase 1

Completed

Conditions: Aging

Interventions: Drug: Saline infusion
Drug: Esmolol infusion
Other: Pre exercise baseline
Other: Isometric handgrip exercise
Other: Semi-recumbent cycling

Registration Number: NCT04181606

Lead Sponsor: David N. Proctor, PhD

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Esmolol Infusion	Pre exercise baseline	Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Esmolol Infusion	Semi-recumbent cycling	Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Esmolol Infusion	Isometric handgrip exercise	Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Saline Infusion	Pre exercise baseline	Saline infusion volume/rate matched to the calculated dose of esmolol.
Saline Infusion	Saline infusion	Saline infusion volume/rate matched to the calculated dose of esmolol.
Saline Infusion	Isometric handgrip exercise	Saline infusion volume/rate matched to the calculated dose of esmolol.
Esmolol Infusion	Esmolol infusion	Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Saline Infusion	Semi-recumbent cycling	Saline infusion volume/rate matched to the calculated dose of esmolol.

Primary Outcome Measures

Name	Time	Method
Tissue Saturation Index (TSI) - Active Leg Muscle	Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.	The primary outcome variable is the change in skeletal muscle oxygenation (∆TSI%) in the active leg muscle from baseline during recumbent cycling using near-infrared spectroscopy. TSI% represent the percentage of oxygenated hemoglobin relative to total hemoglobin in the tissue beneath the NIRS probe. Lower values represent a greater reduction in tissue oxygenation from baseline (greater oxygen extraction and/or reduced oxygen delivery). TSI% = oxy\[heme\] / total\[heme\] x 100

Secondary Outcome Measures

Name	Time	Method
Tissue Saturation Index - Inactive Forearm Muscle	Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.	The change in skeletal muscle oxygenation (∆TSI%) in the inactive forearm from baseline during recumbent cycling using near-infrared spectroscopy. TSI% represent the percentage of oxygenated hemoglobin relative to total hemoglobin in the tissue beneath the NIRS probe. Lower values represent a greater reduction in tissue oxygenation from baseline (greater oxygen extraction and/or reduced oxygen delivery). TSI% = oxy\[heme\] / total\[heme\] x 100
Systolic Blood Pressure	At rest and 3 minutes into moderate exercise and heavy exercise.	Systolic Blood Pressure recorded via an automatic sphygmomanometer (SunTech Tango)
Heart Rate	Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.	Heart rate recorded via EKG
Cardiac Output	Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.	Cardiac Output recorded using bioimpedance cardiography
Diastolic Blood Pressure	At rest and 3 minutes into moderate exercise and heavy exercise.	Diastolic Blood Pressure recorded via an automatic sphygmomanometer (SunTech Tango)
Mean Arterial Pressure	At rest and 3 minutes into moderate exercise and heavy exercise.	Mean Arterial Pressure recorded via an automatic sphygmomanometer (SunTech Tango)
Stroke Volume	Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.	Stroke Volume recorded using bioimpedance cardiography
Systemic Vascular Conductance	Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.	Systemic Vascular Conductance recorded using bioimpedance cardiography
∆HHb - Inactive Forearm	Last 60 seconds of Moderate and Heavy Exercise	Change in deoxygenated hemoglobin (∆HHb) in the inactive forearm muscle from baseline during recumbent cycling exercise using near-infrared spectroscopy (NIRS) relative to the Total Labile Signal. ∆HHb is an index of oxygen extraction obtained using NIRS. The total labile signal is defined as the difference between the highest observed HHb value during 5 minutes of limb occlusion at 250 mmHg and the lowest observed HHb value observed during reperfusion following removal of the occlusion. Greater ∆HHb values indicate greater oxygen extraction in the tissue under the NIRS probe.