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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
30
The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).
Saline will be rate/volume matched to the calculated esmolol dose.
Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Noll Laboratory
University Park, Pennsylvania, United States
Tissue Saturation Index (TSI) - Active Leg Muscle
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
Time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Tissue Saturation Index - Inactive Forearm Muscle
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
Time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Systolic Blood Pressure
Systolic Blood Pressure recorded via an automatic sphygmomanometer (SunTech Tango)
Time frame: At rest and 3 minutes into moderate exercise and heavy exercise.
Heart Rate
Heart rate recorded via EKG
Time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Cardiac Output
Cardiac Output recorded using bioimpedance cardiography
Time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
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The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
Diastolic Blood Pressure
Diastolic Blood Pressure recorded via an automatic sphygmomanometer (SunTech Tango)
Time frame: At rest and 3 minutes into moderate exercise and heavy exercise.
Mean Arterial Pressure
Mean Arterial Pressure recorded via an automatic sphygmomanometer (SunTech Tango)
Time frame: At rest and 3 minutes into moderate exercise and heavy exercise.
Stroke Volume
Stroke Volume recorded using bioimpedance cardiography
Time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Systemic Vascular Conductance
Systemic Vascular Conductance recorded using bioimpedance cardiography
Time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
∆HHb - Inactive Forearm
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.
Time frame: Last 60 seconds of Moderate and Heavy Exercise