Comparing Vascular Responses to Resistance Exercise with and Without Blood Flow Restriction in Young and Older Adults

Condition(s) studied

Investigational drug(s) / intervention(s)

Low intensity-resistance training with lower limb blood flow restriction: In the LIRT-BFR, participants will perform 4 sets of 20 bilateral leg presses and knee extensions repetitions with BFR at 30% of 1-RM, with 30-second rest intervals between sets, in an estimated total of 30-minute session per participant. Cuffs will be placed in the upper thighs and inflated with a pressure that is 1.3 times the individual's ankle systolic blood pressure in the data collection day for the entirety of the training session with a commercial cuff (width×length; 11×85 cm, SC10™, Hokanson, Inc., WA, USA).

High Intensity Resistance Training: In the HIRT participants will perform bilateral leg presses and knee extension without BFR at 75% of one-repetition maximum (1-RM), for 3 sets of 10 reps, with 2-minute rest intervals, in an estimated total of 30-minute session per participant.

Study summary

Aging leads to declines in functional capacity and effort tolerance. Muscle strength remains stable from ages 25 to 50 but declines significantly after age 60, affecting activities like stair climbing and walking, reducing autonomy and independence. While muscle atrophy is a significant factor, macrovascular endothelial dysfunction also impairs skeletal muscle performance in older adults. Nitric oxide (NO), produced by endothelial cells, regulates vascular homeostasis and contractile function. NO enhances muscle fiber shortening velocity, reduces twitch time-to-peak contraction, and increases the rate of force development. Aging-related endothelial dysfunction reduces NO availability, leading to reduced muscle mass and sarcopenia via decreased skeletal muscle perfusion. Increased arterial stiffness disrupts ventricular-vascular coupling, reducing cardiac output and contributing to age-related muscle weakness. Additionally, microvascular function decreases with age, contributing to altered physical work perception and reduced function. Low capillary density is linked to reduced walking speed in older adults and reduced walking time in peripheral arterial disease patients, supporting the microvasculature\'s role in functional performance. Reduced muscle mass also increases central hemodynamic load, impacting arterial stiffness and cardiac function.

Resistance training (RT) is recommended to mitigate aging effects like loss of strength and muscle mass and reduce cardiovascular risk and all-cause mortality. Guidelines suggest 1-3 sets of 8-12 repetitions at 60-80% of the individual\'s repetition maximum (1RM), performed at least twice a week. However, older adults with osteoarthritis and cardiovascular conditions often cannot tolerate high mechanical stress and are prescribed lower intensity-resistance training (LIRT) at 40-50% of 1RM, typically yielding negligible muscle hypertrophy or strength gains. Blood flow restriction (BFR) training, which applies pressure bands to restrict blood flow during LIRT, increases muscle volume and strength. While BFR shows promise, it can cause acute increases in arterial stiffness and blood pressure in older adults, necessitating caution in its prescription.

This study aims to compare macrovascular and microvascular function responses to acute resistance exercise with and without BFR in young and older adults. We hypothesize that older adults will show a more pronounced increase in macrovascular and microvascular dysfunction following resistance exercise compared to younger participants. In this parallel group randomized controlled trial, participants will be randomly assigned to either LIRT-BFR or high-intensity resistance training (HIRT). Each participant will attend three sessions: a familiarization session and two experimental sessions involving the randomized exercise conditions. Measurements of brachial blood pressure, heart rate, and macrovascular and microvascular function will be taken at rest and during recovery periods post-exercise.

Eligibility

Primary outcome measure(s)

• Change in macrovascular function — At rest and re-evaluated 5- and 30-minutes into recovery following the experimental conditions
  We will use the slowing of the pulse wave velocity (PWV) recorded between the upper arm and the wrist as an index of macrovascular function. PWV is inversely related to arterial distensibility; a widening of the brachial artery cross-section will cause a drop in post-occlusive PWV. Macrovascular function will be evaluated using EndoFMS (Vicorder, Berlin, Germany), and the response parameters are PWVmin and PWV% change from pre-occlusion values. The percentage change from initial PWV is called FMS. The default cuff placement is a 10 cm brachial cuff on the upper arm and a 7 cm wrist cuff on the selected limb. The test is performed with the patient lying horizontally, the right arm extended at a 60-degree angle, and the hand rotated palm up. After the patient relaxes, the test starts with a target occlusion pressure 30 mmHg above systolic pressure. Brachial PWV is measured between the wrist and upper arm over 10 minutes, with a 5-minute occlusion period.
• Change in central arterial stiffness — At rest and re-evaluated 5- and 30-minutes into recovery following the exercise condition
  To measure arterial stiffness, we will assess carotid-femoral pulse wave velocity (cPWV) using a Vicorder module (Berlin, Germany). Participants will be in a reclined position, with a minimum of 10 minutes of rest. A 100 mm blood pressure cuff will encircle the upper thigh, and a 30 mm partial cuff will be applied around the neck at the level of the carotid arteries, above the thyroid prominence. The direct path length will be measured from the suprasternal angle to the middle of the femoral blood pressure cuff by the same operator. Both cuffs will be simultaneously inflated to 60 mm Hg to capture femoral and carotid waveforms. Continuous recordings will be obtained beat-to-beat for at least 3 minutes. Automated software will determine the wave\'s foot using an intersecting tangent algorithm. The time delay between the foot of the carotid and femoral waveforms will provide the average TT every 3.5 seconds.
• Change in blood pressure — at rest and re-evaluated after each set and 5- and 30-minutes into recovery following the exercise condition
  The brachial artery pulse waveform obtained oscillometrically, will be analyzed using the Pulse Wave Analysis (PWA) function of the Vicorder® device (Berlin, Germany), and the aortic waveform calculated using a transfer function. This enables calculation of arterial system parameters, including cSBP, augmentation pressure (AugPress), augmentation index (AugInd), central peripheral pressure (cPP), cardiac output, and total peripheral resistance. Initial waves will be omitted, and good-quality consecutive pulse waves will be analyzed.
• Change in microvascular function — At rest and re-evaluated 5- and 30-minutes into recovery following the exercise condition
  Microvascular function will be assessed using EndoPAR (Vicorder, Berlin, Germany). Participants will be in a supine position with their arms comfortably positioned. Changes in the peripheral arterial dilation ratio (PAR) signal to reactive hyperemia (RH) will be measured at the fingertip with photoplethysmographs and an inflating device controlled by a computer algorithm. The RH procedure consists of a 30-second calibration, a 5-minute baseline recording, followed by 5 minutes of blood flow occlusion of the test arm using an upper arm blood pressure cuff inflated to 30 mmHg above the patient's systolic brachial pressure. After cuff deflation, the PAR tracing will be recorded for another 3 minutes. The software automatically normalizes this ratio to the concurrent signal from the contralateral, non-occluded forearm to correct for confounding variables. This ratio is then multiplied with a baseline correction factor to obtain Measured Peak, Max Reference Peak, and Max PAR.

Trial sites (2)

More Egas Moniz - Cooperativa de Ensino Superior, CRL trials in Portugal

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