Effects of Age, Sex and Isometric Exercise on Ventricular-Vascular Interactions During Cardiac Unloading

NCT06939153 | Recruiting

• 1 other identifier: 4001
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

As people get older, especially women, they often feel dizzy or even faint when they go from sitting or lying down to standing up. This happens because their blood pressure (BP) drops, which can lead to falls, heart problems, and even death in older adults. When BP changes, it affects how well the heart works and how it talks with blood vessels. However, little research has been done on how the heart and blood vessels talk during times of low BP. The crosstalk between the heart and blood vessels is important, as it allows enough blood and oxygen to reach the brain and other vital organs. Some research shows that as we get older, the crosstalk does not work as well. This can make it harder for blood to flow properly or put extra pressure on the heart and arteries. That's why we want to study how the heart and blood vessels talk during a laboratory-simulated situation of low BP in young and older men and women. In our study, participants will lie down with their lower body in a chamber that creates a vacuum around their legs. This safely mimics what happens when you stand up quickly. We can then measure heart function, the stress on arteries, and BP while your legs are in that vacuum. We'll use an ultrasound to check the heart and a finger cuff to measure BP. We'll also see if gripping something firmly can help protect from sudden drops in blood pressure. This study will help us understand more about a condition called orthostatic hypotension and might even suggest that handgrip exercise could prevent it. The main questions the current study aims to address are:

• Does the cross-talk between the heart and vessels become more impaired with aging during laboratory-simulated conditions of low BP?
• Do women have worse crosstalk between the heart and blood vessels during laboratory-simulated conditions of BP?
• Does hand gripping protect against drops in BP during conditions of low BP? All participants will be asked to
• Complete two laboratory conditions on two separate days with a randomized order (like flipping a coin):
• Exposure to a lower body negative pressure (LBNP) chamber to safely simulate low BP (control)
• Exposure to a lower body negative pressure (LBNP) while conducting hand-squeezingexercise (experimental). The investigators will examine how heart and blood vessel interactions, as well as blood pressure (BP) responses, differ in young and older adults of both sexes when exposed to a laboratory-simulated low BP condition (LBNP), both with and without hand squeezing exercise.

Conditions

Orthostatic Intolerance

Outcome Measures

Primary Outcomes (5)

• Arterial elastance

  Arterial elastance reflective of lumped afterload will be non-invasively estimated as end-systolic pressure (obtained from tonometry) divided by stroke volume (obtained from echocardiography)

  "Baseline/pre-LBNP", "During each LBNP stage (-20 mmHg, -30 mmHg, -40 mmHg, -50 mmHg) in the last 2 minutes"

• Ventricular elastance

  Ventricular elastance, reflective of ventricle contractility, will be non-invasively estimated as end-systolic pressure (obtained from tonometry) divided by end-systolic volume (obtained from echocardiography).

  "Baseline/pre-LBNP", "During each LBNP stage (-20 mmHg, -30 mmHg, -40 mmHg, -50 mmHg) in the last 2 minutes"

• Ventricular-vascular coupling ratio

  The arterial-to-ventricular elastance ratio will be considered as an index describing cardiac energy and efficacy.

  "Baseline/pre-LBNP", "During each LBNP stage (-20 mmHg, -30 mmHg, -40 mmHg, -50 mmHg) in the last 2 minutes"

• Wasted pressure effort

  Wasted pressure effort, a marker of pulsatile afterload, will be estimated from pressure-flow analyses

  "Baseline/pre-LBNP", "During each LBNP stage (-20 mmHg, -30 mmHg, -40 mmHg, -50 mmHg) in the last 2 minutes"

• Brachial blood pressure

  Beat-to-beat BP will be recorded continuously using finger plethysmography and calibrated to reflect both brachial artery systolic and diastolic blood pressure

  "Baseline/pre-LBNP", "During each LBNP stage (-20 mmHg, -30 mmHg, -40 mmHg, -50 mmHg) in the last 2 minutes"

Study Arms (4)

Young male adults

ACTIVE COMPARATOR

All young males will complete both conditions under study: 1) LBNP and LBNP + isometric handgrip exercise

Other: LBNP; Other: LBNP + Isometric handgrip exercise

Young females

ACTIVE COMPARATOR

All young females will complete both conditions under study: 1) LBNP and LBNP + isometric handgrip exercise

Other: LBNP; Other: LBNP + Isometric handgrip exercise

Older male adults

ACTIVE COMPARATOR

All older males will complete both conditions under study: 1) LBNP and LBNP + isometric handgrip exercise

Other: LBNP; Other: LBNP + Isometric handgrip exercise

Older female adults

ACTIVE COMPARATOR

All older females will complete both conditions under study: 1) LBNP and LBNP + isometric handgrip exercise

Other: LBNP; Other: LBNP + Isometric handgrip exercise

Interventions

LBNP OTHER

Participants will be exposed to a lower body negative pressure chamber protocol consisting of 5-min stages in the order of 20, -30, -40 and -50 mmHg.

Older female adults; Older male adults; Young females; Young male adults

LBNP + Isometric handgrip exercise OTHER

Participants will undergo 5-minute stages of LBNP at -20, -30, -40, and -50 mmHg in sequence. During the -30, -40, and -50 mmHg stages, they will perform a 2-minute isometric handgrip exercise, starting at the third minute and sustaining it for the remaining duration.

Older female adults; Older male adults; Young females; Young male adults

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• People aged 18-35 years or aged ≥ 65 years
• Healthy without symptons of orthostatic intolerance (i.e., nausea, sweating, weakness, visual disturbance)
• Seated systolic and/or diastolic BP \<140/90 mmHg;
• Body mass index \<35 kg/m2
• Recreationally active (≤ 2 days of structured physical activity)
• Regular menstrual cycles in young females

You may not qualify if:

• People diagnosed with cardiovascular, diabetes, inflammatory or renal diseases and neurodegenerative-related dementia
• Tobacco users
• People prescribed with beta-blockers
• Pregnant females
• People unable to fit or get into the lower body negative pressure chamber

Sponsors & Collaborators

• Tracy Baynard: lead

Study Sites (1)

University of Massachusetts Boston

Boston, Massachusetts, 02125, United States

RECRUITING

Related Publications (7)

• Stock JM, Shenouda N, Chouramanis NV, Patik JC, Martens CR, Farquhar WB, Chirinos JA, Edwards DG. Effect of acute handgrip and aerobic exercise on wasted pressure effort and arterial wave reflections in healthy aging. Am J Physiol Heart Circ Physiol. 2023 Oct 1;325(4):H617-H628. doi: 10.1152/ajpheart.00133.2023. Epub 2023 Jul 21.

  PMID: 37477688 BACKGROUND

• Stratton JR, Halter JB, Hallstrom AP, Caldwell JH, Ritchie JL. Comparative plasma catecholamine and hemodynamic responses to handgrip, cold pressor and supine bicycle exercise testing in normal subjects. J Am Coll Cardiol. 1983 Jul;2(1):93-104. doi: 10.1016/s0735-1097(83)80381-7.

  PMID: 6853921 BACKGROUND

• Goswami N, Blaber AP, Hinghofer-Szalkay H, Convertino VA. Lower Body Negative Pressure: Physiological Effects, Applications, and Implementation. Physiol Rev. 2019 Jan 1;99(1):807-851. doi: 10.1152/physrev.00006.2018.

  PMID: 30540225 BACKGROUND

• Ricci F, Fedorowski A, Radico F, Romanello M, Tatasciore A, Di Nicola M, Zimarino M, De Caterina R. Cardiovascular morbidity and mortality related to orthostatic hypotension: a meta-analysis of prospective observational studies. Eur Heart J. 2015 Jul 1;36(25):1609-17. doi: 10.1093/eurheartj/ehv093. Epub 2015 Apr 6.

  PMID: 25852216 BACKGROUND

• Fu Q, Arbab-Zadeh A, Perhonen MA, Zhang R, Zuckerman JH, Levine BD. Hemodynamics of orthostatic intolerance: implications for gender differences. Am J Physiol Heart Circ Physiol. 2004 Jan;286(1):H449-57. doi: 10.1152/ajpheart.00735.2002. Epub 2003 Oct 2.

  PMID: 14527942 BACKGROUND

• Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, van Dijk JG. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011 Apr;21(2):69-72. doi: 10.1007/s10286-011-0119-5. No abstract available.

  PMID: 21431947 BACKGROUND

• Fedorowski A, Ricci F, Hamrefors V, Sandau KE, Hwan Chung T, Muldowney JAS, Gopinathannair R, Olshansky B. Orthostatic Hypotension: Management of a Complex, But Common, Medical Problem. Circ Arrhythm Electrophysiol. 2022 Mar;15(3):e010573. doi: 10.1161/CIRCEP.121.010573. Epub 2022 Feb 25.

  PMID: 35212554 RESULT

MeSH Terms

Conditions

Orthostatic Intolerance

Interventions

Lower Body Negative Pressure

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Decompression; Therapeutics

Central Study Contacts

João L. Marôco, MS

CONTACT

7738933897; joao.maroco001@umb.edu

Tracy Baynard, PhD

CONTACT

12178404493; tracy.baynard@umb.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor/Associate Vice Provost for Graduate Education

Study Record Dates

• First Submitted: March 28, 2025
• First Posted: April 22, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.

Locations

US (1)