Author ORCID Identifier

0000-0002-5691-5272

Date of Award

8-31-2026

Document Type

Campus Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Exercise and Health Science

First Advisor

Dr. Bo Fernhall

Abstract

Low orthostatic tolerance is more prevalent in females. However, it is unclear whether advancing age exacerbates this sex difference or the mechanisms underlying low-upright tolerance. This dissertation tested whether lower-body negative pressure (LBNP)-induced cardiac unloading increases left-ventricular work without favoring ejection (wasted pressure effort, WPE) and promotes ventricular-arterial mismatch less in younger females than in males, with responses potentially exacerbated in older females. It also examined the effects of isometric handgrip (IHG), a feasible strategy for orthostatic intolerance, on ventricular-arterial interactions. Twenty-seven females (17 younger, 10 older) and eighteen younger males completed two visits: LBNP (4x5-min stages: −10 to −50 mmHg) and LBNP+IHG (last 3 stages). Cardiac volumes and flow were measured by echocardiography, and carotid end-systolic pressure (ESP) by tonometry. Ventricular–arterial coupling was expressed as the ratio of arterial elastance (ESP/stroke volume) to ventricular elastance (ESP/end-systolic volume; Ea/Ees). Wasted pressure effort (WPE) was calculated as the systolic pressure–time integral minus flow multiplied by aortic characteristic impedance. Pre-syncope was noted in seven females (4 younger), indicating lower tolerance than males (Fisher’s p=0.045), with no age-related differences among females. IHG had a negligible effect on time to pre-syncope and LBNP tolerance in females (log-rank p=0.380). LBNP increased Ea more in younger females than in males (Δ50-rest [F-M]=1.52 mmHg/mL, p=0.003) without Ees changes, increasing Ea/Ees (p=0.043). WPE decreased similarly across sex (Δ50-pre= −1.13 mmHg·s, p< 0.001). Within females, older age was associated with higher Ees (p< 0.001) and a blunted LBNP-induced increase in Ea (Δ50-20 [Older-Younger]= −1.15 mmHg/mL, p=0.026), yielding a smaller Ea/Ees increase (Δ50-20 = −0.27, p=0.045). WPE increased only in older females during LBNP (Δ50-Pre= 0.72 mmHg·s, p=0.048). During LBNP+IHG, the sex difference in Ea was abolished (Δ50-rest [F-M]= 0.33 mmHg/mL, p=0.447), while females exhibited age-independent attenuation of the Ea increase (Δ50-Pre = −1.34 mmHg/mL, p=0.004), reducing the rise in Ea/Ees irrespective of sex or age. Ees increased in both sexes (Δ50-rest [HG-LBNP]=0.96 mmHg/mL, p< 0.001), whereas older females exhibited reductions at peak LBNP+HG (age-by-time-by-condition, p=0.048). IHG did not alter WPE in any group (p>0.05). Findings suggest age- and sex-specific ventricular-arterial responses to cardiac unloading without contributing to orthostatic tolerance.

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