Tumor Necrosis Factor-alpha Adversely Influences Myocardial Oxygen Demand and Exercise Tolerance in Postmenopausal Women

Abstract

Oxidative stress-mediated arterial stiffening is related to the pathophysiological progression of vascular dysfunction with advancing age. However, the functional implications concerning the involvement of tumor necrosis factor-alpha (TNF-α), a marker of oxidative stress, on hemodynamic responses at rest and during physical exertion are unclear. PURPOSE: The aims of this investigation were to examine the independent effects of TNF-α on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the influence of TNF-α on exercise tolerance. METHODS: Forty, postmenopausal (65 ± 3 years) women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake. Local pulse contour analyses were used to assess large artery compliance while rate-pressure product (RPP), a reliable index of myocardial oxygen demand, was measured at rest and during two submaximal workloads. RPP was calculated by dividing the product of heart rate and systolic blood pressure (via auscultation) by 100. Exercise tolerance corresponded with the cessation of the graded exercise test. P-values ≤ 0.05 were considered statistically significant for all analyses. RESULTS: Multiple linear regression revealed a positive association between TNF-α and RPP during submaximal exercise (partial r = 0.43; p = 0.015) adjusted for maximal heart rate, maximal oxygen uptake, large artery compliance, and percent body fat. Path analyses revealed a significant indirect effect of large artery compliance on exercise tolerance through TNF-α, β = 0.13, CI [0.03, 0.35] such that heightened levels of TNF-α translated to poorer exercise tolerance. CONCLUSIONS: These data indicate that TNF-α is independently associated with myocardial oxygen demand during submaximal exercise equating to 5 METs but not at rest and TNF-α mediates the indirect effects of large artery compliance on exercise tolerance. Future studies should explore differential responses to standardized exercise tasks among older adults and consider the influence of exercise training on myocardial oxygen demand and activity-related energy expenditure.