Associate Professor of Medicine University of Toronto Toronto, Ontario, Canada
Background: The clinical assessment of orthostatic intolerance (OI) involves monitoring heart rate (HR) and blood pressure (BP) during supine rest followed by 10 minutes of unsupported standing. Diagnostic criteria depend on the magnitude and timing of HR and BP changes; however, these responses offer limited insight into underlying mechanisms, including preload, cardiac output (CO), and vasoconstriction. Improved understanding of normal hemodynamic responses to standing, and the effects of age, may enhance our understanding of vulnerability of specific populations to OI.
METHODS AND RESULTS: We conducted a study examining hemodynamic effects of a 10-minute active stand in younger and older self-reported healthy adults. At supine rest and at 1, 3, 5, and 10 minutes of standing, HR and BP were measured non-invasively. Additional assessments included ventilation (VE), oxygen uptake (VO2), near-infrared spectroscopy of the vastus lateralis to evaluate skeletal muscle oxygenation (SmO2) and total hemoglobin (THb) as markers of peripheral pooling. A subset of participants also underwent invasive hemodynamic monitoring. To date, 39 subjects have been recruited: younger (n=16; age=28 ± 7y; M:F=8:8) and older (n=23; age=62 ± 8y; M:F=5:18). Older adults demonstrated a limited HR increase throughout standing (p < 0.027) despite similar supine HR. Supine mean arterial pressure (MAP) was higher in older adults (p < 0.001), but MAP declined more significantly during standing (p < 0.001). SmO2 was consistently lower in older adults (p < 0.024), while THb increased more at 3, 5, and 10 minutes (p < 0.036), suggesting greater venous pooling. VE and VO2 were reduced in older adults across all time points (p < 0.039). 18 subjects completed the invasive protocol (age=48 ± 18y; M:F=10:8), which included pressure-time waveforms from the right atrium, right ventricle, pulmonary artery, and pulmonary capillary wedge position. Mixed-venous oxygen saturation (SvO2) and VO2 enabled direct Fick calculation of CO, stroke volume (SV), and vascular resistance (SVR). SV and CO declined by 0.7–0.8-fold, despite a 1.2-fold increase in HR. MAP was maintained with a 1.3-fold increase in SVR.
Conclusion: Orthostasis is a complex stress to cardiovascular physiology. We observed declines in SV and intracardiac filling pressures, indicating reduced preload. HR may increase to compensate for reduced SV, although CO remains decreased. Older adults exhibit a limited chronotropic response and a reduced ability to maintain MAP during orthostasis. Despite a lower VO2 during standing, older adults show increased oxygen extraction and greater peripheral pooling, indicative of a limited skeletal muscle pump. These findings highlight age-related hemodynamic responses that may contribute to OI susceptibility.
