Predicting orthostatic intolerance: physics or physiology?

To adequately assess the viability of any particular causal theory of orthostatic intolerance, physical and physiological parameters thought to be associated with orthostasis must be evaluated simultaneously within the same individual. Time, cost, and complexity of instrumentation generally limit studies of orthostatic intolerance to a single independent effect for any given sample of subjects. We, therefore, measured 6 key physical and physiological variables associated with various theories of orthostatic intolerance in 14 males to test the hypothesis that physical factors rather than physiological reflex mechanisms were dominant in contributing to orthostatic tolerance. Measurements included height, plasma volume (expressed as percent of total weight), variation in R-R interval, leg compliance, and carotid-cardiac (high pressure), and cardiopulmonary (low pressure) baroreflex sensitivity. Subjects' orthostatic intolerance was quantified by time to syncope during progressive supine lower body decompression. Correlations, regression coefficients, and indices of replicability were calculated using 500 to 1,000 bootstrap resamplings of the original 14 observations. Although all six measurements correlated with time to syncope when evaluated individually, only height (negative), percent plasma volume weight (positive), and, to a lesser extent, carotid-cardiac baroreflex sensitivity yielded consistent (reproducible) results when all measures were tested simultaneously. These results suggest that while orthostatic intolerance may be dependent upon a variety of physiological reflexes, physical factors such as height and plasma volume tend to dominate the prediction of time to syncope during lower body negative pressure (LBNP). Physiological reflexes, which act to maintain adequate profusion to the brain during normal terrestrial posture in humans, may be overwhelmed by the additional orthostatic challenge imposed by progressive lower body decompression.