Effects of Vestibular Loss on Orthostatic Mechanisms

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When standing upright, the maintenance of stable blood pressure is challenged by the lengthening of the orthostatic (hydrostatic) column. We hypothesize that the vestibular otolith organs provide short-latency orientation information that contributes to autonomic cardio-respiratory regulation during changes in posture. This hypothesis will be tested by first comparing non-invasive measurements of blood pressure and circulation during upright tilts from different orientations that provide the same orthostatic stress but different stimuli to the otoliths. We predict that due to varying stimuli to the otoliths, the early cardio- respiratory responses to upright tilt in healthy subjects will differ depending on the direction of tilt whereas responses during the later portions of upright tilt will be similar regardless of the direction of tilt due to activation of other cardio-respiratory (e.g., baroreflex) mechanisms. Second, we will assess the effects of vestibular loss on orthostatic mechanisms by comparing tilt data from subjects with known bilateral vestibular deficiency to corresponding data from healthy individuals matched for age and gender. We predict the early cardio-respiratory responses to upright tilt in patients with vestibular loss will be compromised regardless of the direction of tilt. Twelve subjects with bilateral loss of vestibular function and twelve healthy subjects will be tested during one session consisting of four 10 min tilts performed with eyes closed from a horizontal orientation to 80 deg upright (supine - pitch tilt, prone - pitch tilt, right ear down - roll tilt and left ear down - roll tilt). Modulation of arterial blood pressure, heart rate, stroke volume, peripheral vascular resistance, end-tidal C02, respiratory rate and volume, cerebral blood flow velocity and cerebrovascular resistance will be measured during the tilt stimuli. During a second set of experiments, the contribution of the otoliths to orthostatic responses will be assessed as subjects are continuously rotated about an earth horizontal axis at varying frequencies with head facing straight ahead or turned to the side. We predict that cardio- respiratory responses will be modulated as a function of head orientation relative to gravity and frequency in healthy subjects but not in subjects with bilateral vestibular deficiency. This study will provide new information on how vestibular loss might increase susceptibility for orthostatic intolerance, and will provide new insights on otolith- autonomic human subjects.