Abstract 033: Novel Neurohumoral Responses to Head Upright Tilt Testing in Children with Chronic Nausea and Orthostatic Intolerance

Abstract

Children with chronic unexplained nausea have a high incidence of orthostatic intolerance (OI), with exaggerated suppression of baroreflexes upon standing. The renin-angiotensin system (RAS) is known to play a role in disorders related to OI likely as a compensatory mechanism for CV regulation. The objective of this study was to characterize the neurohumoral response to head upright tilt testing (HUT) in children with chronic nausea and OI. Forty-eight patients (mean age [range] of 15 [10-18] years)(36 females, 12 males) completed HUT. GI symptoms including nausea were reported during HUT. Subjects were maintained supine for 15 min before 45 min 70° HUT. Plasma hormones catecholamines (Cat), epinephrine (Epi), norepinephrine (NE), vasopressin (AVP), aldosterone (Aldo), renin, and angiotensins [Ang-(1-7) and AngII] were measured in blood sampled immediately before and after 15 min of upright tilt. Of the 48 HUTs, 35 subjects demonstrated OI. There were no differences in supine blood pressures (BP) or humoral measures between groups. OI subjects had lower systolic (105 ± 4 vs. 127 ± 4 mm Hg, p=0.001), diastolic (61 ± 2 vs. 77 ± 2, p<0.0001), and mean arterial (76 ± 2 vs. 93 ± 2, p=0.0002) BPs during HUT compared to normal subjects (mean ± SEM). They also had higher Cat (625 ±44 vs. 466 ± 61 pg/ml, p=0.02), AngII (48 ± 3 vs. 35 ± 4 pg/ml, p=0.04), and AVP (46 ± 12 vs. 18 ± 14 pg/ml, p=0.01) during HUT compared to non-OI subjects. There was a negative correlation between Ang-(1-7) and NE at baseline (r=-0.6, p<0.05) and HUT (r=-0.6, p=0.03) in Non-OI subjects that was not seen in OI subjects. Nausea was reproduced by HUT in 42% (20 of 48) of this cohort. Nausea subjects did not have a change in DBP (61 ± 2 vs. 61 ± 3 mm Hg) upon tilt, but had significantly higher AVP (72 ± 20 pg/ml, p=0.01) during HUT compared to subjects who did not experience nausea (15 ± 7, p=0.001). Children with chronic nausea testing positive for OI have elevated Cat, AngII, and AVP levels upon HUT. Elevated serum AVP may be a key trigger to nausea with orthostatic challenge independent of OI on HUT. In addition to this humoral response, the absence of change in DBP upon standing suggests a failure in both the sympathetic nervous system and RAS compensatory mechanisms necessary to sustain HUT in children with chronic nausea and OI.