Steady-state cardiovascular responses during head-up tilt in Veterans with Gulf War Illness

Gulf War Illness (GWI) is a chronic, multi-symptom condition characterized by fatigue, cognitive difficulties, pain, and autonomic dysfunction. Veterans with GWI (GWI+) frequently report orthostatic intolerance and symptoms consistent with impaired autonomic and cerebrovascular regulation. Because head-up tilt challenges autonomic control, it provides a physiological assessment to reveal potential impairments. Thus, the objective of this study was to determine whether GWI+ exhibit altered middle cerebral artery velocity (MCAv), blood pressure (BP), and heart rate (HR) responses during graded head-up tilt (HUT) compared with Veterans without GWI (GWI-). We hypothesized that GWI+ group would show greater MCAv reductions and exaggerated HR responses during HUT tests. A total of thirty-nine Veterans participated in the study (GWI-: n=16 and GWI+: n=23). During the laboratory visit, continuous MCAv by transcranial Doppler, mean arterial pressure (MAP) by finger photoplethysmography, and HR by 3-lead electrocardiogram were recorded during supine, 30° HUT, and 60° HUT. Steady-state responses were defined at minute 2-3 of each tilt stage. Percent changes from baseline (%MCAv, %MAP, %HR) were compared between GWI- and GWI+ using ANOVA. The groups were not different in age (60 ± 4 vs. 59 ± 4 yrs; p = 0.324). There were no group differences between GWI- and GWI+ in resting MAP (99 ± 9 vs. 101 ± 10 mmHg, p = 0.398) and resting HR (64 ± 15 vs. 63 ± 10 bpm, p = 0.830). As expected, HUT resulted in significant decreases in steady-state MCAv, and increases in HR in both groups (p < 0.05). There were no significant changes in MAP with HUT. MCAv significantly decreased with HUT in both groups, with a decrease from 30° HUT to 60° HUT in both GWI- and GWI+ Veterans (GWI-: -3.5% to -12.0% and GWI+: -6.6% to -10.1%, both p < 0.05). However, there were no group differences in the change in MCAv at either 30° HUT (GWI-: -3.5% vs. GWI+: -6.6%, p > 0.05) or 60° HUT (GWI-: -12.0% vs. GWI+: -10.1%, p > 0.05), suggesting similar tilt-induced reductions in cerebral blood velocity. There were no group differences in the change in MAP at either 30° HUT (GWI-: -3.5% vs. GWI+: -4.0%) or 60° HUT (GWI-: -3.1% vs. GWI+: -1.8%, p > 0.05). There was a significant group and angle interaction for HR (p < 0.05). HR increased significantly from 30° HUT to 60° HUT in both groups (GWI-: 4.5% to 16.2% and GWI+: 6.0% to 25.2%, both p < 0.05). At 30° HUT, there were no group differences in the magnitude of change in HR (GWI+: 6.0% vs. GWI-: 4.5%, p = 0.69), but at 60° HUT, the change in HR was significantly greater in GWI+ than in GWI- (GWI+: 25.2% vs. GWI-: 16.2%, p < 0.05) Veterans. This HR response in GWI+ reflects heightened cardiac activation despite similar reductions in MCAv. In conclusion, these findings indicate that GWI+ Veterans have enhanced HR responses during orthostatic stress when compared with GWI- Veterans, despite similar MCAv reductions. These findings suggest that autonomic dysfunction rather than impaired cerebral perfusion during HUT in GWI+ Veterans may underlie orthostatic symptoms in GWI. Supported by the Department of Defense: W81XWH1910381 and NIH T32HL007936 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.