Altered profile of baroreflex and autonomic responses to lower body negative pressure in chronic orthostatic intolerance

Background: Chronic orthostatic intolerance (COI) is a common and disabling autonomic syndrome of unclear pathophysiology. We tested the hypothesis that baroreflex and autonomic responses to graded lower body suction (LBNP, up to -40 mmHg) could be altered in COI patients. Methods: Electrocardiogram (ECG), non-invasive arterial blood pressure and respiratory activity were measured during progressive LBNP (seven patients and seven volunteers). Lumped arterial baroreflex sensitivity (a index), and its arterial and cardiopulmonary components, were assessed by multivariate closed-loop analysis of RR interval and systolic arterial pressure (SAP) spontaneous variabilities and respiration. Monovariate spectral analysis of RR interval and SAP variability provided markers of autonomic regulation of the sinoatrial (SA) node and of vascular sympathetic modulation. Results: Similar reductions in overall and cardiopulmonary baroreflex gain were observed in both groups in response to graded LBNP. In contrast, only controls demonstrated a selective increase in arterial baroreflex sensitivity, at low-grade LBNP. Clear increases in the low-frequency component of RR interval variability (LF_RR) [and decreases in the high-frequency component of RR interval variability (HF _RR), both in normalized units] were observed in controls with graded LBNP, while insignificant changes occurred in COI patients, who showed, conversely, exaggerated sympathetic vasomotor responses [as assessed by the low frequency component of SAP variability (LF_SAP)]. Conclusions: Patients with chronic orthostatic intolerance show distinct signs of altered baroreflex and autonomic regulation of the SA node and of the vasculature in response to graded LBNP.