Hypocapnia and cerebral hypoperfusion in orthostatic intolerance

Background and Purpose - Orthostatic and other stresses trigger tachycardia associated with symptoms of tremulousness, shortness of breath, dizziness, blurred vision, and, often, syncope. It has been suggested that paradoxical cerebral vasoconstriction during head-up tilt might be present in patients with orthostatic intolerance. We chose to study middle cerebral artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation during tilt in patients with orthostatic intolerance (OI). Methods - Beat-to-beat BFV from the MCA, heart rate, CO₂, blood pressure (BP), and respiration were measured in 30 patients with OI (25 women and 5 men; age range, 21 to 44 years; mean age, 31.3±1.2 years) and 17 control subjects (13 women and 4 men; age range, 20 to 41 years; mean age, 30±1.6 years); ages were not statistically different. These indices were monitored during supine rest and head-up tilt (HUT). We compared spontaneous breathing and hyperventilation and evaluated the effect of CO₂ rebreathing in these 2 positions. Results - The OI group had higher supine heart rates (P < 0.001) and cardiac outputs (P < 0.01) than the control group. In response to HUT, OI patients underwent a greater heart rate increment (P < 0.001) and greater reductions in pulse pressure (P < 0.01) and CO₂ (P < 0.001), but total systemic resistance failed to show an increment. Among the cerebrovascular indices, all BFVs (systolic, diastolic, and mean) decreased significantly more, and cerebrovascular resistance (CVR) was increased in OI patients (P < 0.01) compared with control subjects. In both groups, hyperventilation induced mild tachycardia (P < 0.001), a significant reduction of BFV, and a significant increase of CVR associated with a fall in CO₂. Hyperventilation during HUT reproduced hypocapnia, BFV reduction, and tachycardia and worsened symptoms of OI; these symptoms and indices were improved within 2 minutes of CO₂ rebreathing. The relationships between CO₂ and BFV and heart rate were well described by linear regressions, and the slope was not different between control subjects and patients with OI. Conclusions - Cerebral vasoconstriction occurs in OI during orthostasis, which is primarily due to hyperventilation, causing significant hypocapnia. Hypocapnia and symptoms of orthostatic hypertension are reversible by CO₂ rebreathing.