Decreased Upright Cerebral Blood Flow and Cerebral Autoregulation in Normocapnic 1 Postural Tachycardia Syndrome

22 The postural tachycardia syndrome (POTS), a chronic form of orthostatic intolerance, has 23 signs and symptoms of lightheadedness, loss of vision, headache, fatigue, and neurocognitive 24 deficits consistent with reductions in cerebrovascular perfusion. We hypothesized that young, 25 normocapnic POTS patients exhibit abnormal cerebral autoregulation (CA) that results in 26 decreased static and dynamic cerebral blood flow autoregulation. All subjects had continuous 27 recordings of mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV), using 28 transcranial Doppler sonography, both supine and during a 70° head-up tilt. During tilt, POTS 29 patients (n=9) demonstrated a higher heart rate than controls (n=7) (109 ± 6 vs. 80 ± 2 bpm, p < 30 0.05); whereas controls demonstrated a higher MAP than POTS (87 ± 2 vs. 77 ± 3 mmHg, p < 31 0.05). Also during tilt, mean CBFV decreased 19.5 ± 2.6 % in POTS vs. 10.3 ± 2.0% in controls 32 (p < 0.05). We then used transfer function analysis of MAP and CFBV in the frequency domain 33 to quantify these changes. The low frequency (LF, 0.04-0.15 Hz) component of CBFV 34 variability increased during tilt in POTS (supine: 3 ± 0.9 vs. tilt: 9 ± 2, p < 0.02). In POTS 35 patients, there was an increase in LF and high frequency coherence between MAP and CBFV, an 36 increase in LF gain, and a lack of significant change in phase. Static CA may be less effective in 37 POTS compared to controls since immediately following tilt, CBFV decreased more in POTS, 38 was highly oscillatory, and autoregulation did not restore CBFV to baseline values until the 39 subjects became supine. Dynamic CA may be less effective in POTS because MAP and CBFV 40 during tilt became almost perfectly synchronous. We conclude that dynamic and static 41 autoregulation of cerebral blood flow are less effective in POTS patients compared with control 42 subjects during orthostatic challenge. 43 44