Decreased upright cerebral blood flow and cerebral autoregulation in normocapnic postural tachycardia syndrome

Abstract

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

Fig. 1.

Percent change in cerebral blood flow velocity (CBFV) during tilt. Postural tachycardia syndrome (POTS) subjects, during tilt, exhibited an ∼20% decrease in CBFV, whereas controls exhibited an ∼10% decrease. *P < 0.05 compared with controls.

Fig. 2.

Static autoregulation in a representative POTS subject and a control subject during tilt. A: mean arterial pressure (MAP) oscillations during tilt. B: CBFV oscillations during tilt. Arrows represent the beginning and end of tilt (range: 600 s). In POTS subjects, CBFV initially fell upon tilt and did not recover until the return to the supine position. In control subjects, CBFV initially fell but soon recovered and remained relatively stable throughout the duration of the tilt.

Fig. 3.

Dynamic autoregulation in a representative POTS subject and a control subject in the supine position and during tilt. A: 1-min interval of a POTS subject's AP and CBFV while in the supine position. B: 1-min interval of a POTS subject's AP and CBFV during tilt. C: 1-min interval of a control subject's AP and CBFV while in the supine position. D: 1-min interval of a control subject's AP and CBFV during tilt. In the supine position, there did not appear to be a strong relationship between AP and CBFV in either POTS or control subjects. In POTS subjects during tilt, AP and CBFV became very synchronous, oscillations in CBFV passively followed oscillations in AP, and dynamic autoregulation was reduced. In control subjects during tilt, AP and CBFV were less synchronous, demonstrating intact dynamic autoregulation.

Fig. 4.

Frequency domain transfer function of MAP and CBFV for a representative POTS subject supine (A) and upright (B) and control subject supine (C) and upright (D). During tilt, there was an increase in low frequency (LF; 0.04–0.15 Hz) coherence between MAP and CBFV in both POTS and control subjects and an increase in high frequency (HF; 0.15–0.40 Hz) coherence between MAP and CBFV in POTS subjects. During tilt, POTS patients had a significant increase in LF gain. In POTS subjects during tilt, phase tended to decrease and approached zero as frequency increased into the HF range.

Fig. 5.

LF (0.04–0.15 Hz) coherence between MAP and CBFV in POTS and control subjects in the supine position and during tilt. Both POTS and control subjects exhibited an increase in LF coherence during tilt. *P < 0.05 compared with supine measurements.