Decreased Upright Cerebral Blood Flow and Cerebral Autoregulation in POTS
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.
Beat-to-beat BP was monitored using finger arterial plethysmography (Finometer, FMS, Amsterdam, The Netherlands) of the right middle or index fingers. These data were calibrated to brachial AP. The Finometer contains a sensor that corrects for height during positional changes, such as tilting. A single-lead ECG measured HR. A nasal cannula connected to a capnograph with a pulse oximeter (Smiths Medical, Waukesha, WI) measured ETCO2. Respirations were measured using a RespiTrace device (NIMS, North Bay Village, FL). Transcranial Doppler (Neurovision, Multigon, Yonkers, NY) measured cerebral blood flow velocity (CBFV) of the left middle cerebral artery (MCA) using a 2-MHz probe fixed to the subjectís head by a custom-made headband.
After instrumentation, subjects remained in the supine position for 30 min to acclimate. After acclimation, at least 5 min of continuous baseline data were recorded. With the completion of supine measurements, the 70į HUT test began. The tilt test continued for a maximum of 10 min. All subjects in both the POTS and control groups finished the full 10-min tilt test without any adverse events.
BP and CBFV variability and transfer function. The variation between BP and CBFV was measured using conventional transfer analysis as used for HR and BP variability and transfer function. CBFV variability was defined as the variation in the measured CBFV as seen in the frequency domain. MAP and CBFV were analyzed, and the transfer function was calculated. Minimum BP-CBFV coherence values of 0.5 were fulfilled for each subject and prevented the inclusion of excessively noisy signals. Coherence, gain, and phase as a function of frequency were applied to describe dynamic CA in the frequency domain. Coherence describes the correlation between oscillations in MAP and CBFV in the frequency domain. It is the Fourier transform of the cross covariance. A low degree of coherence implies strong autoregulation with because, while BP may change, blood flow remains constant. Conversely, an increase in coherence implies weak autoregulation with a maximum of coherence of 1.0, signifying perfect synchrony between BP and CBF (54). Gain, or magnitude, describes the ratio between the oscillatory amplitudes of MAP and CBFV (54). Phase represents the time lag measured in fractions of an oscillation of MAP and CBFV, with oscillations in CBFV normally preceding changes in MAP (54). An increase in phase is expected upon standing and indicates that MAP and CBF may be falling out of synchrony. Note that such analyses depend critically on the linear and statistically stationary properties of the quantities measured in two quasi-steady states. Thus the heart rate, BP, and CBF are relatively steady when supine and also when upright although the nature of stationarity may vary between the two states (supine and upright).
This study demonstrates new findings about CA in both POTS and healthy control subjects. First, we showed that in young, normocapnic POTS subjects, CBFV drops by 19.5% compared with only 10.3% in healthy controls during HUT. In POTS subjects, this could not be accounted for by a posturally induced change in ETCO2 alone because that would only accounted for a 12% decrease. Static autoregulation (i.e., the average change in CBFV at a given AP) was, therefore, decreased in POTS subjects compared with control subjects and remained decreased throughout the tilt.Second, although transfer function analysis of BP and CBFV implicitly involve the computation of CBFV variability, we are, to our knowledge, first to make explicit use of CBFV variability measurements in relation to POTS. These are potentially important because they convey a tangible sense of how much and how rapidly CBF changes. CBFV variability, at LF, represents the overall effects of cerebrovascular transduction of BP, represented as Mayer waves , which appear with increased amplitude during tilt in POTS subjects. Mayer waves represent the increase in sympathetic baroreflex activity engendered by orthostasis (31, 35), and this increase in baroreflex activity is increased in POTS (Table 3). We additionally demonstrated that during HUT, only POTS subjects show an increase in the LF component of CBFV variability, whereas both POTS and control subjects show a smaller increase in the HF component. Similarly, the LF gain (transfer function amplitude) and CBF-index of MAP-CBFV variability increased during HUT only in POTS subjects. We demonstrated that the LF and HF coherence between MAP and CBFV increases during HUT in both POTS and control subjects but increased to a greater degree in POTS subjects. Also, the LF coherence between MAP and CBFV during HUT correlated with SBP, DBP, and MAP only in POTS subjects. The combination of increased Mayer wave amplitudes, increased gain, and increased coherence at LF accounts for the increase in CBFV variability. Corresponding observations were made in the time domain , in which oscillations in AP were nearly synchronous with oscillations in CBFV. Also, we demonstrated how static and dynamic CA are ineffective in maintaining CBFV during tilt.
Implications for POTS Patients
Dynamic and static autoregulation are less effective in young, normocapnic POTS subjects compared with control subjects during HUT, as demonstrated by the decreased CBFV, increased LF (0.1 Hz) and HF (0.25 Hz) coherence between MAP and CBFV, and increased LF gain, with a lack of an associated change in phase differences, which remained low. This results in a lower CBFV with greater CBFV variability at LF, i.e., greater oscillations in the already reduced CBF, which are signs of both static and dynamic autoregulatory deficits. The frequency of 0.1 Hz converts to a time scale of 10 s, and half of an oscillatory period would be 5 s. This means that CBF is further decreased for 5 s and increased for 5 s compared with the reduced static baseline. As a result, substantially lowered CBF occurs 50% of the time in POTS subjects compared with control subjects when upright, which can impair cerebral perfusion and neurocognitive function. A decrease in perfusion of the brain may help to explain the symptoms of lightheadedness, dizziness, and mental confusion that are common in POTS patients . Dynamically, oscillations in CFBV coincide with oscillations in AP . Since POTS subjects exhibited lower MAP than controls, therapies that increase MAP may also increase CBFV, possibly alleviating the cognitive impairment.
Recent findings seem to indicate that all POTS patients have defects in cerebral autoregulation which can be static, involving a >25% reduction in cerebral blood flow, or dynamic with close coupling between blood pressyre and cerebral blood flow over the critical 0.05-0.5 Hz frequency range. Moreover static autoregulatory dysfunction results in hyperpnea, hypocapnia and sympathetic activation which may be the cause of a hyperadrenergic POTS variant in these patients. This may be amenable to individualized treatment.