Comparisons of the Nonlinear Relationship of Cerebral Blood Flow Response and Cerebral Vasomotor Reactivity to Carbon Dioxide under Hyperventilation between Postural Orthostatic Tachycardia Syndrome Patients and Healthy Subjects

Abstract

Postural orthostatic tachycardia syndrome (POTS) typically occurs in youths, and early accurate POTS diagnosis is challenging. A recent hypothesis suggests that upright cognitive impairment in POTS occurs because reduced cerebral blood flow velocity (CBFV) and cerebrovascular response to carbon dioxide (CO2) are nonlinear during transient changes in end-tidal CO2 (PETCO2). This novel study aimed to reveal the interaction between cerebral autoregulation and ventilatory control in POTS patients by using tilt table and hyperventilation to alter the CO2 tension between 10 and 30 mmHg. The cerebral blood flow velocity (CBFV), partial pressure of end-tidal carbon dioxide (PETCO2), and other cardiopulmonary signals were recorded for POTS patients and two healthy groups including those aged >45 years (Healthy-Elder) and aged <45 years (Healthy-Youth) throughout the experiment. Two nonlinear regression functions, Models I and II, were applied to evaluate their CBFV-PETCO2 relationship and cerebral vasomotor reactivity (CVMR). Among the estimated parameters, the curve-fitting Model I for CBFV and CVMR responses to CO2 for POTS patients demonstrated an observable dissimilarity in CBFVmax (p = 0.011), mid-PETCO2 (p = 0.013), and PETCO2 range (p = 0.023) compared with those of Healthy-Youth and in CBFVmax (p = 0.015) and CVMRmax compared with those of Healthy-Elder. With curve-fitting Model II for POTS patients, the fit parameters of curvilinear (p = 0.036) and PETCO2 level (p = 0.033) displayed significant difference in comparison with Healthy-Youth parameters; range of change (p = 0.042), PETCO2 level, and CBFVmax also displayed a significant difference in comparison with Healthy-Elder parameters. The results of this study contribute toward developing an early accurate diagnosis of impaired CBFV responses to CO2 for POTS patients.

Effect of lower body negative pressure on cardiac and cerebral function in postural orthostatic tachycardia syndrome: A pilot MRI assessment

“…The current hypothesis is that the cerebral symptoms experienced by patients with POTS are associated with altered cerebrovascular responsiveness. Indeed, studies using oximetry to measure cerebral tissue saturation in response to orthostatic challenge have suggested an altered response in patients with POTS (Kharraziha et al., 2019; Tanaka et al., 2002), but no study to date has demonstrated differences in the response to tilt between patients with POTS and controls using transcranial Doppler ultrasound (Esch et al., 2010; Lin et al., 2020). In this regard, our findings align with, and extend, the previous research.…”

“…Previous studies measuring resting cerebral blood velocity using transcranial Doppler ultrasound report no difference in patients with POTS compared to healthy adults (Lin et al, 2020;Ocon et al, 2012;Stewart et al, 2015;Stewart & Medow, 1985;Wells et al, 2020). However, the limitations of transcranial Doppler include the inability to measure volumetric flow or provide information about cerebral oxygen consumption (Willie et al, 2011).…”

“…Indeed, cerebral tissue saturation measured by oximetry was previously reported to be lower in patients with POTS upon standing (Kharraziha et al., 2019). However, studies using transcranial Doppler ultrasound to measure cerebral blood velocity have yet to demonstrate differences at rest or in response to orthostatic challenge between the two groups (Gelpi et al., 2023; Lin et al., 2020; Stewart et al., 2015; Stewart & Medow, 1985; Wells et al., 2020). To date, measures of cerebrovascular function using magnetic resonance imaging (MRI) have not been performed in this population and may provide additional mechanistic insight due to the ability to measure CBF, regional perfusion, and oxygen uptake (e.g., cerebral VO 2 ).…”

“…Indeed, cerebral tissue saturation measured by oximetry was previously reported to be lower in patients with POTS upon standing (Kharraziha et al, 2019). However, studies using transcranial Doppler ultrasound to measure cerebral blood velocity have yet to demonstrate differences at rest or in response to orthostatic challenge between the two groups (Gelpi et al, 2023;Lin et al, 2020;Stewart et al, 2015;Stewart & Medow, 1985;Wells et al, 2020).…”