Transcranial Doppler estimation of cerebral blood flow and cerebrovascular conductance during modified rebreathing

Clinical transcranial Doppler assessment of cerebral vasomotor reactivity (CVMR) uses linear regression of cerebral blood flow velocity (CBFV) vs. end-tidal CO2 ( PETCO2) under steady-state conditions. However, the cerebral blood flow (CBF)-PETCO2 relationship is nonlinear, even for moderate changes in CO2. Moreover, CBF is increased by increases in arterial blood pressure (ABP) during hypercapnia. We used a modified rebreathing protocol to estimate CVMR during transient breath-by-breath changes in CBFV and PETCO2. Ten healthy subjects (6 men) performed 15 s of hyperventilation followed by 5 min of rebreathing, with supplemental O-2 to maintain arterial oxygen saturation constant. To minimize effects of changes in ABP on CVMR estimation, cerebrovascular conductance index (CVCi) was calculated. CBFV-PETCO2 and CVCi-PETCO2 relationships were quantified by both linear and nonlinear logistic regression. In three subjects, muscle sympathetic nerve activity was recorded. From hyperventilation to rebreathing, robust changes occurred in PETCO2 (20-61 Torr), CBFV (-44 to +104% of baseline), CVCi (-39 to +64%), and ABP (-19 to +23%) (all P < 0.01). Muscle sympathetic nerve activity increased by 446% during hypercapnia. The linear regression slope of CVCi vs. PETCO2 was less steep than that of CBFV (3 vs. 5%/Torr; P = 0.01). Logistic regression of CBF-PETCO2 (r(2) = 0.97) and CVCi-PETCO2 (r(2) = 0.93) was superior to linear regression (r(2) = 0.91, r(2) = 0.85; P = 0.01). CVMR was maximal (6-8%/Torr) for PETCO2 of 40-50 Torr. In conclusion, CBFV and CVCi responses to transient changes in PETCO2 can be described by a nonlinear logistic function, indicating that CVMR estimation varies within the range from hypocapnia to hypercapnia. Furthermore, quantification of the CVCi-PETCO2 relationship may minimize the effects of changes in ABP on the estimation of CVMR. The method developed provides insight into CVMR under transient breath-by-breath changes in CO2.