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

Abstract

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 O₂ 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 ( r² = 0.97) and CVCi-PetCO₂ ( r² = 0.93) was superior to linear regression ( r² = 0.91, r² = 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.