Comparison of Cerebral Vascular Reactivity Measures Obtained Using Breath-Holding and CO ₂ Inhalation

Stimulation of cerebral vasculature using hypercapnia has been widely used to study cerebral vascular reactivity (CVR), which can be expressed as the quantitative change in cerebral blood flow (CBF) per mm Hg change in end-tidal partial pressure of CO 2 (P ET CO 2 ). We investigate whether different respiratory manipulations, with arterial spin labeling used to measure CBF, lead to consistent measures of CVR. The approaches included: (1) an automated system delivering variable concentrations of inspired CO 2 for prospective targeting of P ET CO 2 , (2) administration of a fixed concentration of CO 2 leading to subject-dependent changes in P ET CO 2 , (3) a breath-hold (BH) paradigm with physiologic modeling of CO 2 accumulation, and (4) a maneuver combining breath-hold and hyperventilation. When CVR was expressed as the percent change in CBF per mm Hg change in P ET CO 2 , methods 1 to 3 gave consistent results. The CVR values using method 4 were significantly lower. When CVR was expressed in terms of the absolute change in CBF (mL/100g per minute per mm Hg), greater discrepancies became apparent: methods 2 and 3 gave lower absolute CVR values compared with method 1, and the value obtained with method 4 was dramatically lower. Our findings indicate that care must be taken to ensure that CVR is measured over the linear range of the CBF-CO 2 dose-response curve, avoiding hypocapnic conditions.