Influence of CO 2 on neurovascular coupling: interaction with dynamic cerebral autoregulation and cerebrovascular reactivity

PaCO 2 affects cerebral blood flow ( CBF ) and its regulatory mechanisms, but the interaction between neurovascular coupling ( NVC ), cerebral autoregulation ( CA ), and cerebrovascular reactivity to CO 2 ( CVR ), in response to hypercapnia, is not known. Recordings of cerebral blood flow velocity ( CBF v), blood pressure ( BP ), heart rate, and end‐tidal CO 2 ( E t CO 2 ) were performed in 18 subjects during normocapnia and 5% CO 2 inhalation while performing a passive motor paradigm. Together with BP and E t CO 2 , a gate signal to represent the effect of stimulation was used as input to a multivariate autoregressive‐moving average model to calculate their separate effects on CBF v. Hypercapnia led to a depression of dynamic CA at rest and during stimulation in both hemispheres ( P  <   0.02) as well as impairment of the NVC response, particularly in the ipsilateral hemisphere ( P  <   0.01). Neither hypercapnia nor the passive motor stimulation influenced CVR . Dynamic CA was not influenced by the motor paradigm during normocapnia. The CBF v step responses to each individual input ( BP , E t CO 2 , stimulation) allowed identification of the influences of hypercapnia and neuromotor stimulation on CA , CVR , and NVC , which have not been previously described, and also confirmed the depressing effects of hypercapnia on CA and NVC . The stability of CVR during these maneuvers and the lack of influence of stimulation on dynamic CA are novel findings which deserve further investigation. Dynamic multivariate modeling can identify the complex interplay between different CBF regulatory mechanisms and should be recommended for studies involving similar interactions, such as the effects of exercise or posture on cerebral hemodynamics.