Modeling the Mechanisms of Non-Neurogenic Dynamic Cerebral Autoregulation

Objective: Dynamic cerebral autoregulation (dCA) refers to a collection of mechanisms that act to maintain steady state cerebral blood flow (CBF) near constant despite changes in arterial blood pressure (ABP), but which is known to become impaired in various cerebrovascular diseases. Currently, the mechanisms of dCA and how they are affected in different physiological conditions are poorly understood. The objective of this study was to disentangle the magnitudes and time scales of the myogenic and metabolic responses of dCA, in order to investigate how each mechanism is affected in impaired dCA. Methods: A physiological model of dCA was developed, where both the myogenic and metabolic responses were represented by a gain and time constant. Model parameters were optimized with pressure-flow impulse responses under normocapnic, thigh cuff, and hypercapnic conditions. The impulse responses were derived by applying transfer function analysis (TFA) to experimental recordings of ABP (Finapres), end-tidal CO₂ (capnograph), and CBF velocity (transcranial doppler ultrasound in bilateral middle cerebral arteries). Results: The myogenic gain to time constant ratio was significantly smaller (p-values < 0.001 using both univariate and multivariate TFA), and the metabolic time constant was significantly larger (p-values < 0.001 using both univariate and multivariate TFA) in hypercapnia compared to normocapnia. Conclusion: Both the myogenic and metabolic responses were shown to be affected in impaired dCA, and the metabolic response was shown to be slowed down. Significance: This study contributes to the understanding of the complexities of dCA and how it is affected in different physiological conditions.