Defining the physiology of cerebral autoregulation

Abstract

Cerebrovascular autoregulation is critical for neurophysiologic health; however, our understanding of the mechanisms is limited. Recent studies show the importance of noradrenergic (NA) and cholinergic (ACh) pathways, though less so for myogenic (MYO). There have been no attempts to consolidate these effectors of cerebral flow into a comprehensive model. Moreover, most work relies on linear approaches that are limited when applied to this inherently nonlinear function. Therefore, we used our projection pursuit method to explore alterations in the relation between pressure (Finapres) and cerebral flow (Doppler) in unblocked (n=48) and blocked (NA, n=11; ACh, n=9; MYO, n=16) states. Differences in autoregulation caused by blockade were used to derive a predictive model for autoregulation in the unblocked state. Projection pursuit provided gain and range of autoregulation as well as the pressure‐flow relations above and below this range. NA blockade markedly linearized the autoregulatory response whereas ACh blockade primarily increased the autoregulatory range by 50%. In contrast to what has been found with linear assessments, MYO blockade reduced the pressure‐flow relations above and below the autoregulatory region. Thus, the predictive model used the contribution of each individual mechanism to achieve an integrated understanding of cerebral autoregulatory control. Support: NIH HL093113.