Testing the null hypothesis of uncoupling between mean arterial pressure and mean cerebral blood velocity in health and pathology via different surrogate strategies

OBJECTIVE: The dynamic cerebral autoregulation (dCA) limits variability of mean cerebral blood velocity (MCBv) despite mean arterial pressure (MAP) variations through a myriad of nonlinear mechanisms. However, dCA operates in association with the flow-to-pressure pathway. This study aims at characterizing the closed loop MCBv-MAP relationship by separating the dependence of MAP on MCBv from that over the reverse pathway using different surrogate approaches. APPROACH: Analyses were carried out in 26 healthy controls (HCs, age: 43±11 yrs, 13 males, 13 females) and 48 severe aortic valve stenosis patients undergoing surgical aortic valve replacement (SAVR, age: 62±14 yrs; 35 males, 13 females) before and after surgery. Active standing (STAND) from supine resting (REST) was exploited to challenge dCA. A state space correspondence method based on model-free cross-predictability was exploited to estimate the degree of MCBv dependence on MAP and vice versa and two different types of surrogates destroying nonlinear components or preserving them as much as possible were utilized. MAIN RESULTS: We found that: i) STAND deteriorates dCA in HCs; ii) in SAVR patients STAND does not affect dCA either before or after surgery, but a pre-surgery activation of flow-to-pressure link is present at REST; iii) in HCs preserving nonlinear dynamics when testing the significance of the pressure-to-flow link provides results different from those derived while maintaining exclusively linear dynamics. SIGNIFICANCE: Results stressed the pathophysiological relevance of applying a nonlinear directional approach to disentangle closed loop MCBv-MAP relationship and suggest that conclusions might depend on the strategy adopted to generate surrogates.