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Dynamic interdependencies within and between physiological systems and subsystems are key for homeostatic mechanisms to establish an optimal state of the organism. These interactions mediate regulatory responses elicited by various perturbations, such as the high-pressure baroreflex and cerebral autoregulation, alleviating the impact of orthostatic stress on cerebral hemodynamics and oxygenation. The aim of this study was to evaluate the responsiveness of the cardiorespiratory-cerebrovascular networks by capturing linear and nonlinear interdependencies to postural changes. Ten young healthy adults participated in our study. Non-invasive measurements of arterial blood pressure (from that cardiac cycle durations were derived), breath-to-breath interval, cerebral blood flow velocity (BFV, recorded by transcranial Doppler sonography), and cerebral hemodynamics (HbT, total hemoglobin content monitored by near-infrared spectroscopy) were performed for 30-min in resting state, followed by a 1-min stand-up and a 1-min sit-down period. During preprocessing, noise was filtered and the contribution of arterial blood pressure was regressed from BFV and HbT signals. Cardiorespiratory-cerebrovascular networks were reconstructed by computing pair-wise Pearson-correlation or mutual information between the resampled signals to capture their linear and/or nonlinear interdependencies, respectively. The interdependencies between cardiac, respiratory, and cerebrovascular dynamics showed a marked weakening after standing up persisting throughout the sit-down period, which could mainly be attributed to strikingly attenuated nonlinear coupling. To summarize, we found that postural changes induced topological changes in the cardiorespiratory-cerebrovascular network. The dissolution of nonlinear networks suggests that the complexity of key homeostatic mechanisms maintaining cerebral hemodynamics and oxygenation is indeed sensitive to physiological perturbations such as orthostatic stress.

Hemoglobin-based oxygen carriers (HBOCs) were developed with the aim of substituting transfusions in emergency events. However, they exhibit adverse events, such as nitric oxide (NO) scavenging, vasoactivity, enhanced platelet aggregation, presently hampering their clinical application. The impact of two prototypical PEGylated HBOCs, Euro-PEG-Hb and PEG-HbO2, endowed by different oxygen affinities and hydrodynamic volumes, was assessed on the cerebrocortical parenchymal microhemodynamics, and extravasation through the blood-brain-barrier (BBB) by laser speckle contrast imaging (LSCI) method and near-infrared (NIR) imaging, respectively. By evaluating voxel-wise cerebrocortical red blood cell velocity, non-invasively for its mean kernel-wise value ( v ¯ RBC ), and model-derived kernel-wise predictions for microregional tissue hematocrit, THt, and fractional change in hematocrit-corrected vascular resistance, R’, as measures of potential adverse effects (enhanced platelet aggregation and vasoactivity, respectively) we found i) no significant difference between tested HBOCs in the systemic and microregional parameters, and in the relative spatial dispersion of THt, and R’ as additional measures of HBOC-related adverse effects, and ii) no extravasation through BBB by Euro-PEG-Hb. We conclude that Euro-PEG-Hb does not exhibit adverse effects in the brain microcirculation that could be directly attributed to NO scavenging.

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