Limitation of cerebral blood flow by increased venous outflow resistance in elevated ICP

Extensive investigation and modeling efforts have been dedicated to cerebral pressure autoregulation, which is primarily regulated by the ability of the cerebral arterioles to change their resistance and modulate cerebral blood flow (CBF). However, the mechanisms by which elevated intracranial pressure (ICP) leads to increased resistance to venous outflow have received less attention. We modified our previously described model of intracranial fluid interactions with a newly developed model of a partially collapsed blood vessel, which we termed the "flow control zone" (FCZ). We sought to determine the degree to which ICP elevation causing venous compression at the FCZ becomes the main parameter limiting CBF. The FCZ component was designed using nonlinear functions representing resistance as a function of cross-sectional area and the pressure-volume relations of the vessel wall. We used our previously described swine model of cerebral edema with graduated elevation of ICP to calculate venous outflow resistance and a newly defined parameter, the cerebral resistance index (CRI), which is the ratio between venous outflow resistance and cerebrovascular resistance. Model simulations of cerebral edema and increased ICP led to increased venous outflow resistance. There was a close similarity between model predictions of venous outflow resistance and experimental results in the swine model (cross-correlation coefficient of 0.97, a mean squared error of 0.087, and a mean absolute error of 0.15). CRI was strongly correlated to ICP in the swine model (r² = 0.77, P = 0.00012, 95% confidence interval [0.15, 0.45]). A CRI value of 0.5 was associated with ICP values above clinically significant thresholds (24 mmHg) in the swine model and a diminished capacity of changes in arteriolar resistance to influence flow in the mathematical model. Our results demonstrate the importance of venous compression at the FCZ in determining CBF when ICP is elevated. The cerebral resistance index may provide an indication of when compression of venous outflow becomes the dominant factor in limiting CBF following brain injury.NEW & NOTEWORTHY The goal of this study was to investigate the effects of venous compression caused by elevated intracranial pressure (ICP) due to cerebral edema, validated through animal experiments. The flow control zone model highlights the impact of cerebral venous compression on cerebral blood flow (CBF) during elevated ICP. The cerebral venous outflow resistance-to-cerebrovascular resistance ratio may indicate when venous outflow compression becomes the dominant factor limiting CBF. CBF regulation descriptions should consider how arterial or venous factors may predominantly influence flow in different clinical scenarios.