Limitation of Cerebral Blood Flow by Increased Venous Outflow Resistance in Elevated ICP

Abstract

Abstract Background Extensive investigation and modeling efforts have been dedicated to cerebral pressure autoregulation, which is primarily regulated by the cerebral arterioles ability 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. Methods The FCZ component was designed using non-linear 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 (VOR) and a newly defined parameter, the cerebral resistance index (CRI), which is the ratio between venous outflow resistance and cerebrovascular resistance. Results 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). CRI was strongly correlated to ICP in the swine model (r2 = 0.77, p < 0.0001). A CRI value of 0.5 was associated with ICP values above clinically significant thresholds (23.7 mm Hg) in the swine model and a diminished the capacity of changes in arteriolar resistance to influence flow in the mathematical model. Conclusions 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.