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

Extensive research focuses on cerebral pressure autoregulation, primarily regulated by changes in cerebral arterioles resistance that modulate cerebral blood flow (CBF). However, the mechanisms by which elevated intracranial pressure (ICP) affects venous outflow resistance (VOR) have received less attention. Previously described model of intracranial fluid interactions was modified with a model of a partially-collapsed blood vessel, termed the Flow Control Zone (FCZ). We sought to determine the degree to which ICP elevation, causing venous compression at the FCZ, limits CBF. 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 a swine model of cerebral edema with graduated elevation of ICP to calculate VOR and the cerebral resistance index (CRI), which is the ratio between VOR and cerebrovascular resistance (CVR). Model simulations showed increased VOR with elevated ICP and a close similarity between model predictions of VOR and experimental results in the swine model (cross-correlation coefficient of 0.97). CRI was strongly correlated to ICP in the swine model (r 2 =0.77, p<0.0001). A CRI value of 0.5 was associated with ICP values above clinically significant thresholds (23.7 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, suggesting that CRI may indicate when compression of venous outflow becomes the dominant factor in limiting CBF following brain injury.