Modeling acute and chronic vascular adaptations following a major arterial occlusion

The occlusion of major arterioles can lead to serious health complications such as peripheral arterial disease and ischemic stroke.  Pre-existing collateral vessels provide alternate routes for blood flow when a major artery is occluded, thereby supplying oxygen to tissue regions downstream of an occlusion. However, the extent to which collateral vessels can compensate for a major arterial occlusion is not fully understood.  Mathematical modeling provides a useful tool to predict the role of collateral arteries in flow compensation following occlusion.  In this work, a vascular wall mechanics model is applied to a rat hindlimb model of femoral arterial occlusion and a human brain model of middle cerebral arterial occlusion.  The model incorporates both acute vascular responses (e.g., immediate vessel constriction and dilation) and chronic vascular responses (e.g., arteriogenesis and angiogenesis). In the hindlimb model, the model predicts that acute responses only restore post-occlusion flow to 24% of non-occluded blood flow, while the addition of chronic responses yields blood flow that is 84% of the non-occluded level.  The model is adapted to a simplified geometry of the cerebral circulation to assess the role of leptomeningeal collaterals in compensating for a middle cerebral arterial occlusion. This model predicts a 62% reduction in oxygen saturation in the region distal to the occlusion; however, the saturation post-occlusion can be approximately doubled with the recruitment of six additional leptomeningeal collaterals. Ultimately, the model predictions indicate that interventions which enhance collateral arteriogenesis would have the greatest potential for restoring blood flow to healthy levels.

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