Instability in vascular adaptation can explain the development of cerebral
arteriovenous malformations
C. M. Quick, T. Hashimoto, and W. L. Young
XIV Congress, Cardiovascular System Dynamics Society, Baltimore, MD, 2000
Abstract
The present work presents an explanation for the genesis of cerebral arteriovenous
malformations (AVMs) derived from mathematical modeling found in the basic
science literature. A modeling approach is particularly useful, because
the early natural history of AVM development is unknown. Investigators
have recently had great success using mathematical models with the same phenomenological
behavior of actual vascular beds to explore the relationship of structure
to function in normal vascular beds. However, when they first explored
how vascular beds adapt to set endothelial shear stress at appropriate levels,
vessels of the model either degenerated to zero radius or grew into large
arteriovenous shunts. The resultant vascular structure, predicted from
these early models, were similar to that of AVMs. This flaw was prevented
when flow regulation (or autoregulation) was added to the models. We
propose that this artifact of the early incomplete models may help explain
the development of AVMs. To illustrate, we developed a simple hemodynamic
model consisting of three parts: 1) bifurcating arterial and venous trees,
2) an empirical description of the microvasculature, and 3) a target shear
stress depending on pressure. This simple model has the minimum requirements
to explain qualitatively the observed structure and hemodynamics of normal
vasculature. Removing local control of blood flow causes the model
to become structurally unstable, yielding a structure and behavior similar
to AVMs; the smaller vessels disappear, and the larger vessels grow into
arteriovenous shunts. The proposed mechanism has broad implications,
and may be applicable to other organ systems, such as lung. With the
insight gained from this modeling approach, very specific, focused experiments
and lines of inquiry are suggested.