The development and application of an in vitro model of coronary lesion thrombosis

Abstract

Thrombosis is an initiating response to vascular injury. Physiologically, this process aids in the repair and remodeling of the vessel wall. However, if left unchecked, luminal occlusion may rapidly occur. The coronary vascular bed is a life-sustaining environment in which pathological thrombosis can lead to devastating outcomes such as acute coronary syndromes or post-interventional thrombosis. In order to study these coronary thrombotic reactions, it is essential to consider the physical environment in which they occur. We have developed an in vitro method for creating pulsatile flows to mimic the coronary hernodynamic setting on a beat-to-beat basis. Furthermore, he have developed techniques and protocols to parametrically vary both the biological and physical aspects of thrombosis and in doing so, have investigated the effects of real-world temporal and spatial flow perturbations on local site platelet adhesion. Not only do such variations create quantitative differences in local reactions, but qualitative differences as well as various receptors must interact to create stable adhesions in a given hemodynamic environments. These findings have implications on the propensity for certain individuals to form clot under certain conditions, as well as the environment-dependent efficacy of various clinically relevant anti-thrombotic strategies.