Influence of Flow-induced Mechanical Forces on Thrombolysis Studied by MR and Optical Microscopy

Introduction: Thromobolysis remains the mainstay in treatment of ischaemic cerebrovascular stroke, haemodynamically significant pulmonary embolism, and retains a role in the treatment of myocardial infarction in hospitals that do not provide emergency percutaneous transluminal angioplasty. Biochemo-mechanical mechanisms of thrombolysis are not yet entirely understood. In the literature, it is believed that thrombolysis is predominantly a biochemical process in which thrombolytic agent (rt-PA) selectively activates plasminogen bound to fibrin into its active form (plasmin) that cleaves the fibrin meshwork and dissolves the clot [1]. However, the thrombolytic process cannot progress without an adequate transport of the thrombolytic agent into the clot. This is a diffusion process in the absence of blood flow (occlusive clots) and reverts into a perfusion process when the recanalization channel is formed through the clot (non-occlusive clots). The second, perhaps even more important effect of flow are mechanical forces of the flowing blood to the surface of the clots. Both flow induced mechanisms, i.e., the faster thrombolytic agent delivery to the clot and mechanical clot degradation, act in parallel and significantly promote thrombolysis [2]. In this study, MR microscopy was used to study the delivery of thrombolytic agent into the clot and also its dissolution followed after. The MR microscopy study was complemented by optical microscopy of the same process.