Computational and biological studies of mechanical prophylaxis against deep venous thrombosis

Abstract

Deep vein thrombosis (DVT) of the lower extremity and induced pulmonary embolism are common complications resulting from prolonged periods of bed-rest or immobilization of the limbs. One of the most effective methods of prophylaxis against DVT is external pneumatic compression (EPC). In spite of its wide acceptance as an effective means of prophylaxis, its mechanism remains poorly understood and optimal compression conditions have not been defined. Understanding the biological consequences of EPC is an important goal for optimizing the performance of compression device and providing guidance for clinical use. In the first part of this thesis, a computational model of the leg was developed to simulate hemodynamic conditions under EPC and the influence of different modes of compression were analyzed and compared. Then, a new in vitro cell culture system was developed that can be used to examine the effect of hemodynamic conditions during EPC on endothelial cell (EC) function. The biologic response was assessed through changes in cell morphology and the expression of various pro-thrombotic and anti-thrombotic factors related to EC.

(cont.) The results show that intermittent flow associated with EPC up-regulates EC fibrinolytic potential and vasomotor function. Using DNA microarray technology, the data of thrombo-regulatory factors indicates that EC gene expression shifts toward anti-thrombotic vs. pro-thrombotic under EPC. Finally, Nitric Oxide (NO), an important regulator of vasomotor and platelet functions was studied in detail under various cycles of EPC. The results show that NO production and eNOS mRNA respond differentially to modes of EPC. Further exploration using the system can potentially reveal the optimum combination of forces to better regulate thromboresistant effects desired for DVT prophylaxis.