Heart failure results in significant morbidity and mortality for those afflicted. The current gold standard treatment is allogenic heart... Show moreHeart failure results in significant morbidity and mortality for those afflicted. The current gold standard treatment is allogenic heart transplantation, however insufficient supply of donor organs limits the effectiveness of this treatment to ideal candidates. This has led to interest in mechanical circulatory support. The most recent generation of devices are smaller, continuous-flow devices with increased durability compared to their predecessors. However, these new devices exhibit increased rates of hemostatic events – both thromboembolic and hemorrhagic. This thesis details an in vivo evaluation of hemostatic parameters in a bovine animal model to evaluate the effect of the ventricular assist device (VAD), and compares these results to what has been seen clinically. Most importantly this thesis has found that bovines do not experience pathophysiologic degradation of high molecular weight Von Willebrand Factor (VWF) as a result of VAD placement, whereas this complication is well documented in humans. This is due to a decreased sensitivity to shear stress induced cleavage of VWF in bovines when compared to humans, as demonstrated in this thesis. Due to the inability to replicate clinical conditions with the bovine animal model, this thesis develops an alternative methodology using an in vitro flow loop using the same human donor blood on all pumps tested. This methodology eliminates the need for interspecies extrapolation; allows for more direct comparisons by eliminating donor variation; and is both cheaper and faster than animal models. This methodology could provide an invaluable option for evaluating hemostatic effects of various pump design parameters. Ph.D. in Biomedical Engineering, July 2011 Show less
