The objective of this research is to make pulsatile heart replacement systems available to smaller adult patients. This is a non-trivial matter, because reduction in the size of a pulsatile blood pump affects (1) the fluid dynamics of the pump, (2) the energetics of the pump and actuator, and (3) the stresses experienced by the blood contacting materials. Thus, we consider studies such as those described here to be critical to the availability of artificial hearts and pulsatile ventricular assist devices for the full spectrum of patients. We propose to study the underlying principles of pump size reduction through three specific aims: FIRST, Utilize an integrated method of CFD modeling, experimental fluid dynamics techniques, in vitro testing and in vivo studies to significantly improve reduced size blood pumps and energy converter designs utilizing physical design constraints. These modeling and in-vitro studies will be used to predict system performance. The significance of these findings will be assessed through in vivo studies in calves. Thrombogenesis will be assessed through hematology studies, platelet activation studies, and explant analysis. Platelet and fibrin adhesion will be quantified by post explant gross exam, histological examination and multi-scale surface analysis. SECONDLY, we have developed relationships governing energetic performance of the system, utilizing a computer simulation of the energy converter, blood pump, circulation, controller, and energy transmission system. We will tailor control of actuator movement to improve fluid mechanics. The results of these studies will also be evaluated in-vitro and in-vivo. THIRDLY, we will refine and utilize improved FEA models necessary for predicting and minimizing stresses in biomaterials, so that durability of reduced-size devices is not adversely affected by pump scaling. We expect that this research will be broadly applicable to pulsatile blood pump design, especially by improving our understanding of the relationships between surface effects, fluid dynamics, and thrombogenesis in a complex, time-varying flow field. This work requires a multi-disciplinary effort in surgery, engineering, fluid mechanics, and hematology, with the means to efficiently manufacture blood pump systems and carry out the necessary in vitro and in vivo studies. [unreadable] [unreadable] PUBLIC HEALTH RELEVANCE: This research combines computational fluid dynamics, experimental fluid dynamics, systems modeling, finite element analysis, in vitro and in vivo techniques to develop a comprehensive method for the design of small blood pumps. [unreadable] [unreadable] [unreadable]