The objective of this research is to develop improved analytical and experimental methods used in a structured approach for the design of blood pumps with reduced potential for adverse events. We propose to continue our efforts focusing on the development of a computational platform using an open source code that integrates and couples shear-induced blood damage, thrombosis susceptibility potential, platelet activation, and thrombosis models simultaneously during the design process. Currently, only hemolysis models are used in the design phase and platelet activation used in rare cases, but neither has been integrated into a single computational model simultaneously. Our use of large eddy simulation computational fluid dynamics (CFD) provides a flow field capturing much of the turbulent flow field. We will apply this structured approach on a prototype bladed rotary ventricular assist device (VAD) that we are developing. To accomplish these goals, we will focus on the following specific aims: 1. Integrate a newly developed shear-induced blood damage model based upon dissipation (7), a thrombosis susceptibility potential (TSP) (8-10), and a platelet activation model (11) into a single computational platform to design a rotary blood pump incorporating the interaction of the VAD and native heart pulsatility. This research is intended to culminate in inclusion of a continuum-based macroscopic thrombosis model to refine the pump design. 2. Develop a continuum-based macroscopic thrombosis model for both laminar and turbulent flow and shear induced platelet activation that will be used to refine the pump design. The thrombosis model will be validated through in vitro platelet adhesion studies using a rotating disk system (RDS), an in vitro backward facing step (BFS) model using whole blood, and clinical LVAD patients. 3. Perform in vivo animal studies of a prototype rotary VAD system in non-anticoagulated animals to a) assess location, severity, and time course of thrombosis and embolization, b) study the effect of pump speed and pulsatile flow, and c) measure platelet activation, global coagulation, and hemolysis. This research will yield improved design and analysis tools in a structured approach that will be applicable to a broad range of blood pumps and blood contacting cardiovascular devices.

Public Health Relevance

Although left ventricular assist devices substantially improve survival in patients with end stage heart failure, pump thrombosis and thromboembolism result in significant morbidity. The goal of this research is to develop computational methods to predict and minimize thrombosis, through the use of a physics-based blood damage and thrombosis model which includes turbulence, validated through in vitro and in vivo studies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL136369-01A1
Application #
9446339
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Baldwin, Tim
Project Start
2018-05-25
Project End
2022-04-30
Budget Start
2018-05-25
Budget End
2019-04-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Surgery
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033