Johnson Jr., Carl A
(2010)
Preclinical Biocompatibility Assessment of Pediatric Ventricular Assist Devices.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
A number of heart assist devices including the PediaFlowTM ventricular assist device (VAD), a magnetically levitated mixed flow rotary blood pump, and the Levitronix® PediVAS™, an extracorporeal magnetically levitated centrifugal blood pump are under development to address the urgent need for mechanical circulatory support suitable for children in heart failure. VADs are associated with a host of biological complications including bleeding, thromboembolism, and infection. The biocompatibility of these new devices must be characterized in a preclinical model (juvenile ovines) to ensure their safety and efficacy in children. However, biocompatibility studies in ovines are limited due to a lack of available assays. Flow cytometric assays were developed to detect ovine platelet activation and function. These assays were applied during in vitro assessment of potential biomimetic coatings for the blood contacting surfaces of pediatric VADs. These assays were then applied in vivo in 5 lambs undergoing a VAD sham surgical procedure for 30 days duration, in 20 lambs implanted with the Levitronix PediVAS for 30 days duration, and in 8 lambs implanted with the three design iterations of the PediaFlow VAD ranging from 6 - 72 days duration. The sham surgical procedure enabled characterization of the effects of the implant surgery on platelet activation. Platelet activation was reduced on surfaces that received a biomimetic coating compared to uncoated surfaces which was in agreement with platelet deposition results. Platelet activation levels rose post-operatively in the sham animals and returned to pre-operative levels at approximately two weeks. In PediaFlow and Levitronix implanted animals platelet activation also rose post-operatively and typically returned to baseline levels. In these implants platelet activation consistently rose following pump or animal complications. In a subset of studies platelet activation was elevated for the duration of the study and this high level of activation generally coincided with increased kidney infarcts or thrombus deposition in the cannulae at necropsy. Overall, the blood biocompatibility of the Levitronix PediVAS and the PediaFlow VAD as represented by a low level of platelet activation observed in the majority of studies is encouraging for the potential clinical use of these devices. The ability of the developed platelet activation assays to differentiate between surface coatings, and to discern trends with respect to pump complications and kidney infarcts following VAD implant demonstrate its utility in assessing the blood biocompatibility of pediatric heart assist devices.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Johnson Jr., Carl A | caj4@pitt.edu | CAJ4 | |
|
| ETD Committee: |
|
| Date: |
30 September 2010 |
| Date Type: |
Completion |
| Defense Date: |
19 July 2010 |
| Approval Date: |
30 September 2010 |
| Submission Date: |
15 July 2010 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
biocompatibility assessment; flow cytometry; Levitronix PediVAS; ovine platelet activation; PediaFlow; pediatric ventricular assist devices |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-07152010-235631/, etd-07152010-235631 |
| Date Deposited: |
10 Nov 2011 19:51 |
| Last Modified: |
19 Dec 2016 14:36 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8392 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[feed]](/images/feed-icon-32x32.png){kind=icon}