Bleeding and thromboembolism remain major complications of ventricular assist device (VAD) support. The amount of biocompatibility information that may be collected during preclinical studies is limited due to a lack of available assays, leaving the evaluation of investigational devices incomplete. To address these issues, flow cytometric assays were developed to quantify bovine circulating activated platelets, platelet microaggregates, platelet-leukocyte aggregates, and monocytes expressing tissue factor. Platelet lifespan was determined using an ex vivo biotinylation technique.
These assays were applied in 50 animals receiving the Nimbus/Heartmate II axial flow VAD, 29 receiving the SunMedical EVAHEART centrifugal VAD, over 20 animals receiving a variety of other cardiovascular devices, and eight animals that underwent a sham VAD implantation procedure. The results demonstrated significantly increased circulating activated platelets and leukocytes, and cell aggregates following VAD implantation, which then usually declined to a lower but still significantly elevated level. Deviations from this pattern were observed in several pumps with obstructive thrombi in the blood flow path. Platelet life span decreased and platelet consumption correspondingly increased. The sham studies demonstrated that the effects of the implant procedure abated within three weeks. Thus, the ongoing platelet and leukocyte activation and aggregation, and decreased platelet life span could be attributed to the VADs, even while accounting for surgical effects.
To identify the potential causes of the observed cellular activation, VAD surface modifications, revolutions per min increases, and anticoagulant regimen changes were evaluated in vivo. Two blood-shearing devices were constructed to investigate the effects of the supraphysiologic shear field within rotary VADs, although heat generation and sealing issues limited their effectiveness. Flow visualization of the Heartmate II VAD revealed vortices developed at low flow rates, frequently encountered in vivo.
In conclusion, the propensity of cardiovascular devices to activate platelets and leukocytes was quantified, while accounting for the effects of the implant procedure. Through in vivo and in vitro investigations, it was demonstrated that the blood-contacting surface and adverse flow effects each contributed to the observed cellular activation. Thus, applying novel biocompatibility assays to preclinical studies, including those evaluating design enhancements and refinements, may be used to develop safer cardiovascular devices.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04062006-102142 |
| Date | 02 June 2006 |
| Creators | Snyder, Trevor Arnoult |
| Contributors | Franklin A. Bontempo, Robert L. Kormos, James F. Antaki, William J. Federspiel, Harvey S. Borovetz, William R. Wagner |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04062006-102142/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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