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Immunological and hemostatic responses to ventricular assist device support

Woolley, Joshua (2014) Immunological and hemostatic responses to ventricular assist device support. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Ventricular assist devices (VADs) are critical in the treatment of advanced heart failure, but continue to be plagued by infection, bleeding and thrombosis. Immunity may be affected by VADs, though most paradigms were developed in older-generation pumps and may not currently be applicable. Similarly, hemostasis and platelets may be impacted by device type, though the patient’s health may also influence outcomes. Temporal immune cell activation and thrombosis biomarkers levels were evaluated across several contemporary pumps. This relationship was further studied in vitro through development of a method for visualizing cellular deposition onto opaque materials. An improved understanding of the cellular effects of VADs was sought through a comparative evaluation of these pumps, and this understanding may aid in the development of predictive indices of adverse events and influence future device design.
Patients implanted with a currently-utilized VAD did not experience changes to adaptive immunity reported with previous-generation devices. However, infection was still an ongoing risk for these patients. Further investigation found the impact of VADs on immunity was greater than that of similar surgeries, especially among innate immunity. Granulocyte activation was elevated following VAD implantation, and was significantly pronounced in one model, suggesting an influence of design on immune cells. Granulocyte activation promotes extravasation and apoptosis, suggesting a pathway for decreased cellular immunity.
Pre-operative hepatic dysfunction had immediate and long lasting hemostatic effects on VAD patients. Model for End-stage Liver Disease (MELD) score was found to be a positive pre-operative predictor of post-implant bleeding, blood product consumption and elevation of thrombosis biomarkers. MELD score was also found to be a stronger predictor of immediate post-operative bleeding than device type, underscoring the importance of patient pre-operative health on post-operative outcomes.
With this difficult hemostatic environment, improvement of the blood-contacting surfaces of rotary VADs may reduce complications. A flow chamber for real-time visualization of platelet deposition onto surfaces of opaque VAD materials under physiologically-relevant conditions was developed. This was accomplished through the novel combination of fluorescently-marked platelet-rich-plasma and translucent hemoglobin-depleted red blood cells. This method enables the hemocompatibility assessment of a wide range of implantable materials.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWagner, Williamwagnerwr@upmc.eduWAGNER
Committee MemberAntaki,
Committee MemberBorovetz, Harveyborovetzhs@upmc.eduBOROVETZ
Committee MemberKormos, Robertkormosrl@upmc.eduKORMOS
Committee MemberWearden,
Date: 16 June 2014
Date Type: Publication
Defense Date: 20 March 2014
Approval Date: 16 June 2014
Submission Date: 31 March 2014
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 182
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: ventricular assist device; biomaterials; biocompatibility
Date Deposited: 16 Jun 2014 18:52
Last Modified: 19 Dec 2016 14:41


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