Parab, Shambhavi Bajrang
(2024)
Treprostinil Protects Liver from Circulatory Death Donors- Evidence Using Normothermic Machine Perfusion.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Liver transplantation (LT) is the only treatment for End Stage Liver Disease. However, currently organ shortage is the major clinical limitation in liver transplantation. Attempts have been made to bridge the gap for organ shortage by utilizing extended criteria donors such as donation after circulatory death (DCD). But these marginal livers are subjected to Ischemia/Reperfusion (I/R) injury and require specialized measures for organ preservation and treatment. The overall objective of this study is to evaluate the impact of treprostinil, on the viability of livers obtained after circulatory death, using ex vivo normothermic machine perfusion (NMP).
In this study we subjected male Sprague-Dawley rats to 30 minutes of warm ischemia time in situ, mimicking the process of DCD-LT. Livers were then procured, cold-preserved until mounted onto the ex vivo NMP. For 4 hours, DCD livers underwent NMP with/ without 20 ng/mL treprostinil in the perfusate. Inflow and outflow perfusates were collected at different time points during the NMP for assessing several hepatic and biliary viability parameters.
Treprostinil was effective in minimizing I/R injury from DCD rat livers. The levels of AST and ALT were significantly higher in DCD control group, while in DCD treprostinil livers they reduced by 30% and 50% of DCD-control, respectively. The Portal Vein Pressure (PVP) increased in DCD control group, in contrast, vascular resistance in DCD treprostinil livers was significantly lower. Livers perfused with treprostinil produced significantly more volume of bile, compared to the control group. The other biliary viability parameters such as bile pH and bile LDH, also showed improvement in DCD-treprostinil group as compared to the DCD control and was close to normal livers. Treprostinil supplementation during NMP of DCD livers significantly reduced I/R injury and improved graft function.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Parab, Shambhavi Bajrang | sbp40@pitt.edu | SBP40 | |
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| ETD Committee: |
|
| Date: |
25 April 2024 |
| Date Type: |
Publication |
| Defense Date: |
8 April 2024 |
| Approval Date: |
25 April 2024 |
| Submission Date: |
16 April 2024 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
64 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Liver Transplantation, Donor After Circulatory Death, Treprostinil, Ischemia/ Reperfusion injury, organ preservation |
| Date Deposited: |
25 Apr 2024 15:42 |
| Last Modified: |
25 Apr 2024 15:42 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/46133 |
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