Delivery of Plasmin During Machine Perfusion or Cold Storage Flush Improves Early Transplant Outcomes in aRat Dcd Liver Transplant Model
1Duke Division of Abdominal Transplant Surgery, Duke Ex-Vivo Organ Lab (DEVOL), Durham, NC, 2Duke Division of Surgical Sciences, Pollara lab, Durham, NC, 3Bioscience Industrial Group, Grifols R&D, Durham, NC
Meeting: 2022 American Transplant Congress
Abstract number: 368
Keywords: Bile duct, Ischemia, Machine preservation, Rat
Topic: Basic Science » Basic Science » 15 - Machine Perfusion and Organ Rehabililtation - Basic
Session Information
Session Name: Machine Perfusion and Organ Rehabililtation - Basic
Session Type: Rapid Fire Oral Abstract
Date: Monday, June 6, 2022
Session Time: 5:30pm-7:00pm
Presentation Time: 6:50pm-7:00pm
Location: Hynes Ballroom A
*Purpose: Ischemic injury of the peribiliary glands and vascular plexus has been described in DCD livers and correlates with the development of cholangiopathy. Investigators have demonstrated improved biliary histology with plasma and tissue plasminogen activator treatment during machine perfusion of discarded DCD livers. However, no studies have yet evaluated the effect of thrombolysis on post-transplant graft function. The development of a stabilized plasmin product simplifies thrombolysis therapy during cold storage and machine perfusion. In this study, we hypothesized that the delivery of plasmin during machine perfusion and cold storage would enhance post-transplant graft function in a rat DCD liver transplant model.
*Methods: We performed DCD liver transplants in rats using 30 minutes of warm ischemic injury. Livers were preserved by either 1hr of acellular room temperature machine perfusion (n=16) or static cold storage (n=12). Plasmin (experimental) or albumin (control) was delivered in blinded fashion to a final concentration of 0.1mg/ml into either 200ml of machine perfusion solution or HTK cold storage flush. Following transplantation, recipient survival was assessed at 24 hours and survivors were sacrificed for assessment of post-transplant graft function and histology.
*Results: After 1h of cold storage in the presence of plasmin, a significant survival benefit at 24hrs (80% vs 14.2% survival, P=0.0293) post-transplantation was observed. The low number of survivors in the control group prohibited meaningful comparison of biliary injury levels. After 1h of machine perfusion, there was no survival benefit observed for plasmin-treated vs. untreated grafts. However, there was a significant decrease in 24h serum alkaline phosphatase with plasmin administration (mean 216.6 vs 56 U/L, P=0.0006). In addition, glucose homeostasis was improved in recipients of plasmin-treated grafts at 24h (mean 163 vs. 82. 3mg/dl, P= 0.0067). No overt bleeding complications were observed post-transplant in either modes of organ preservation.
*Conclusions: These findings demonstrate that administration of plasmin during machine perfusion or static cold storage may improve overall graft function in the setting of DCD liver transplantation.
To cite this abstract in AMA style:
Abraham N, Zhang M, Cray P, Neill R, Cywinska G, Migaly J, Kahan R, Pontula A, Penaflor J, Gao Q, Samy KP, Pollara JJ, Novokhatny V, Hartwig MG, Barbas AS. Delivery of Plasmin During Machine Perfusion or Cold Storage Flush Improves Early Transplant Outcomes in aRat Dcd Liver Transplant Model [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/delivery-of-plasmin-during-machine-perfusion-or-cold-storage-flush-improves-early-transplant-outcomes-in-arat-dcd-liver-transplant-model/. Accessed May 8, 2025.« Back to 2022 American Transplant Congress