Development of a Prolonged Warm Ex Vivo Perfusion Model for Kidneys Donated after Cardiac Death

2017 ◽  
Vol 40 (6) ◽  
pp. 265-271 ◽  
Author(s):  
Daniel Urcuyo ◽  
Matthew F. Blum ◽  
Qiang Liu ◽  
Ahmed Nassar ◽  
Laura D. Buccini ◽  
...  
Keyword(s):  
Vascular Resistance ◽  
Whole Blood ◽  
Cardiac Death ◽  
Ex Vivo ◽  
Donation After Cardiac Death ◽  
Donor Pool ◽  
Ex Vivo Perfusion ◽  
Perfusion Model ◽  
Renal Grafts ◽  
Kidney Perfusion

Purpose Ex vivo perfusion of marginal kidney grafts offers the chance to expand the donor pool, but there is no current clinical standard for the prolonged warm perfusion of renal grafts. This exploratory pilot study seeks to identify a stable ex vivo kidney perfusion model that can support low intravascular resistance and preserve histologic architecture in a porcine donation after cardiac death (DCD) model. Methods 15 kidneys were preserved in 1 of 3 settings: normothermic whole blood (NT-WB), normothermic Steen Solution™ (XVIVO Perfusion) with whole blood (NT-Steen/WB), or subnormothermic Steen Solution™ at 21°C (SNT-Steen). Kidneys were primarily assessed using hemodynamic parameters and histologic analysis. Results NT-WB perfusion resulted in high vascular resistance and glomerular necrosis. NT-Steen/WB and SNT-Steen resistance ranged between 0.18–0.45 mmHg/mL per minute and 0.25–0.53 mmHg/mL per minute, respectively, enabling stable perfusion for up to 24 hours. NT-Steen/WB demonstrated tubular and glomerular necrosis, while the histologic architecture of SNT-Steen was preserved with the exception of numerous proteinaceous casts. Conclusions Our results suggest that ex vivo kidney perfusion with Steen Solution™ at 21°C supports low and stable vascular resistance and provides adequate histologic preservation during 24-hour perfusion.

scholarly journals Ex Vivo Perfusion Characteristics of Donation After Cardiac Death Kidneys Predict Long-Term Graft Survival

2016 ◽  
Vol 48 (10) ◽  
pp. 3251-3260 ◽  
Author(s):  
M. Sevinc ◽  
S. Stamp ◽  
J. Ling ◽  
N. Carter ◽  
D. Talbot ◽  
...  
Keyword(s):  
Graft Survival ◽  
Cardiac Death ◽  
Ex Vivo ◽  
Donation After Cardiac Death ◽  
Ex Vivo Perfusion

Prostanoid Release from Ex Vivo Perfused Canine Arteries and Veins: Effects of Prolonged Perfusion, Intermittent Perfusion, as well as Exposure to Exogenous Arachidonic Acid, Thrombin and Bradykinin

1989 ◽  
Vol 62 (03) ◽  
pp. 1034-1039 ◽  
Author(s):  
Jan S Brunkwall ◽  
James C Stanley ◽  
Timothy F Kresowik ◽  
Linda M Graham ◽  
William E Burkel ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Ex Vivo ◽  
Fold Increase ◽  
Ex Vivo Perfusion ◽  
Cyclooxygenase Activity ◽  
Perfusion Model ◽  
Prostanoid Production ◽  
Slow Decline ◽  
Arteries And Veins ◽  
Nonpulsatile Flow

SummaryRegulation of prostanoid release from ex vivo perfused vessel segments is not fully understood. A series of perfusion experiments were performed with canine arteries and veins to define certain regulatory phenomena. Arteries were perfused with pulsatile flow of 90 ml/min at a pressure of 100 mmHg, and veins with nonpulsatile flow of 90 ml/min at a pressure of 7 mmHg. Segments were perfused with Hanks' balanced salt solution for five 15-min periods with the perfusate exchanged after each study period. With onset of perfusion, there was an initial burst of prostacyclin release to 127 ± 40 pg/mm2, declining to 32 ± 10 pg/mm2 after 60 minutes (p <0.005). If perfusion continued for 5.5 hours, there was a stable release period between 1 and 3 hours, followed by a very slow decline. At that time addition of arachidonic acid (AA) increased prostacyclin release six-fold (p <0.01). Vessels perfused for 1 hour and then rested for another hour, responded to reperfusion at the second onset of flow with a two-fold increase in prostacyclin release (p <0.01). Vessels perfused with thrombin, bradykinin or A A (either added to each perfusate or only to the last perfusate) exhibited greater prostacyclin release than did control segments. Release of thromboxane steadily declined with time in all parts of the study, and only increased with the addition of A A to the perfusate. These data indicate that vessel segments subjected to ex vivo perfusion do not maximally utilize enzyme systems responsible for prostanoid production, and after 1 hour perfusion have not depleted their phospholipids, and maintain functioning levels of phospholipase and cyclooxygenase activity. This perfusion model allows for the study of prostacyclin and thromboxane release from arteries and veins and their response to various drugs and other stimuli.

Ex Vivo Lung Evaluation of Prearrest Heparinization in Donation After Cardiac Death

2013 ◽  
Vol 257 (3) ◽  
pp. 534-541 ◽  
Author(s):  
Pablo G. Sanchez ◽  
Gregory J. Bittle ◽  
Katrina Williams ◽  
Chetan Pasrija ◽  
Kai Xu ◽  
...  
Keyword(s):  
Cardiac Death ◽  
Ex Vivo ◽  
Donation After Cardiac Death

An Ex Vivo Perfusion Model To Study the Treatment of Thrombotic Microangiopathy during Pig-to-Human Xenogenic Kidney Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3190-3190
Author(s):  
Wolf Ramackers ◽  
Lars Friedrich ◽  
Wolfgang Schüttler ◽  
Sabine Bergmann ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Histological Examination ◽  
Thrombotic Microangiopathy ◽  
Flow Resistance ◽  
Ex Vivo ◽  
Autologous Blood ◽  
Human Kidney ◽  
Pharmacological Intervention ◽  
Ex Vivo Perfusion ◽  
Perfusion Model

Abstract Early rejection of xenogenic organs is associated with thrombotic microangiopathy and changes of coagulation resembling disseminated intravascular coagulation (DIC). Here, we used an ex vivo perfusion circuit as a model of pig-to-human kidney transplantation to study the nature and treatment of this pathology. Porcine kidneys were obtained following in situ cold perfusion with HTK organ preservation solution and immediately connected to a perfusion circuit containing porcine (“autologous”) or human (“xenogenic”) AB blood supplemented with complement component C1 inhibitor (1 U/ml) and heparin (1 U/ml). Perfusion of porcine kidneys with autologous blood was feasible for >240 min in all experiments. In contrast, perfusion of porcine kidneys with xenogenic human blood was limited by a dramatic increase of flow resistance after 30 to 240 min. Increased concentrations of C3a as a marker for complement activation were associated with early perfusion failure. In addition, a dramatic increase of thrombin-antithrombin complex (TAT) and D Dimer (DD) was observed together with consumption of platelets, fibrinogen and antithrombin (AT). Histological examination demonstrated extensive thrombotic microangiopathy. Supplementation recombinant human activated protein C (rhAPC, 300 ug/l*h, n=3) or recombinant human antithrombin (rhAT, 3 U/ml, n=3) abolished the increase of flow resistance and allowed for a xenogenic kidney survival of >240 min in all experiments. Increase of DD was abolished and the consumption of fibrinogen was abrogated by both treatments as compared to control, whereas the increase of TAT was abolished only by rhAPC. Histological examination revealed no evidence of thrombotic microangiopathy for both treatments as compared to control. In conclusion, the perfusion model introduced here is a suitable tool for studying coagulopathy during early rejection in xenotransplantation. Thrombotic microangiopathy and DIC-like activation of coagulation is associated with an increased flow resistance and failure of perfusion in this model. Pharmacological intervention such as the supplementation of rhAPC or rhAT can be studied using this model and has been shown to prevent coagulopathy and thrombotic microangiopathy.

CAN WE EXPAND LIVER DONOR POOL USING DONATION AFTER CARDIAC DEATH IN THE UNITED STATES?

2010 ◽  
Vol 90 ◽  
pp. 408
Author(s):  
M. Stapfer ◽  
Y. W. Cho ◽  
L. Sher ◽  
I. V. Hutchinson ◽  
Y. Genyk
Keyword(s):  
United States ◽  
Cardiac Death ◽  
The United States ◽  
Donation After Cardiac Death ◽  
Liver Donor ◽  
Donor Pool

Oxygenated Static Preservation of Donation after Cardiac Death Liver Grafts Improves Hepatocyte Viability and Function

2015 ◽  
Vol 56 (1-2) ◽  
pp. 1-18
Author(s):  
Jiwei Yu ◽  
Masahiko Murakami ◽  
Takeshi Aoki ◽  
Bojian Jiang ◽  
Zhenghao Jin ◽  
...  
Keyword(s):  
Cardiac Death ◽  
Hepatic Function ◽  
Donation After Cardiac Death ◽  
Urea Synthesis ◽  
Sprague Dawley ◽  
Donor Pool ◽  
Cold Preservation ◽  
Uw Solution ◽  
Albumin Production ◽  
And Function

Background: Cell therapy, such as hepatocyte transplantation (HTx), is promising for the treatment of metabolic liver diseases or as a bridge to orthotopic liver transplantation in patients with fulminant liver failure. However, one of the limitations of this therapy is the shortage of donors. The present study aims to investigate whether the two-layer method (TLM) of cold preservation with oxygenation improves the viability and activity of hepatocytes from rat donation after cardiac death (DCD) donors compared with results obtained with the University of Wisconsin (UW) solution. Moreover, we evaluated the hepatocyte function after culture or transplantation into the spleen. Materials and Methods: We used male Sprague-Dawley rats for this study. The DCD model was induced by phrenotomy after injecting heparin. We assigned rats based on warm ischemia times of 15 and 30 min to groups S and L, respectively. Each group (n = 5) was then subdivided as follows: (1) group S: not preserved (S/N), preserved by TLM for 3 h (S/TLM3) and 12 h (S/TLM12), and in the UW solution for 3 h (S/UW3) and 12 h (S/UW12), and (2) group L: not preserved (L/N), preserved by TLM for 3 h (L/TLM3) and 12 h (L/TLM12), and in the UW solution for 3 h (L/UW3) and 12 h (L/UW12). The cell viability and function of isolated DCD hepatocytes were analyzed for culture or HTx into the spleen. Results: The viability and ATP levels of DCD hepatocytes significantly improved after TLM compared with the values after preservation in cold UW solution in group S/N (p < 0.059). The levels of albumin production and urea synthesis by hepatocytes after culture were significantly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12 (p < 0.05), respectively. Further, serum albumin levels after HTx were also markedly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12. The morphological features revealed that cultured and transplanted hepatocytes remained clearly viable and maintained an expression for specific hepatic function, such as the production of albumin and glycogen. Conclusion: This novel method of oxygenated cold preservation of DCD livers can expand the hepatocyte donor pool for HTx and establish a wider application of this developing technique.

scholarly journals MITOCHONDRIAL METABOLISM IS PRESERVED FOLLOWING NORMOTHERMIC EX-VIVO KIDNEY PERFUSION OF GRAFTS PROCURED FOLLOWING CARDIAC DEATH

2020 ◽  
Vol 104 (S3) ◽  
pp. S249-S249
Author(s):  
Peter Urbanellis ◽  
Caitriona McEvoy ◽  
Marko Skrtic ◽  
Ivan Linares ◽  
Dagmar Kollmann ◽  
...  
Keyword(s):  
Cardiac Death ◽  
Ex Vivo ◽  
Mitochondrial Metabolism ◽  
Kidney Perfusion
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