Hypothermic machine perfusion of liver grafts for transplantation: technical development in human discard and miniature swine models.
BACKGROUND
Cold storage (CS) is the standard preservation technique for liver transplantation (LTx). Hypothermic machine perfusion (HMP) is an alternative preservation technique that provides a continuous supply of substrates and removes waste products. HMP improves early graft function in kidney transplantation, especially for marginal organs: To our knowledge there have been no reports HMP in human LTx. The aim of this study was to develop a reproducible technique for liver HMP prior to initiating a clinical trial.


METHODS
For the discard protocol, between May 2001 and March 2002, 10 nontransplantable human livers were obtained. We designed a model of atraumatic, centrifugal HMP of the portal vein (PV) and hepatic artery (HA) via donor vascular conduit. Livers were perfused at 3 degrees C to 5 degrees C with Vasosol solution for 5 to 10 hours using a modified Medtronic Portable Bypass System. Perfusion variables (temp, flow, pressure) where recorded every 30 minutes. During the study, we also validated our techniques in an animal model. For the animal protocol; six swine were used as liver donors and randomized to 12 hours of CS in UW (n = 3) or 12 hours of HMP using Vasosol solution (n = 3). LTx was performed in six swine. Animals survived until postoperative day 5.


RESULTS
For the discard protocol, mean HMP time was 6.7 +/- 1.8 hours. Target flow was 0.7 mL/g liver/min. PV and HA pressure ranged from 3 to 5 and 12 to 18 mm Hg, respectively. All grafts were maintained at 3 degrees C to 5 degrees C during HMP. For the animal protocol, all recipients had good liver function and survived to postoperative day 5. AST and TBili were similar between CS and HMP.


CONCLUSIONS
Our method of liver HMP appears to be a safe and reliable method to preserve livers. A clinical trial is now underway to evaluate this technique in human LTx.
Guarrera
J V
JV
Department of Surgery, New York Presbyterian Hospital, New York, New York 10032, USA. jjg46@columbia.edu
Estevez
J
J
Boykin
J
J
Boyce
R
R
Rashid
J
J
Sun
S
S
Arrington
B
B
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D004187:Disaccharides; D004573:Electrolytes; D005971:Glutamates; D005978:Glutathione; D006639:Histidine; D006801:Humans; D007036:Hypothermia, Induced; D007328:Insulin; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000379:methods* / Q000502:physiology; D008353:Mannitol; D023421:Models, Animal; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D011887:Raffinose; D013552:Swine; D013556:Swine, Miniature
C088453:Celsior; D004187:Disaccharides; D004573:Electrolytes; D005971:Glutamates; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D008353:Mannitol; D006639:Histidine; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose