PUMA
Istituto di Fisiologia Clinica     
Boggi U., Bellini R., Vistoli F., Capellini S., Kusmic C., Campani D., Barbieri U., Sartucci F., Burchielli S., Trivella M. G., Filipponi F., Mosca F. Technical problems with a model of ex vivo liver perfusion in the pig. In: Transplantation Proceedings, vol. 32 (08) pp. 2726 - 2729. elsevier, 2000.
 
 
Abstract
(English)
A SYSTEM capable of efficiently supporting patients in fulminant hepatic failure (FHF) until either recovery (bridge to regeneration) or until liver transplantation (bridge to transplantation) would be very much needed. Recent research efforts have mainly focused on the development of different types of bioreactors using porcine hepatocytes as living components.1,2 The main difficulty limiting the development of these devices is the fact that the complexity of metabolic and synthetic functions of the liver is difficult to reproduce in an artificial model. Indeed, whereas most vital organs perform clearly defined biological or mechanical functions, the liver is a biochemical reactor whose full range has not yet been completely defined. Mechanical devices, such as hemodyalisis,3 plasmapheresis, 4 hemofiltration,5 or charcoal6,7 and resin hemoperfusion, 8 cannot completely replace liver functions, and it is becoming increasingly evident that the effective liver assistance requires a biologically active device. However, as long as living components (potential biohazard) are required, the same result can be obtained using a whole liver instead of a biologically active reactor designed to reproduce liver functions. A method of extracorporeal liver perfusion to support patients in FHF was reported as early as 1968 by Abouna9-11 and recently refined in a preclinical trial.12 However, despite the description of several successful liver perfusions,13-15 the system has not gained widespread popularity. If, on one hand, the concurrent development and continuously growing success of liver transplantation has limited the clinical application of ex vivo liver perfusion, then on the other hand the investigators who have attempted these perfusions have not been able to duplicate Abouna's results.16 More importantly, criteria for ex vivo viability, impaired by perfusion with human blood, were never established17 and thrombocytopenia led to severe bleeding complications.16 Nowadays, in view of the possible availability of transgenic livers as well as of other systems capable of reducing or circumventing the harmful effects of xenogeneic disparities, it appears legitimate at least to verify the technical feasibility of ex vivo liver perfusion in a large animal model of FHF. The main aim of this study was to evaluate the technical and physiopathological problems of a model of ex vivo liver perfusion in the pig. Additionally, the efficacy of the system, in terms of possibility of prolonging survival and correcting biochemical and neurological disturbances of FHF, was determined by recording its effects on a standardized model of total hepatectomy.18 MATERIALS AND METHODS An anhepatic model of FHF was created in 28 pigs weighing between 29 and 51 kg (mean weight, 40.4 kg). The following parameters were measured before hepatectomy and every 2 hours thereafter until death: hemoglobin, hematocrit, number of red blood cells, core body temperature, mean arterial pressure, serum creatinine, coagulation (prothrombin time, fibrinogen, platelet count, factor V, factor VII), urinary output, electrocardiogram, direct blood pressure, heart rate, and electroencephalographic activity according to the Huguet scale.19 Maintenance of homeostasis in the perfused organs was verified, at the same intervals, by recording: perfusion flows and pressures, temperature, bile production, and oxygen consumption. Three pigs died early after hepatectomy. Seven animals, used as controls, were monitored serially until brain death without liver support. The remaining 18 pigs underwent different techniques of extracorporeal liver perfusion. Starting from Abouna's circuitry and technique, the system was progressively modified to overcome the problems encountered. Similarly, both timing and duration of perfusion were modified to verify the effect on animal survival. Medical support was identical in control and treated animals and consisted of continuous infusion of 10% dextrose solution (to maintain blood glucose levels between 75 and 100 mg/dL) and correction of electrolyte and acid-base balances as required.
URL: http://scienceserver.cilea.it/cgi-bin/sciserv.pl?collection=journals&journal=00411345&issue=v32i0008&article=2726_tpwamovlpitp&form=pdf&file=file.pdf
Subject liver perfusion
ex vivo


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