Devascularization Surgical Model of Acute Liver Failure in Minipigs

Abstract

Aim: The study was designed to develop a readily reproducible model of acute liver failure (ALF) in the minipig, to gain an 8-hour therapeutic window to mimic, as closely as possible, acute liver failure in man. Method: We used reversible devascularization model of ALF in the minipig involving hepatic artery ligation and establish an end-to-side portocaval anastomosis. Standard laboratory monitoring was complemented with intracranial pressure (ICP) measurement. Material: Twenty minipigs (weight 25–30 kg) were used for the experiment. The animals were divided into 3 groups: I: 10 animals in an experimental group with ALF; II: 5 animals in an experimental group with ALF and ICP measurement, and III: 5 animals in a control group without ALF. Results: Laboratory testing has shown the significant changes in levels of AST (33.44 ± 39.96 vs. 1.56 ± 0.50 mmol/l), lactate (2.97 ± 1.16 vs. 1.18 ± 0.61 mmol/l), and ammonia (264.3 ± 93.05 vs. 42.5 ± 12.98 mmol/l) between ALF groups and controls (p < 001) 6 h after the operative procedure, and significant changes in hypoglycemia and intracranial pressure were found 4 h after the operative procedure. The difference in Quick values (67.4 ± 17.03 vs. 75.2 ± 2.68) was not significant. We assume that the therapeutic window starts 4 h after the beginning of the experiment. Conclusion: Our devascularization model of ALF is simple and readily reproducible. The therapeutic window occurring shortly after surgery and persisting for a mean 9 h is suitable to evaluate bioartificial liver devices.

Evaluation of Liver Support Systems for Preclinical Testing by Animal Trials

“…This is a consequence not only of differences in ethical guidelines and philosophy regarding husbandry, but also of the large difference in the mode of the application of the different LSS. A number of interrelated considerations, some of which remain unclear or controversial, are involved here, including: (i) allow natural course (49,64,65); (ii) maintain or stop anesthesia/sedation; (iii) allow free movement; (iv) provide full clinical intensive care (10); (v) blood products (66-68); (vi) apply hypothermia (69); (vii) mode and content of nutrition (70)(71)(72); (viii) prophylactic drugs (49); and (ix) which (3,5,6,13,54,55) I, V G, H (49,50), I Ischemia reperfusion (3) I, II, III, …”

“…Meanwhile, the investigator should not underestimate the survival time differences of, for example, pigs following total hepatectomy. However, the relatively short survival time and rapid decline in test subjects (49,50) can produce practical difficulties for some studies, for example, when the investigator's aim is to show the effects of LSS on the long-term physiological functions' stabilization or improvement. It could be an advantage for another study, especially for the preclinical testing of LSS intended for BtT, as well as it could be less lasting for animals and more costeffective.…”

A simple dummy liver assist device prolongs anhepatic survival in a porcine model of total hepatectomy by slight hypothermia

“…Animal models of ALF are mainly based on surgical techniques such as devascularisation [8], ischemia [9], extensive/total liver resection [10,11] or medical interventions such as hepatic intoxication with acetaminophen [12], amanitin [13] or galactosamine [14]. Unfortunately all aforementioned models involve various limitations, thus affecting morbidity in the assessment of a given intervention.…”

A New Surgical Model for Hepatectomy in Pigs

“…Hepatic failure can be caused by intoxication with various hepatotoxic drugs like acetaminophen [3] , carbotetrachloride [4,5] , galactosamine [6,7] and dimethylnitrosamine [8] . Infectious models using viral agents [9] , heat-killed bacteria or lipopolysacharides [10] and surgical attempts like ischemia models with total devascularization by ligation of the hepatic artery and portocaval shunting or temporary clamping of the vessels are described [11][12][13] . Various models for extended resection of the liver [14] exist.…”