H. Lang et al., Isolated hyperthermic liver perfusion with high dose tumor necrosis factoralpha in pigs: An experimental study in preparation of clinical use, EUR SURG RE, 32(1), 2000, pp. 1-10
Isolated hyperthermic perfusion of the liver was performed for 45 min in 27
pigs via hepatic artery and portal vein at mean inflow temperatures betwee
n 40.7 and 41.2 degrees C, In two study groups B and C (n = 9 pigs each) 50
mu g recombinant human tumor necrosis factor-alpha (rhTNF alpha) per kg bo
dy weight were added to the perfusate, whereas in a control group A liver p
erfusion was done without rhTNF alpha, Before reperfusion the livers were w
ashed out with Ringer's solution in all groups followed by a protein soluti
on in group C. At 30 and 60 min after reperfusion the maximum systemic rhTN
F alpha concentrations were significantly higher in group B with 68 and 61
ng/ml compared to 14.5 and 14.9 ng/ml in group C (p < 0.05). Mean systemic
porcine TNF alpha concentration was significantly higher in group B (217 pg
/ml) compared to group C (50 pg/ml) 30 min after reperfusion (p = 0.012). S
urvival was 7/9 in group A and C and only 2/9 in group B with 6/7 pigs dyin
g due to severe cardiopulmonary failure within 12 h after operation. In sur
viving pigs of group A and C only mild and transient hepatotoxicity was reg
istered, The presented study underlines the feasibility of high dose rhTNF
alpha application in an isolated hyperthermic liver perfusion system. Washo
ut of the liver with a protein solution before reperfusion reduces systemic
TNF alpha levels as well as associated lethal cardiocirculatory and hepato
toxic side effects. Copyright (C) 2000 S. Karger AG, Basel.