Isolated hyperthermic liver perfusion with high dose tumor necrosis factor alpha in pigs: an experimental study in preparation of clinical Use.
Isolated hyperthermic perfusion of the liver was performed for 45 min in 27 pigs via hepatic artery and portal vein at mean inflow temperatures between 40.7 and 41.2 degrees C. In two study groups B and C (n = 9 pigs each) 50 microg recombinant human tumor necrosis factor-alpha (rhTNFalpha) per kg body weight were added to the perfusate, whereas in a control group A liver perfusion was done without rhTNFalpha. Before reperfusion the livers were washed out with Ringer's solution in all groups followed by a protein solution in group C. At 30 and 60 min after reperfusion the maximum systemic rhTNFalpha 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 TNFalpha concentration was significantly higher in group B (217 pg/ml) compared to group C (50 pg/ml) 30 min after reperfusion (p = 0.012). Survival was 7/9 in group A and C and only 2/9 in group B with 6/7 pigs dying due to severe cardiopulmonary failure within 12 h after operation. In surviving pigs of group A and C only mild and transient hepatotoxicity was registered. The presented study underlines the feasibility of high dose rhTNFalpha application in an isolated hyperthermic liver perfusion system. Washout of the liver with a protein solution before reperfusion reduces systemic TNFalpha levels as well as associated lethal cardiocirculatory and hepatotoxic side effects.
Lang
H
H
Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Deutschland.
Thyen
A
A
Nadalin
S
S
Frerker
M
M
Moreno
L
L
Flemming
P
P
Martin
M
M
Oldhafer
K J
KJ
Raab
R
R
D000818:Animals; D010478:Chemotherapy, Cancer, Regional Perfusion; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008099:Liver / Q000187:drug effects*; D008854:Microscopy, Electron; D011994:Recombinant Proteins / Q000008:administration & dosage; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha