[Indication for the treatment of hepatic failure with baboon liver perfusion].
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Amanita↗
Biomedical subjects
T S Lie
Publications and source records attributed to T S Lie.
[Immunologic mechanism following liver transplantation. An experimental study in the rat].
To investigate the immunological status of hepatic grafts we transplanted livers from different inbred rats orthotopically on 58 LEW rats; rearterialization of the grafts was achieved with an hepatico aortal segment of the donor. Survival time depended on the donor strain; LBNF1-allografts survived in 67% (n = 12), WiS- in 60% (n = 20) and BUF- in 43% (n = 14) indefinitely. In the DA-to-LEW-combination we found no long-term survivor. Liver perfusates (LP) were prepared from 10 BDE and 10 LEW; after keeping the livers for 6 h at room temperature we perfused via portal vein with 2 ml/g Ringer's solution five times. The treatment of BDE-kidney recipients (LEW) with LP showed prolonged survival; at 5 days application 10.2 +/- 1.3 d (control: 6.5 +/- 0.5 d; P less than 0.001), at 10 days treatment 15.3 +/- 7.3 d. In vitro LP inhibited the PHA-stimulation of LEW lymphoid cells in more than 90% and the ConA-stimulation of LEW spleen cells in more than 95%. In MLC LP showed strong inhibitory effect (inhibition rate greater than 97%) even when different combinations of responding and stimulating cells were used. We assume that an unspecific immunosuppressive hepatic factor is released from ischemic damaged liver grafts which is able to prevent rejection in the induction phase. In WiS-liver recipients surviving for more than 4 months GvHR was tested after splenectomy with spleen cells. All tests showed a grade III reaction. Donor-specific skin grafts which were transplanted on these recipients survived indefinitely while third party skin grafts were regularly rejected (7.6 +/- 0.5 d). We therefore can conclude that the cellular immunosurveillance is intact, but the immunological response against donor-specific antigens is reduced. With transfer of serum from long-term-surviving WiS-liver recipients (greater than 6 months) WiS-kidney grafted LEW were able to survive also prolonged (20.7 +/- 3.4 d, control 6.2 +/- 1.0 d; P less than 0.001). Lymphoid cell transfer (1 X 10(8)) did did not result in significant prolongation of survival time (8.0 +/- 2.0 d). These observations suggest that in the steady phase specific humoral transfer factors are responsible for prolonged survival of hepatic grafts.
Animals↗
[Importance of graft arterialization in rat liver transplantation].
68 LEW-livers were grafted orthotopically into LEW; 18 with and 50 without rearterialization of the graft. 73.3% of the recipients without arterialization died of ischemic damage of the donor livers and bile ducts. The other animals survived indefinitely (more than 120 days). However, 73.3% of the recipients with graft arterialization survived more than 120 days, three animals 8-23 days. Only one recipient died of bile duct complications on the first postoperative day. These results suggest the importance of graft arterialization in rat liver transplantation, despite the observation that all untreated animals survive after complete dissection of the arterial blood flow to liver. Intraoperatively rats can tolerate acute occlusion of portal vein and vena cava inferior up to 50 min without any bypass for the decompression of splanchnic blood flow. We examined the formation of arterial collateral blood supply in the dearterialized livers by application of gelatin-medium. On day 3 we observed collateral vessels in the hilus of dearterialized livers which mainly originated from the gastroduodenal region and were connected to the remaining arterial system of the liver. Complete arterialization was shown on day 7. In the hepatic graft without arterialization the arterial collaterals were not seen until day 7, and complete arterial blood flow was demonstrated after three postoperative weeks.
Animals↗
[Possibilities and limits of temporary liver substitution by hemoperfusion with biological material].
For temporary hepatic assistance we used 200 g porcine liver pieces (5 X 5 X 5 mm3) which were perfused for 6 h with 11 swine blood. ATP and energy reserve values reached their maxima 30 min after starting perfusion, remained unchanged for 120 min, and decreased thereafter. Following 30 min of perfusion energy charge values increased from 0.260 +/- 0.110 mumol/g to 0.560 +/- 0.093 mumol/g (normal value; 0.854 +/- 0.022 mumol/g) and thereafter remained unchanged for 6 h. These results suggest that good energy regulation was maintained in the liver pieces. The small liver cubes showed excellent ammonia and phenol detoxication. However, the liver pieces were not found to be able to conjugate serum bilirubin, which might have been caused by a lack of this anatomic pathway in our model. Levels of hepatic and lytic enzymes in the perfusate increased with the time of perfusion, though they were relatively low as compared to levels in patients with acute hepatic failure. The concentration of free fatty acids in the perfusate, which are known to potentiate hepatic coma, increased slightly. However, methyl mercaptane remained constant during perfusion. Concentrations of nearly all amino acids rose during 6-h perfusion due to damage of hepatic tissues, but the molar ratio of the branched chain amino acid to aromatic amino acid was not changed. These results suggest that liberated substances from the damaged liver would not potentiate hepatic encephalopathy. We feel that hemoperfusion over small liver pieces could be a useful method for hepatic assistance.
Adenine Nucleotides↗
Comparison of a charcoal sorbent fiber with commercial charcoals for hemoperfusion.
A charcoal sorbent fiber (Enka, F.R.G.), was assessed for impurities, surface area, and adsorptive properties of its native charcoal, and compared with other uncoated activated charcoals. In vivo and in vitro hemocompatibility of the fiber were assessed as well as the adsorptive properties for endogenous toxins. The charcoal of the fiber had few impurities and a high surface area of 1,200 m2/g charcoal. For measuring the adsorptive speeds, 2 g of the uncoated charcoals were milled and screened to a particle size of 150-250 microns (Enka; 30-40 microns) and then mixed with the solutions of the individual solutes. The charcoal types of Enka, used in the charcoal sorbent fiber, and of Sutcliffe Speakman, used in the acrylic hydrogel coated charcoal, exhibited the highest adsorptive rates for bromthalein (middle molecular weight marker) and inulin (high molecular weight marker). No hematological differences among the various charcoals were found during the in vivo hemoperfusions. In the in vitro hemoperfusions with heparinized fresh blood, the fibers showed the lowest loss of leucocytes and thrombocytes. In the in vitro evaluation of the absorbents for hepatic support, the charcoal fiber and the petroleum pitch charcoal of Asahi had the best adsorptive properties for substances in the low molecular weight range.
Adsorption↗
Amino acid metabolism during hemoperfusion over biological materials.
We investigated the possibilities of liberation of toxic coma potentiating substances from the damaged hepatic tissues during the hemoperfusion over small liver pieces. Concentrations of nearly all amino acids rose during the perfusion due to the damage of hepatic tissues, but the molar ratio of BCAA to AAA was not changed. Free fatty acid levels in the perfusates increased slightly, however, methylmercaptan level remained constant. These results suggest that liberated substances from the damaged liver would not potentiate hepatic encephalopathy. Therefore, hemoperfusion over small liver pieces should be an useful method for hepatic assist because of excellent detoxification effects.
Amino Acids↗
[Liver diseases when using hormonal contraceptives (author's transl)].
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Adult↗
[Potentiation of temporary ischemic liver damage by blockage of lymph flow (author's transl)].
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Animals↗
[Immunosuppressive and cytotoxic effect of the humoral factors from ischemic damaged organs (author's transl)].
These studies demonstrate the presence of an immunosuppressive and cytotoxic factor in the perfusate of ischemic damaged liver. A BDE rat liver perfusate (LP) was prepared after 6 h warm ischemia by intraportal perfusion with 2 ml/g of Ringer's solution (one time-LP1 or five times-LP5 with the same volume of solution). Protein amount of LP1 and LP5 was 0.9 and 2.8-3.9 mg/ml. In vivo activity of the hepatic perfusates was studied by effect on renal allograft survival time. LEW rats with BDE kidney transplant, treated daily with 2 ml of LP1 for 5 days, starting on the day of grafting, survived 8.9 +/- 1.8 days, significantly longer than control animals (6.5 +/- 0.5 days). After administration of LP5 renal recipients survived 10.3 +/- 1.3 days and when the treatment with LP5 was prolonged to 10 days animals survived 9-34 days (mean 15.3 +/- 7.3 days). The presence of the suppressive factor was also studied in renal, spleen and heart extracts, prepared after 6 h warm ischemia. Protein amount of extracts was adjusted to 3-4 mg/ml by Ringer's solution. Immunosuppressive activity of LP and other organ extracts was tested in vitro by their influence on MLC reaction (LEW and BDE lymphocytes) and on LEW cells in the PHA stimulation assay. Lymphocyte blastogenic response on MLC reaction and in culture with PHA was strongly inhibited by LP but weakly by organ extracts. Hepatic perfusates were cytotoxic against lymphocytes and fibroblasts in a three day cultures. Cytotoxic activity of the organ extracts was lower than LP. Extract of the cold preserved kidneys showed immunosuppressive and cytotoxic effect like extract of ischemically injured kidneys but smaller than LP. After heat inactivation at 70 degrees C the activity of hepatic perfusate decreased. Immunosuppressive organ factor (IOF) seems to be a normal cell component, not a decomposition product of the ischemically damaged hepatic tissue.
Animals↗
Treatment of acute hepatic failure by hemoperfusion over baboon and human livers: alphafetoprotein levels in serum.
Twelve patients with acute liver failure, two patients with cirrhotic failure of the liver, and one patient in the terminal stage of cirrhotic liver were treated. The patients had grade IV or V hepatic coma. Twenty-seven perfusions were carried out, each lasting 8 to 27 hours, with one to four perfusions per patient. Eight patients with acute liver failure were brought out of the coma. Six of them showed sufficient clinical symptoms of hepatic regeneration; five of these could be discharged. These results suggest that 50% of complete clinical recovery of consciousness from grade IV or V coma in acute hepatic failure is possible with this therapy. The three patients with liver cirrhosis treated with a total of five hemoperfusions did awaken, but died because of insufficient hepatic regeneration. The serum alphafetoprotein (AFP) levels were examined. In those patients brought out of the coma, a rapid increase of AFP up to 260--500 ng/ml was observed. These levels remained high for several weeks in the patients who survived. In the patients who died of liver insufficiency, AFP levels increased only slightly or briefly, so AFP could be a good criterion for determining the prognosis for coma patients with this treatment.
Adult↗
[Serum concentrations of alpha 1-fetoprotein in acute hepatic failure treated by hemoperfusion with baboon livers (author's transl)].
9 patients with acute hepatic necrosis following virus hepatitis or hepatic intoxication and 2 patients with acute necrosis of cirrhotic liver, all with stage IV or V hepatic coma, were treated by hemoperfusions with baboon livers. Serum levels of alpha 1-fetoprotein (AFP) were examined prae-, intra- and post perfusion by radioimmunoassay. In 4 patients who survived, the AFP-levels increased from 20 to 65 ng/ml to 180 to 480 ng/ml and remained raised for more than one week. In the patients who died of liver insufficiency, the AFP-levels were only slightly or temporarily increased. The alpha 1-fetoprotein determination is a reliable criterium for the prognosis of hepatic coma patients treated by hemoperfusion.
Adult↗
[A humoral transfer factor preventing rejection of allotransplanted rat liver? (author's transl)].
We grafted orthotopically 11 DA and 20 WiS-livers into LEW. The recipients of DA-livers survived 10.5 +/- 4.3 days; of the 20 recipients of WiS-liver, however, nine survived 18-37 days, and the other 11 survived indefinitely. The cells of recipients who survived more than 4 months showed GvHR of grade III, and their transfer showed no significant immunosuppressive effect. The indefinitely surviving liver recipients could accept specific skin grafts, but normally rejected third party skin. The serum of these recipients was able to prolong the survival of kidney grafts. This transfer factor is in our estimation responsible for the prolonged survival of rats with liver grafts.
Animals↗
Suppression of cell-mediated immunity in rats transplanted with kidneys from donors compatible at the major histocompatibility complex.
In order to study the immunological status of rats transplanted with H-1-compatible kidney allografts, LEW rats were grafted with F and (Fischer X Lewis)F1 (FLEWF1) kidneys. Most of the F kidneys were rejected within 55 days, only 4 of 24 surviving for more than 4 months. However, two-thirds of the FLEWF1 recipients survived for more than 4 months, the others having died within 64 days. During the first postoperative week, high levels of serum lymphocytotoxic antibodies were found in recipients of F kidneys, and thereafter there was little change. In this respect these rats did not differ from recipients of kidneys with major histocompatibility differences. However, recipients of FLEWF1 kidneys had low haemagglutinating and lymphocytotoxic antibody titres. No serum-blocking factor could be found in kidney of recipients by use of the microcytotoxicity assay (MCA) or inhibition of allorosette formation. Cellular immunity, which was studied by means of the graft-versus-host reaction (GVHR) and the microcytotoxicity assay, was detected in the first postoperative week. This immunity gradually declined, and after 6 weeks it was no longer detectable. The immunological status of the long-term surviving kidney recipients remained unchanged, even when they were provided with further antigenic challenge in the form of two successive donor strain skin grafts.
Animals↗
Problems of competition in charcoal hemoperfusion for the treatment of intoxications.
Both toxic and physiological substances are adsorbed during an extracorporeal hemoperfusion for the treatment of exogenous and endogenous intoxications. Using a closed circuit in vitro, we perfused one liter saline or fresh human plasma with 4425 mumol creatinine, 4854 mumol and 97,086 mumol barbital-Na, 597 mumol bromthalein, 1942 mumol and 29,126 mumol raffinose, and 200 mumol inulin in different combinations over 70 gm of uncoated charcoal with the following results: 1. The adsorptive capacity of other substances is not influenced by preadsorption of the charcoal with a low or middle molecular weight substance; 2. In the low and middle molecular weight range, there is no competition between two substances in a solution; 3. The simultaneous usage of two substances of middle and high molecular weight, or preadsorption with a high molecular weight substance, reduces the rate of adsorption and the capacity of charcoal for middle molecular weight substances, but not for low molecular weight substances.
Adsorption↗
[Possibilities to avoid adsorption of physiological substances during charcoal hemoperfusion (author's transl)].
For the clinical use of charcoal in intoxications the loss of normal substances out of the organism must be avoided. In order to study the possibility of pretreating the charcoal with certain substances without influencing the adsorptive capacity of toxic metabolic products we perfused over 70 g uncoated charcoal for 6 h: 500 mg creatinine, 1 g and 20 g barbital, 500 mg bromthalein, 1 g raffinose resp. 1 g inulin per litre physiological saline in different combinations and found the following results: 1. In low and middle molecular weight levels there is no competition between two substances. 2. By preadsorption of the charcoal with a low or middle molecular weight substance, the adsorptive capacity of other substances is not influenced.
Absorption↗
[Extracoporeal vital liver perfusion in the treatment of acute hepatic coma].
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Acute Disease↗
Active enhancement of canine liver allografts with polyspecific antigen.
Of 34 canine liver allograft recipients, 17 in the control group survived for 6.9 +/- 1.5 days. Six recipients, group 3, were given 780 milligrams per kilogram of body weight polyspecific semisoluble antigen prepared from 20 spleens together with 10 milligrams per kilogram of body weigth prednisolone on days 15, 8 and 1 before transplantation. The mean survival time of this group was 10.1 +/- 2.0 days, p less than 0.01, compared with the control group. Six other recipients, group 4, were similarly treated with antigen from a pool of 70 spleens. Three survived for more than three weeks, and the other three died on days 1, 7 and 8 postoperatively with signs of accelerated rejection. Donors and recipients were not identical for leukocyte defined determinants. The recipients displaying accelerated rejection had markedly higher lymphocytotoxic and hemagglutinating antibodies. In addition, all recipients undergoing progressive rejection showed an inhibition of leukocyte migration. After three antigen dosages, rosette forming lymphocytes were present in increased numbers in peripheral blood and remained unchanged thereafter.
Animals↗
[Extracorporeal perfusion with baboon liver in the treatment of hepatic coma (author's transl)].
In 11 patients with hepatic coma (stage IV and V according to Abouna) extracorporeal haemoperfusion using the Scribner shunt (radial or profunda femoris artery) was performed over 12 to 27 hours with 22 baboon and one human livers. Eight patients emerged from coma, six of them showed sufficient regeneration of the diseased liver. Four patients were discharged as cured, one patient died of acute pancreatic necrosis, a further one due to bleeding from an old gastric ulcer. In the 2 remaining patients the coma recurred within 48 hours. Tree patients never came round from coma. After perfusion no antibodies against baboon proteins were demonstrable in the patients. Thus there is very little danger of an anaphylactic reaction when perfusion is repeated. The titre of preformed cytotoxic antibodies against baboon cells in patients' serum rises only after 1-2 weeks and decreases again after 4 weeks. In our experience extracorporeal liver perfusion with baboon or human livers is the most promising method for treatment of hepatic coma.
Adult↗