Furukawa, H

Imventarza, O

Miyata, T

Starzl, TE

Todo, S

Ueda, Y

PubMed

Name not available

Endogenous endotoxemia during orthotopic liver transplantation in dogs

D-Scholarship@Pitt

Endogenous Endotoxemia During Orthotopic Liver Transplantation in Dogs T. Miyata, S. Todo, O. Imventarza, Y. Ueda, H. Furukawa, and T.E. Starzl AL THOUGH the I-year survival rate after clinical orthotopic liver transplantation (OL TX) has been improved to about 70%,' 15% of the patients still die within the first month as a result of complications. such as shock, multiple organ failure, and bleeding. Although various fac-tors have been found to be involved in these postoperative complications, the overall mechanism has not been well elucidated. The liver normally contributes more than 80% of the blood cleaning functions of the reticuloendothelial system.2 During OL TX, this hepatic contribution temporarily is lost (anhe-patic phase), and toxic substances including endotoxin can flood the circulation. To our knowledge, there has been no report concerning endotoxemia during OL TX. Endotoxin is a cell wall component of gram-negative bacteria and has lipid A as the central component in its structure. Endotoxin triggers shock,3 pulmonary failure,4 and disseminated intravascular coagulation. 5 It is absorbed from the intestine even under conditions of health. 6 Recently, a highly sensitive quantitative method has been developed for plasma endotoxin determination using chromogenic sub-strate and perchloric acid. 7 MATERIALS AND METHODS We used a modification of this method' to determine whether endoLOxemia occurred at the time of OLTX in dogs. Briefly, dogs' platelet poor plasma was added to perchloric acid, and the neutral-ized supernatant from this mixture was incubated with Japanese horseshoe crab Tachyplcustridentatus and a chromogenic substrate (Seikagaku Kogyo, Tokyo). The absorbance was measured at 545 nm after diazotization. All procedures before diazotization were (Q E (/) C1l a:: c c )( o o (pg/ ml) 200 150 100 "0 50 c w end of.J' an hepatic 3hr stage GroupA en = 9) 12hr 24hr 3days 7days Fig 1. Change of peripheral blood endotoxin levels in dogs not given neomycin preoperatively (group A). (pg/ ml) 200 co E 150 C/) (Q a:: .!: 100 c 'x 0 .... 0 -C 50 c w Group B (n = 7) o~K~~~~~~~~~~~-end ofJ-anhepatic stage 3hr 12hr 24hr 3days 7days Fig 2. Change of peripheral blood endotoxin levels in neomy-cin-treated dogs (group B). carried out in a pyrogen-free manner. As a reference, endotoxin 0111 B4 was used. Student's t-test was used for the comparison of endotoxin values, and the X' test was employed for the comparison of mortality. Sixteen healthy beagle female recipients weighing 10-15 kg underwent OLTX from mongrel donors of either sex. The experi-ments were divided into two groups. In group A (n = 9). no antibiotic treatment was given before the OL TX, whereas in group B (n = 7), 750 mg neomycin was given by mouth 3 times/day for 3 days, All the operations were performed by the same team, using a standard technique! The livers were infused and preserved with chilled lactated Ringer's solution and had cold ischemia times of 25-40 minutes before portal revascularization. Beginning on the morning after transplantation, the dogs were treated orally with 20 mg/kg/day CyA. which was dissolved in ethanol and in olive oil to a concentration of 100 mg/ml of solution. Samples for endotoxin measurement were drawn from a periph-eral vein, collecting 3 ml in a pyrogen-free disposable syringe. The blood was anticoagulated with 10 units heparin/ml sample. Sam-pling was immediately before liver grafting, at the end of the anhepatic phase, 3, 12. and 24 hours after the end of the anhepatic phase, and 3 and 7 days after the operation if the dog lived this long. From the Department of Surgery. University of Pittsburgh School of Medicine, and the Veterans Administration Medical Center, Pittsburgh. Pennsylvania. Supported by Research Grants from the Veterans Administra-tion and Project Grant No. DK·29961 from the National Institutes of Health, Bethesda. Maryland. Address reprint requests to Thomas E. Starzl. MD. PhD, Falk Clinic, 3601 Fifth Avenue. Pittsburgh. PA 15213. © 1989 by Appleton & Lange 0041-1345/89/$3.001 +0 Transplantation Proceedings, Vol 21. No 5 (October). 1989: pp 3861-3862 3861 ------- ---------------------------------------------------------3862 The sample was immediately centrifuged at 3000 rpm for 10 minutes and stored at - 80°C until the analysis. RESULTS Before OL TX, the endotoxin levels in the peripheral blood «5 pg/ ml) did not differ between group A and group B. During the anhepatic phase, the maximum endotoxin levels in group A increased to 128.1 ± 20.6 pg/ml (Fig 1) and in group B to 59.0 ± 15.5 pg/ml (Fig 2). The difference between groups was significant (p < 0.01). This endotox-emia lasted for more than 12 hours after the end of the anhepatic phase. Seven of the 9 dogs not given neomycin (group A) died within 14 days of pulmonary failure (5), bleeding (4), and lymphatic ascites (1); 3 of these animals had more than one principal cause of death. The periopera-tive endotoxemia tended to be greater in the animals that did not survive through the 2-week observation period (Figs I, 2). Two of the 7 dogs given neomycin (group B) died within 14 days, both from intestinal intussusception. The difference between the groups in 2-week mortality was significant (p < 0.05). MIYATA, TODO, IMVENTARZA ET AL CONCLUSIONS These data suggest that endogenous endotoxemia occurring during OL TX may play an important role in the develop-ment of complications after OL TX. Endotoxin currently is being measured during and after OLTX in humans. REFERENCES I. Starzl TE, Demetris AJ, Van Thiel D: N Engl J Med (in press) 2. Green R, Wiznitzer T, Rutenburg S, et al: Proc Soc Exp Bioi Med 108:261, 1961 3. Balis JA, Rappaport ES, Gerber L, et al: Lab Invest 38:511, 1978 4. Miyata T, Torisu M: Jpn J Surg 16:412, 1986 5. Robbins SL, Angell M: Basic Pathology, 2nd ed. Philadelphia: W.B. Saunders Co., 1976:363 6. Jacob AI, Goldberg PK, Bloom N, et al: Gastroenterology 72: 1268, 1977 7. Tamura H, Obayashi T, Takagi K, et al: Thromb Res 27:51, 1982 8. Ikeda T, Hirata K, Tabuehi K, et al: Cire Shock 23:263,1987 9. Todo S, Porter KA, Kam I, et al: Transplantation 41 :296, 1986 

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Endogenous endotoxemia during orthotopic liver transplantation in dogs

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