JOURNAL
OF SURGICAL
Gastric
RESEARCH
25, 496-500
(1978)
Ulceration Complicating Pig Liver Transplantation: Protective Effects of Gastroenterostomy or Highly Selective Vagotomyl
The
ROSEMARY VAN HOORN-HICKMAN, CH.M., W. A. VAN HooRN,M,B.CH.B., ANDJOHNTERBLANCHE,CH.M. Department
of Surgery & Medical Research Council Liver Research Group, Groote Schuur Hospital, Cape Town, South Africa Submitted
for publication
June 23, 1977
Gastric ulceration frequently complicates liver transplantation as well as other operations in pigs. These animals usually die of fatal hemorrhage within 10 days. The prevention of this complication by gastroenterostomy or highly selective vagotomy was studied in groups of transplanted pigs with or without splenectomy, and also in those with bile duct ligation. Gastroenterostomy reduced the incidence of ulceration associated with liver transplantation to 27%. whereas highly selective vagotomy (HSV) almost totally abolished ulceration. Animals with HSV and the spleen left in situ showed the long survival anticipated in the pig with indolent biochemical changes suggestive of lowgrade rejection. Thus animals could be studied for much longer periods and HSV should be considered as an adjunct to any procedure which is complicated by a high incidence ofgastric ulceration and hemorrhage.
The pig is notorious for its susceptibility to gastric ulceration both spontaneously [ 151 and in association with surgical procedures, especially liver transplantation 16, 121. The development of jaundice during rejection simulates the obstruction which results from bile duct ligation-a procedure known to result in ulceration in 100% of cases and in fatal gastrointestinal hemorrhage in 60% [ 11. Previous studies had suggested that gastroenterostomy might be protective [ 161but that neither the administration of cimetidine (Castles, unpublished observations) nor of intravenous gastrin [19] were protective. Highly selective vagotomy had been show to prevent ulceration in bile duct ligated pigs [20]. This study compares the use of gastroenterostomy or highly selective vagotomy in an attempt to prevent gastric ulceration in pigs after liver transplantation. The standard technique of liver r Reprint requests should be addressed to Dr. R. van Hoom-Hickman, Department of Surgery, Medical School, Observatory 7925, South Africa. 00224804/78/025(r04%$0
1.00/O
Copyright 0 1978 by Academic Press, Inc. All rights of reproduction in any form ressrved.
496
transplantation in this laboratory included splenectomy after use of the splenic vein for portosystemic bypass [7], but in order to exclude the role of gastric devascularisation following highly selective vagotomy plus liver transplant with splenectomy, the spleen was removed in some transplants and not in others. MATERIALS
AND METHODS
The pigs used were 6- to 8-week-old nonlitter-mates of Large White X Landrace breed, weighing 20 to 25 kg. After a 24 hr period of starvation, anesthesia was induced with thiopentone sodium (2-3 mgfkg) and was maintained with nitrous oxide and oxygen using a Magill-type circuit and intermittent positive pressure ventilation. Liver transplantation was performed by the standard techniques of this laboratory [9]. When the spleen was to be removed, the portosystemic bypass necessary for splanchnic decompression during the transplant was taken from the splenic vein to the jugular
HOORN-HICKMAN
ET AL.: PIG LIVER
TRANSPLANTATION-ULCER
vein, with subsequent splenectomy. When the spleen was left in situ, the bypass was inserted into the recipient portal vein and was removed just before the portal anastomosis was begun. Highly selective vagotomy (HSV) was performed as previously described [14, 211 being a modification of the method in humans of Johnston and Wilkinson [ 111.Particular care was taken to avoid the third pleural space which surrounds the oesophagus in the pig [ 151.
497
Postoperatively, animals received 2 liters of 10% invert sugar in Ringer’s lactate intravenously for 2 days with chloromycetin and penicillin (1 g each) daily for 5 days. Blood samples were taken daily for measurement of alkaline phosphatase, bilirubin, and aspartate aminotransferase as previously described [ 111. Autopsy was done as soon as possible after death. The animals were studied in the following groups:
1. Liver transplant + HSV (a) + splenectomy (b) - splenectomy 2. Liver transplant - HSV (a) + splenectomy (b) - splenectomy 3. Liver transplant (a) - gastroenterostomy (b) + gastroenterostomy 4. Bile duct ligation + gastroenterostomy RESULTS
PREVENTION
11 11 with splenectomy 6
group without splenectomy (2b), the mean ulcer incidence was 66% and the survival 16 -+ 8 days. The only two animals which did not develop ulcers showed no evidence of rejection and survived more than 21 days. In all animals which rejected comparison of the incidence of ulceration in those treated by highly selective vagotomy as compared with those not treated by HSV showed a total incidence of 33% with HSV and 100% without HSV (P > 0.05 using McNemar’s test). In a separate series of experiments gastroenterostomy had no effect on the ulcers which developed after bile duct ligation (group 4). In the animals with liver transplants the incidence of ulceration was 48% without gastroenterostomy (3a) and 27% when gastroenterostomy was added (3b). In groups 3b and 4 intestinal obstruction was noted in 2 of 11 and 2 of 6 pigs, respectively.
Incidence of ulceration and other causes of death (Table 1). The pars esophageal ulceration which occurred in these pigs was identical to that classically described [ 1, 31, viz., total denudation of the pars esophageal mucosa with massive intragastric hemorrhage. Animals in which highly selective vagotomy (HSV) was performed in addition to liver transplantation, showed a lower incidence of ulcers than those without HSV. In the HSV group with splenectomy (la) the ulcer incidence was 43% and the survival time 13 ? 4 days. In the HSV group without splenectomy (lb), the ulcer incidence was 20% and the mean survival was 35 2 10 days. Only one animal developed an ulcer which occurred in the 9th postoperative week; postmortem showed the unusual complication of bile duct stricture. Biochemistry In contrast when no highly selective vagotIn groups 1 and 2, there was no significant omy was done, 100% of the group with splenectomy (2a) developed ulcers with fatal difference in the biochemical changes hemorrhage and death at 9 +- 2 days. In the studied whether the spleen was removed or
498
JOURNAL OF SURGICAL RESEARCH: VOL. 25, NO. 6, DECEMBER 1978 TABLE 1 SURVIVAL
AND CAUSES OF DEATH
No.
Survival (days, mean 2 SE)
Percentage ulceration
I. Transplant + HSV (a) with splenectomy (b) without splenectomy
7 5
132 4 35 + 10
43 20
2. Transplant-HSV (a) with splenectomy (b) without splenectomy
6 6
9k 16-t
2 8
loo 0 in 2 lOttin
3. Transplant (a) - gastroenterostomy (b) + gastroenterostomy
4. Bile duct ligation + gastroenterostomy
11 11
ll+ 125
6 9
48 21
6
12
2
100
left intact, hence the data from each group were combined. In group 3 gastroenterostomy did not affect the biochemical changes and results are considered as one group. The levels of AAT, alkaline phosphatase, and bilirubin in the three groups of transplants were similar, showing increases from the 4th or Sth day. In the longer survivors of group 1, these iiver function tests showed intermittent fluctuations above normal. Animals with bile duct ligation showed progressive increase in bilirubin and alkaline phosphatase but no evidence of hepatocyte damage,
Other causes of death
2 pneumonia; 2 rejection 3 pneumonia; 1 sepsis
Nil Pneumonia without evidence of rejection Rejection 3 pneumonia; 3 rejection 2 pneumonia; 2 rejection 2 intestinal obstruction
2 intestinal obstruction
tion. The variable rejection response of the pig to liver transplantation [2, lo] has resulted in differing incidences of gastric ulceration. Each factor was found to contribute to ulceration, with a high incidence associated with rejection. In laboratories where the incidence of rejection is high 12, 81, gastric ulceration severely interferes with any sustained studies as animals die too early to be useful [5]. Calne et af. [4] have reported that truncal vagotomy prevents ulceration but this technique is difficult in the pig [14] and not widely used. Vagotomy and pyloroplasty has also been used with only limited success [12]. Cimetidine (Castles, unpubDISCUSSION lished observations) and a constant infusion Liver transplantation in the pig is very of natural gastrin (Watson et al., submitted frequently accompanied by gastric ulcera- for publication) have proved to be useless in tion which occurs at the time of rejection our experience. Numerous etiologies have been proposed (8- 10 days) and is fatal. These studies have shown that highly selective vagotomy pro- for the susceptibility to gastric ulceration in tects against this ulceration almost com- the pig, and the relationship to biliary obpletely and that gastroenterostomy is partly struction has been clearly demonstrated by effective. Gastroenterostomy was, however, many authors [3, 131.Previous studies in this complicated by intestinal obstruction in laboratory have stressed the interrelationsome cases and hence highly selective vagot- ship between the absence of bile from the omy was recommended for ulcer preven- stomach, liver damage, and the incidence of
HOORN-HICKMAN
ET AL.: PIG LIVER TRANSPLANTATION-ULCER
ulceration. Each factor was found to contribute to ulceration, with a high incidence when both factors existed together [l]. Although acid hypersecretion has been shown to accompany the development of ulcers after bile duct ligation [l , 163there is not an associated rise of gas&in. The role of another acid secretagogue in the bile duct ligated pig is being investigated. The pigs of this series which had liver transplants were not tested for plasma gastrin Ievels, acid secretory responses, or the completeness of highly selective vagotomy as they were thought to be too complicated for such analyses to be of relevance in the determination of the pathogenesis of pars esophageal ulceration. The role of splenectomy was studied because it is included in our standard laboratory technique although some workers perform liver transplants without splenectomy [2,4]. It had been feared that addition of splenectomy might jeopardize the blood supply to the stomach but no complications suggestive of ischemia were seen in this series. The apparently prolonged survival of nonsplenectomized animals was not considered significant in view of the small number in this series and the fact that other workers have not been able to demonstrate a role for the spleen in the prolonged survival after liver transplantation in the pig [2, 4, 51. If the variable of splenectomy is discounted, the value of highly selective vagotomy becomes marked, viz., 100% incidence of ulceration without HSV and only 33% incidence with HSV. Thus although there is not complete protection, perhaps related to incomplete vagotomy in some cases, it appears that HSV is a useful adjunct to experimental liver transplantation in the pig. The prolonged survival with the pattern of reversible rejection which had been noted before [7, lo] was achieved as soon as gastric ulceration was prevented. ACKNOWLEDGEMENTS The continued advice and encouragement of Professor J. H. Louw, Head of the Division of Surgery, are
PREVENTION
499
acknowledged with pleasure. Biochemical tests were performed by Ms. J. Green, J. Fourie, C. Rose-Innes, P. van Heerden, and T. Davey, and histological preparations were made by Ms. S. Carstens and Mr. S. E. Abbott. The staff of the J. S. Marais Surgical Laboratory assisted with all operations. Financial support was received from the Medical Research Council of South Africa, the Cape Provincial Administration, the Harry Crossley and Mauerberger Foundations, and the Senate Research Committee of the University of Cape Town.
REFERENCES I. Amot, R. S. Hepatic and biliary factors in oesophagogastric ulceration of pigs. Ch.M. thesis. Univ. of Cape Town, 1974. 2. Battersby, C., Egerton, W. S., Balderson, G., Kerr, J. F., and Burnett, W. Another look at rejection in pig liver homografts. Surgery 76: 617, 1974. 3. Bicknell, E. J., Brooks, R. A., Osburn, J. A., and Whitehair, C. K. Extrahepatic biliary obstruction and gastric ulcers in pigs. Amer. .I. Vet. Res. 28: 943, 1967. 4. Caine, R. Y., White, J. J. O., Yoffa, D. E., Binns,
R. M., Maginn, R. R., Herbertson, B. M., Millard, P. R., Molina, V. P., and Davis, D. R. Prolonged survival of liver transplants in pigs. Brit. Med. J. 4: 645, 1967. 5. Caine, R. Y ., White, H. J. O., Binns, R. M.,
Herbertson, B. M., Millard, P. R., Pena, J., Salaman, J. R., Samuel, J. R., and Davis D. R. Immunosuppressive effects of the orthotopically transplanted porcine liver. Transplant. Proc. 1: 321, 1969. 6 Dent, D. M., Uys, C. J., Hickman, R., Saunders, S. J., and Terblanche, J. Gastric ulceration complicating experimental liver transplantation in the pig. J. Surg. Krs. II: 289, 1971. 7. Dent, D. M., Hickman, R., Uys, C. J., Saunders, S. J., and Terblanche. J. The natural history of liver auto- and allotransplantation in the unimmunosuppressed pig. Brit. J. Surg. 58: 407, 1971. 8. Gamier, J., Clot, J-P., and Chomette, G. Orthotopic transplantation of the pig liver. Surg. Gynec. Obstet. 130: 105, 1970. 9. Hickman, R., Terblanche, J., Simson, E., Dent,
D. M., and Saunders, S. J. Biochemical values in normal anaesthetised South African pigs. S. Afr. Med. J. 44: 531, 1970. 10. Hickman. R., Uys, C. J., and Terblanche, J. Pig
Liver transplantation-Extremes of response among pigs in one laboratory. S. Afr. J. Sci. 73: 116, 1977. 11 Johnston, D., and Wilkinson, A. R. Selective
vagotomy without a drainage procedure in the treatment of duodenal ulceration. Brit. J. Surg. 57: 289, 1970.
500
JOURNAL OF SURGICAL RESEARCH: VOL. 25, NO. 6, DECEMBER 1978
12. Kim, D. K., Lavarello, R. J., Rosch, P. P., and Fortner, J. G. Vagotomy and pyloroplasty in the prevention of gastric ulcers in pig liver transplantation. J. Surg. Res. 19: 5, 1975. 13. Kowalczyk, K. T. Aetiologic factors of gastric ulcers in swine. Amer. .I. Vet. Res. 30: 393, 1969. 14. Peacock, J. H., Immelman, E. J., Hobbs, K. E. F., Mitra, S. K., Bowes, J. B., and Hunt, A. C. Experimental appraisal of factors involved in the provision of donor livers. &it. Med. J. 1: 349, 1969. 15. Penny, R. H. C., Edwards, M. J., and Mulley, R. Gastric ulcer in the pig. &it. Vet. J. 128: 43, 1972. 16. Spilg, H. Orthotopic transplantation of the stored liver. Ch.M. thesis. Univ. of Cape Town, 1972.
17. Stadaas, J., Aune, S., and HatTner, J. F-W. Effects of proximal gastric vagotomy on intragastric pressure and adaptation in pigs. &and. J. Gastroenterol. 9: 479, 1976. 18. Swinscow, T. D. V. Statistics
al Square
One.
London: Brit. Med. Assoc., 1977. p. 31. 19. Watson, R. G. K., Vinik, A. I., Van Hoorn Hickman, R., and Terblanche, J. Bile duct ligation induced gastric ulceration-The role of bile. S. Afr. Med. J., in press, 1978. 20. Terblanche, J. and Van Hoorn Hickman, R. The Prevention of peptic ulceration by highly selective vacotomy in a new peptic ulcer model-The bile duct ligated pig. Surgery, in press, 1978.
OF SURGICAL
Gastric
RESEARCH
25, 496-500
(1978)
Ulceration Complicating Pig Liver Transplantation: Protective Effects of Gastroenterostomy or Highly Selective Vagotomyl
The
ROSEMARY VAN HOORN-HICKMAN, CH.M., W. A. VAN HooRN,M,B.CH.B., ANDJOHNTERBLANCHE,CH.M. Department
of Surgery & Medical Research Council Liver Research Group, Groote Schuur Hospital, Cape Town, South Africa Submitted
for publication
June 23, 1977
Gastric ulceration frequently complicates liver transplantation as well as other operations in pigs. These animals usually die of fatal hemorrhage within 10 days. The prevention of this complication by gastroenterostomy or highly selective vagotomy was studied in groups of transplanted pigs with or without splenectomy, and also in those with bile duct ligation. Gastroenterostomy reduced the incidence of ulceration associated with liver transplantation to 27%. whereas highly selective vagotomy (HSV) almost totally abolished ulceration. Animals with HSV and the spleen left in situ showed the long survival anticipated in the pig with indolent biochemical changes suggestive of lowgrade rejection. Thus animals could be studied for much longer periods and HSV should be considered as an adjunct to any procedure which is complicated by a high incidence ofgastric ulceration and hemorrhage.
The pig is notorious for its susceptibility to gastric ulceration both spontaneously [ 151 and in association with surgical procedures, especially liver transplantation 16, 121. The development of jaundice during rejection simulates the obstruction which results from bile duct ligation-a procedure known to result in ulceration in 100% of cases and in fatal gastrointestinal hemorrhage in 60% [ 11. Previous studies had suggested that gastroenterostomy might be protective [ 161but that neither the administration of cimetidine (Castles, unpublished observations) nor of intravenous gastrin [19] were protective. Highly selective vagotomy had been show to prevent ulceration in bile duct ligated pigs [20]. This study compares the use of gastroenterostomy or highly selective vagotomy in an attempt to prevent gastric ulceration in pigs after liver transplantation. The standard technique of liver r Reprint requests should be addressed to Dr. R. van Hoom-Hickman, Department of Surgery, Medical School, Observatory 7925, South Africa. 00224804/78/025(r04%$0
1.00/O
Copyright 0 1978 by Academic Press, Inc. All rights of reproduction in any form ressrved.
496
transplantation in this laboratory included splenectomy after use of the splenic vein for portosystemic bypass [7], but in order to exclude the role of gastric devascularisation following highly selective vagotomy plus liver transplant with splenectomy, the spleen was removed in some transplants and not in others. MATERIALS
AND METHODS
The pigs used were 6- to 8-week-old nonlitter-mates of Large White X Landrace breed, weighing 20 to 25 kg. After a 24 hr period of starvation, anesthesia was induced with thiopentone sodium (2-3 mgfkg) and was maintained with nitrous oxide and oxygen using a Magill-type circuit and intermittent positive pressure ventilation. Liver transplantation was performed by the standard techniques of this laboratory [9]. When the spleen was to be removed, the portosystemic bypass necessary for splanchnic decompression during the transplant was taken from the splenic vein to the jugular
HOORN-HICKMAN
ET AL.: PIG LIVER
TRANSPLANTATION-ULCER
vein, with subsequent splenectomy. When the spleen was left in situ, the bypass was inserted into the recipient portal vein and was removed just before the portal anastomosis was begun. Highly selective vagotomy (HSV) was performed as previously described [14, 211 being a modification of the method in humans of Johnston and Wilkinson [ 111.Particular care was taken to avoid the third pleural space which surrounds the oesophagus in the pig [ 151.
497
Postoperatively, animals received 2 liters of 10% invert sugar in Ringer’s lactate intravenously for 2 days with chloromycetin and penicillin (1 g each) daily for 5 days. Blood samples were taken daily for measurement of alkaline phosphatase, bilirubin, and aspartate aminotransferase as previously described [ 111. Autopsy was done as soon as possible after death. The animals were studied in the following groups:
1. Liver transplant + HSV (a) + splenectomy (b) - splenectomy 2. Liver transplant - HSV (a) + splenectomy (b) - splenectomy 3. Liver transplant (a) - gastroenterostomy (b) + gastroenterostomy 4. Bile duct ligation + gastroenterostomy RESULTS
PREVENTION
11 11 with splenectomy 6
group without splenectomy (2b), the mean ulcer incidence was 66% and the survival 16 -+ 8 days. The only two animals which did not develop ulcers showed no evidence of rejection and survived more than 21 days. In all animals which rejected comparison of the incidence of ulceration in those treated by highly selective vagotomy as compared with those not treated by HSV showed a total incidence of 33% with HSV and 100% without HSV (P > 0.05 using McNemar’s test). In a separate series of experiments gastroenterostomy had no effect on the ulcers which developed after bile duct ligation (group 4). In the animals with liver transplants the incidence of ulceration was 48% without gastroenterostomy (3a) and 27% when gastroenterostomy was added (3b). In groups 3b and 4 intestinal obstruction was noted in 2 of 11 and 2 of 6 pigs, respectively.
Incidence of ulceration and other causes of death (Table 1). The pars esophageal ulceration which occurred in these pigs was identical to that classically described [ 1, 31, viz., total denudation of the pars esophageal mucosa with massive intragastric hemorrhage. Animals in which highly selective vagotomy (HSV) was performed in addition to liver transplantation, showed a lower incidence of ulcers than those without HSV. In the HSV group with splenectomy (la) the ulcer incidence was 43% and the survival time 13 ? 4 days. In the HSV group without splenectomy (lb), the ulcer incidence was 20% and the mean survival was 35 2 10 days. Only one animal developed an ulcer which occurred in the 9th postoperative week; postmortem showed the unusual complication of bile duct stricture. Biochemistry In contrast when no highly selective vagotIn groups 1 and 2, there was no significant omy was done, 100% of the group with splenectomy (2a) developed ulcers with fatal difference in the biochemical changes hemorrhage and death at 9 +- 2 days. In the studied whether the spleen was removed or
498
JOURNAL OF SURGICAL RESEARCH: VOL. 25, NO. 6, DECEMBER 1978 TABLE 1 SURVIVAL
AND CAUSES OF DEATH
No.
Survival (days, mean 2 SE)
Percentage ulceration
I. Transplant + HSV (a) with splenectomy (b) without splenectomy
7 5
132 4 35 + 10
43 20
2. Transplant-HSV (a) with splenectomy (b) without splenectomy
6 6
9k 16-t
2 8
loo 0 in 2 lOttin
3. Transplant (a) - gastroenterostomy (b) + gastroenterostomy
4. Bile duct ligation + gastroenterostomy
11 11
ll+ 125
6 9
48 21
6
12
2
100
left intact, hence the data from each group were combined. In group 3 gastroenterostomy did not affect the biochemical changes and results are considered as one group. The levels of AAT, alkaline phosphatase, and bilirubin in the three groups of transplants were similar, showing increases from the 4th or Sth day. In the longer survivors of group 1, these iiver function tests showed intermittent fluctuations above normal. Animals with bile duct ligation showed progressive increase in bilirubin and alkaline phosphatase but no evidence of hepatocyte damage,
Other causes of death
2 pneumonia; 2 rejection 3 pneumonia; 1 sepsis
Nil Pneumonia without evidence of rejection Rejection 3 pneumonia; 3 rejection 2 pneumonia; 2 rejection 2 intestinal obstruction
2 intestinal obstruction
tion. The variable rejection response of the pig to liver transplantation [2, lo] has resulted in differing incidences of gastric ulceration. Each factor was found to contribute to ulceration, with a high incidence associated with rejection. In laboratories where the incidence of rejection is high 12, 81, gastric ulceration severely interferes with any sustained studies as animals die too early to be useful [5]. Calne et af. [4] have reported that truncal vagotomy prevents ulceration but this technique is difficult in the pig [14] and not widely used. Vagotomy and pyloroplasty has also been used with only limited success [12]. Cimetidine (Castles, unpubDISCUSSION lished observations) and a constant infusion Liver transplantation in the pig is very of natural gastrin (Watson et al., submitted frequently accompanied by gastric ulcera- for publication) have proved to be useless in tion which occurs at the time of rejection our experience. Numerous etiologies have been proposed (8- 10 days) and is fatal. These studies have shown that highly selective vagotomy pro- for the susceptibility to gastric ulceration in tects against this ulceration almost com- the pig, and the relationship to biliary obpletely and that gastroenterostomy is partly struction has been clearly demonstrated by effective. Gastroenterostomy was, however, many authors [3, 131.Previous studies in this complicated by intestinal obstruction in laboratory have stressed the interrelationsome cases and hence highly selective vagot- ship between the absence of bile from the omy was recommended for ulcer preven- stomach, liver damage, and the incidence of
HOORN-HICKMAN
ET AL.: PIG LIVER TRANSPLANTATION-ULCER
ulceration. Each factor was found to contribute to ulceration, with a high incidence when both factors existed together [l]. Although acid hypersecretion has been shown to accompany the development of ulcers after bile duct ligation [l , 163there is not an associated rise of gas&in. The role of another acid secretagogue in the bile duct ligated pig is being investigated. The pigs of this series which had liver transplants were not tested for plasma gastrin Ievels, acid secretory responses, or the completeness of highly selective vagotomy as they were thought to be too complicated for such analyses to be of relevance in the determination of the pathogenesis of pars esophageal ulceration. The role of splenectomy was studied because it is included in our standard laboratory technique although some workers perform liver transplants without splenectomy [2,4]. It had been feared that addition of splenectomy might jeopardize the blood supply to the stomach but no complications suggestive of ischemia were seen in this series. The apparently prolonged survival of nonsplenectomized animals was not considered significant in view of the small number in this series and the fact that other workers have not been able to demonstrate a role for the spleen in the prolonged survival after liver transplantation in the pig [2, 4, 51. If the variable of splenectomy is discounted, the value of highly selective vagotomy becomes marked, viz., 100% incidence of ulceration without HSV and only 33% incidence with HSV. Thus although there is not complete protection, perhaps related to incomplete vagotomy in some cases, it appears that HSV is a useful adjunct to experimental liver transplantation in the pig. The prolonged survival with the pattern of reversible rejection which had been noted before [7, lo] was achieved as soon as gastric ulceration was prevented. ACKNOWLEDGEMENTS The continued advice and encouragement of Professor J. H. Louw, Head of the Division of Surgery, are
PREVENTION
499
acknowledged with pleasure. Biochemical tests were performed by Ms. J. Green, J. Fourie, C. Rose-Innes, P. van Heerden, and T. Davey, and histological preparations were made by Ms. S. Carstens and Mr. S. E. Abbott. The staff of the J. S. Marais Surgical Laboratory assisted with all operations. Financial support was received from the Medical Research Council of South Africa, the Cape Provincial Administration, the Harry Crossley and Mauerberger Foundations, and the Senate Research Committee of the University of Cape Town.
REFERENCES I. Amot, R. S. Hepatic and biliary factors in oesophagogastric ulceration of pigs. Ch.M. thesis. Univ. of Cape Town, 1974. 2. Battersby, C., Egerton, W. S., Balderson, G., Kerr, J. F., and Burnett, W. Another look at rejection in pig liver homografts. Surgery 76: 617, 1974. 3. Bicknell, E. J., Brooks, R. A., Osburn, J. A., and Whitehair, C. K. Extrahepatic biliary obstruction and gastric ulcers in pigs. Amer. .I. Vet. Res. 28: 943, 1967. 4. Caine, R. Y., White, J. J. O., Yoffa, D. E., Binns,
R. M., Maginn, R. R., Herbertson, B. M., Millard, P. R., Molina, V. P., and Davis, D. R. Prolonged survival of liver transplants in pigs. Brit. Med. J. 4: 645, 1967. 5. Caine, R. Y ., White, H. J. O., Binns, R. M.,
Herbertson, B. M., Millard, P. R., Pena, J., Salaman, J. R., Samuel, J. R., and Davis D. R. Immunosuppressive effects of the orthotopically transplanted porcine liver. Transplant. Proc. 1: 321, 1969. 6 Dent, D. M., Uys, C. J., Hickman, R., Saunders, S. J., and Terblanche, J. Gastric ulceration complicating experimental liver transplantation in the pig. J. Surg. Krs. II: 289, 1971. 7. Dent, D. M., Hickman, R., Uys, C. J., Saunders, S. J., and Terblanche. J. The natural history of liver auto- and allotransplantation in the unimmunosuppressed pig. Brit. J. Surg. 58: 407, 1971. 8. Gamier, J., Clot, J-P., and Chomette, G. Orthotopic transplantation of the pig liver. Surg. Gynec. Obstet. 130: 105, 1970. 9. Hickman, R., Terblanche, J., Simson, E., Dent,
D. M., and Saunders, S. J. Biochemical values in normal anaesthetised South African pigs. S. Afr. Med. J. 44: 531, 1970. 10. Hickman. R., Uys, C. J., and Terblanche, J. Pig
Liver transplantation-Extremes of response among pigs in one laboratory. S. Afr. J. Sci. 73: 116, 1977. 11 Johnston, D., and Wilkinson, A. R. Selective
vagotomy without a drainage procedure in the treatment of duodenal ulceration. Brit. J. Surg. 57: 289, 1970.
500
JOURNAL OF SURGICAL RESEARCH: VOL. 25, NO. 6, DECEMBER 1978
12. Kim, D. K., Lavarello, R. J., Rosch, P. P., and Fortner, J. G. Vagotomy and pyloroplasty in the prevention of gastric ulcers in pig liver transplantation. J. Surg. Res. 19: 5, 1975. 13. Kowalczyk, K. T. Aetiologic factors of gastric ulcers in swine. Amer. .I. Vet. Res. 30: 393, 1969. 14. Peacock, J. H., Immelman, E. J., Hobbs, K. E. F., Mitra, S. K., Bowes, J. B., and Hunt, A. C. Experimental appraisal of factors involved in the provision of donor livers. &it. Med. J. 1: 349, 1969. 15. Penny, R. H. C., Edwards, M. J., and Mulley, R. Gastric ulcer in the pig. &it. Vet. J. 128: 43, 1972. 16. Spilg, H. Orthotopic transplantation of the stored liver. Ch.M. thesis. Univ. of Cape Town, 1972.
17. Stadaas, J., Aune, S., and HatTner, J. F-W. Effects of proximal gastric vagotomy on intragastric pressure and adaptation in pigs. &and. J. Gastroenterol. 9: 479, 1976. 18. Swinscow, T. D. V. Statistics
al Square
One.
London: Brit. Med. Assoc., 1977. p. 31. 19. Watson, R. G. K., Vinik, A. I., Van Hoorn Hickman, R., and Terblanche, J. Bile duct ligation induced gastric ulceration-The role of bile. S. Afr. Med. J., in press, 1978. 20. Terblanche, J. and Van Hoorn Hickman, R. The Prevention of peptic ulceration by highly selective vacotomy in a new peptic ulcer model-The bile duct ligated pig. Surgery, in press, 1978.
