IOURNAL
OF SURGICAI
23, 321-331 (1977)
RFSEARCH
Choledochoduodenostomy in the Rat with Obstructive Jaundice C.J. RYAN,THANTHAN,AND University
L.H.
Department of Surgery, Royal InJirmaty,
BLUMGART'
Glasgow,
G4 OSF, Scotiand
Submitted for publication November 17, 1976
All surgical procedures were carried out under ether anesthesia and were clean but not sterile. Operative procedures were performed using a Zeiss operating microscope, x 6 magnification. Technique for bile duct ligation. The bile duct was ligated and divided between ligatures by the method of Lee [7]. This method ensures permanent obstruction of biliary flow from the liver; in order to produce the same degree of obstruction in each rat, the most proximal ligature was placed at the same position along the length of the common bile duct [6. 91. Technique for choledochoduodenostomy. The abdomen was opened through a midline incision. The median and left lateral lobes of the liver were mobilized and delivered upwards onto the anterior abdominal wall. A section of duodenum was selected approximately 2 cm from the pyioric sphincter. A purse-string suture 2-3 mm in diameter was made in the duodenum using 7-O silk mounted on an &mm atraumatic needle (Ethicon W6594) but was not tied. The biliary sac created by the previous bile duct ligation was freed from the surrounding adherent tissue. A 17-gaugeneedle was introduced into the sac and the conMATERIALS AND METHODS tents were aspirated. A 7-O silk suture Male Sprague-Dawley rats weighing be- was passed through the edge of the sac at tween 190 and 230 g were used. The ani- the point of aspiration and traction was mals were maintained in groups of two applied distally. A small incision was made under controlled conditions of temperature in the sac and the plain end of a shouldered and humidity and fed ad lib. on rat cube Teflon drainage tube (0.035-mm internal diet 41B (Macfarlane Robson Ltd.). diameter x 7-mm length, Richard Manufacturing Co., Memphis, Tennessee) was 1Address correspondence to Professor Blumgart. inserted (Fig. 1) and tied securely in posiObstruction of the biliary tree is followed by important biochemical and pathological changes which influence treatment and prognosis. The longer the period of obstruction, the more severe the changes which occur and the greater the morbidity and mortality [4, 51. Not only is biliary obstruction followed by jaundice and changes in liver function, but there are associated changes in other organs, including significant alterations in renal function [l, 4, 81 and in the process of healing [7, 10, 111. Relief of biliary ductal obstruction in clinical practice is usually followed by regression of the associated pathological and biochemical abnormalities. However, since many experimental studies of liver function are conducted in rats, it is of some importance to develop methods which will allow serial study of the effects of biliary obstruction and its relief in these animals. This study reports the development of a technique for choledochoduodenostomy in the rat with obstructive jaundice and presents preliminary studies of liver function during and after relief of biliary obstruction.
321 Copyright All rights
0 1977 by Academic Press, Inc. of reproduction in any form reserved.
ISSN 0022-4804
322
JOURNAL OF SURGICAL RESEARCH: VOL. 23, NO. 5, NOVEMBER
1977
FIG. 1. Positioning of the plain end of the Teflon drain tube into the biliary sac. Note the importance of traction via the 7-O silk suture.
tion using a 3-O silk suture. Traction was then applied by means of this suture in order to approximate the Teflon tube to the duodenum. An opening was made in the duodenum within the center of the pursestring suture, and the cuffed end of the drainage tube was inserted (Fig. 2) and tied in position by means of the purse-string suture. Some manipulation of the duodenum and of the Teflon drainage tube was often necessary at this point. The free ends of the sutures were divided leaving the Teflon tube bridging the gap between the biliary sac and the duodenum (Fig. 3). The abdominal would was then closed. Biochemical estimations. Serum bilirubin, alkaline phosphatase, serum glutamic oxaloacetic transaminase (SGOT), and serum glutamic-pyruvic transaminase (SGFT) levels were measured. The serum
enzymes were estimated using microtechniques modified from Boehringer optomized biochemical test combination kits at 37°C (Boehringer Corporation (London) Ltd.) and using the Gilford enzyme rate analyzer system (Gilford Instrument Laboratories, Inc., Oberlin, Ohio). The bilirubin was estimated using a microtechnique modified from the method of Brayshaw [2] and measured on the Gilford 300N spectrophotometer from the above system. Experimental
Design
The animals were studied in three groups. Group Z (6 animals). A bile duct ligation was carried out by the method described and the animals were sacrificed 2 weeks postoperatively, for histological examination only.
RYAN, THAN, AND BLUMGART:
CHOLEDOCHODUODENOSTOMY
IN THE RAT
323
FIG. 2. Positioning of the cuffed end of the Teflon drain tube into the duodenum within the center of the pursestring suture. Note the importance of traction via the 3-O silk suture.
Group ZZ (10 animals). The animals were subjected to a bile duct ligation and 2 weeks later choledochoduodenostomy was carried out. The animals were then allowed to survive for a further period of 5 weeks. Group ZZZ(5 animals). The animals were subjected to a bile duct ligation and then 2 weeks after operation laparotomy only was performed. The animals were allowed to survive for a further 3 weeks. Groups II and III were weighed and blood samples were taken preoperatively
and at weekly intervals thereafter. At sacrifice, each animal was anesthetized with ether and the operative field was examined. The liver was excized, blotted, weighed, and fixed in 10% form01 saline. RESULTS
During the first postoperative week following bile duct ligation, all 21 animals were clearly jaundiced. At 2 weeks the distal remnant of the bile duct remained
324
JOURNAL OF SURGICAL RESEARCH: VOL. 23, NO. 5, NOVEMBER
1977
FIG. 3. Completed choledochoduodenostomy.
normal with no apparent obstruction to pancreatic secretion. However, the proximal bile duct was grossly distended and displaced the adjacent liver lobes. On aspiration of the biliary sac (Groups I and II), 1.25-4.0 ml of bile was obtained. There was no evidence of ascites in all 21 animals.
and alert throughout the experimental period and indeed 2 of the 10 were not sacrificed and were still alive 12 weeks following choledochoduodenostomy. Group III. One animal died during the second postoperative week after laparotomy. The remaining animals were sacrificed 3 weeks later.
Survival Group ZZ. Of the 10 animals in this group,
one died 4 weeks after choledochoduodenostomy. The remaining animals were healthy
Patency of Anastomosis
The choledochoduodenostomy was examined at sacrifice of seven of the animals in
RYAN, THAN, AND BLUMGART:
CHOLEDOCHODUODENOSTOMY
IN THE RAT
325
FIG. 4. Choledochoduodenostomy 5 weeks following surgery. Note that the Teflon drain tube is still in position.
Group II. The anastomosis remained patent in every case (Fig. 4). In four of the animals the Teflon tube was still in situ but in the remaining three it had passed along the intestinal tract. In these latter three animals, the fistula remained patent (Fig. 5). While no gross changes were found at postmortem in the animals subjected to choledochoduodenostomy, animals in Group III, subjected to laparotomy only, had up to 36 ml of ascitic fluid present in the peritoneal cavity at sacrifice. The bile duct in each of these animals was grossly distended, com-
pressing adjacent liver lobes, and the biliary sac protruded in front of the stomach and duodenum, stretching the portal vein and hepatic artery. This distended sac contained up to 20 ml of turbid bile. Changes in Body Weight Animals in both Groups II and III lost weight during the first postoperative week and thereafter regained a normal growth curve so that 5 weeks following the first operative procedure (Fig 6) there was no
326
JOURNAL OF SURGICAL RESEARCH: VOL. 23, NO. 5, NOVEMBER
1977
FIG. 5. Section of duodenum opened longitudinally to show patent choledochoduodenostomy when the Teflon drain tube had become dislodged.
in animals subjected to bile duct ligation, Group I (Fig. 7). These changes were more severe in animals in which bile duct ligation Liver Weight and Histology was maintained for 5 weeks, Group III (Figs. Liver weight was expressed as a percent- 8a and b). Indeed, in some animals there age of body weight at sacrifice and it was was a marked degree of ductular proliferafound that bile duct ligation was associated tion so that the normal lobular architecture with an increase in liver weight as a percent- had almost disappeared. By contrast, the age of body weight (Table I). Histological histological changes seen 5 weeks after study revealed bile duct proliferation and choledochoduodenostomy, Group II (Fig. periportal fibrosis with acute on chronic 9), would suggest that the relief of biliary inflammatory changes in the periportal areas ductal obstruction arrests the progression of statistical difference observed in the body weight of animals in Groups II and III.
RYAN, THAN, AND BLUMGART: -
Group1 Choledochoduodenortomy
C---.
Groupli7 Loparofomy
CHOLEDOCHODUODENOSTOMY
327
IN THE RAT
TABLE 1 LIVER WEIGHT AT SACRIFICE
Number of animals Mean liver weight (% of body weight 2 SD)
Group II
Group III
7
4
5.36 z!z0.24 4.38 + 0.40 0.005 >P > 0.001
the lesions and may permit regression of lesions that are already present. Changes in Liver Function
FIG. 6. Body weights of animals in Groups II and III.
Table 2 gives the changes in liver function with time for Groups II and III. The results are expressed as means + the standard deviation. Following bile duct ligation, there was elevation in serum bilirubin, serum alka-
FIG. 7. Histological section of rat liver 2 weeks after bile duct ligation (H and E stain). x 125.
JOURNAL
OF SURGICAL
RESEARCH:
VOL. 23, NO. 5, NOVEMBER
1977
line phosphatase, SCOT, and SGPT levels. Following choledochoduodenostomy, serum bilirubin and serum enzymes returned to normal within 1 week and in two animals, still alive at 12 weeks after operation, there was normal liver function. By contrast, in animals with obstructive jaundice in which laparotomy only was performed, serum bilirubin levels remained persistently elevated until sacrifice. These findings are also shown graphically in Fig. 10. The same was also true of SGOT and SGFT. The alkaline phosphatase levels, however, were found to return towards normal limits after laparotomy. DISCUSSION Biliary tract obstruction and its relief are common in clinical practice, and experimental study of the pathophysiological changes occurring in the liver and other organs is of importance. The technique described allows the performance of a simple choledochoduodenostomy in the rat with obstructive jaundice and provides the opportunity to study serial changes in the same animal. The operative procedure is well tolerated and has a negligible mortality. Following choledochoduodenostomy, rats have been followed for 12 weeks and appear healthy. Bile duct ligation in the rat is not followed by marked changes in body weight. Hyperbilirubinemia occurs and is associated with a rise in alkaline phosphatase, SGOT, and SGPT. There are progressive changes in liver histology mainly characterized by biliary ductal proliferation. The changes are similar to those described by Weinbren [13] and Cameron and Prasad [3]. Other workers [3, 121 have shown that single-ligature ligation of the rat’s common bile duct allows reestablishment of the lumen in some animals within an unknown interval of time after operation, and that this allows recovery of liver function and of the histological pattern of the liver towards normal. Our studies confirm that such reversal of biochemical and histological changes can
RYAN, THAN, AND BLUMGART:
CHOLEDOCHODUODENOSTOMY
IN THE RAT
329
FIG. 8. Histological sections of rat liver 5 weeks after bile duct ligation (H and E stain). (a) x 110; (b) x 450.
330
JOURNAL OF SURGICAL RESEARCH: VOL. 23, NO. 5, NOVEMBER
1977
FIG. 9. Histological section of rat liver 5 weeks after choledochoduodenostomy (H and E stain). x 125.
-
take place in animals subjected to obstruction of the bile duct for a period of 2 weeks.
Group I[ CholedllchoduodenorPmy
SUMMARY Mean
A method of choledochoduodenostomy for the relief of experimentally induced obstructive jaundice in the rat is described. Using this technique, biochemical changes resulting from extrahepatic biliary ductal obstruction were completely relieved. Histological changes in the liver also appeared to regress following choledochoduodenostomy.
f SD
ACKNOWLEDGMENT Weeks “I ’ MeD”‘, Llgab”
i
3
4
s
6
We gratefully acknowledge the advice and assistance generously provided by Dr. A. L. C. McLay of the Department of Pathology, Royal Infirmary, Glasgow.
7
C holedochoduodenortomy 0, LLlp(1‘01only
FIG. 10. Serum bilirubin levels in animals in Groups II and III.
REFERENCES 1. Allison, M. E. M., Moss, N. G., Fraser, M. M., Lloyd-Jones, W., Ryan, C. J., Dobbie, J. W.,
RYAN, THAN, AND BLUMGART:
CHOLEDOCHODUODENOSTOMY
Kennedy, A. C., and Blumgart, L. H. Renal function in obstructive jaundice: A clinical and micropuncture study. In Sixth lnfernnfionaf Congress of Nephrology
(Firenze),
Abstracts
of Symposia,
106. 1975. 2. Brayshaw. B. J. Manualand automated techniques for total and conjugated bilirubin. Med. Lab. Tech. 28: 133, 1971. 3. Cameron, G. R., and Prasad, L. B. M. Recovery from biliary obstruction after spontaneous restoration of the obstructed common bile duct. J. P&o/. Bacterial.
80: 127, 1960.
4. Dawson, J. L. Acute post-operative renal failure in obstructive jaundice. J. R. Call. Surg. 42: 163, 1968. 5. Dawson, J. L. Surgical aspects of jaundice. &if. Med. J. 1: 228, 1970.
6. Koch-Waser, D., Meyer, K. A., Yesinick, C. Y., and Popper, H. Influence of the site of experimental biliary obstruction upon functional and morphologic hepatic injury. Lab. Invest. 1: 324, 1952. 7. Lee, E. The effect of obstructive jaundice on the
IN THE RAT
331
migration of retroblasts into early experimental granulomata. &it. J. Surg. 59: 875, 1971. 8. Moss, N. E., Fraser, M., Ryan, C. J., Kennedy, A. C., Allison, M. E. M., and Blumgart, L. H. Renal function before and after haemorrhage in rats with chronic bile duct obstruction: A micropuncture study. &it. 1. Surg. 62: 653, 1975. 9. Sasaki, H. Experimental obstructive jaundice in rats. Morphogenetic studies on biliary cirrhosis. Acta Med. Univ. Kyoto 37: 59, 1960.
10. Than, T., McGee, J. O’D., Sokhi, G. S., Patrick, R. S., and Blumgart. L,. H. Skin prolyl hydroxylase in patients with obstructive jaundice. Loncef 2: 807, 1974.
II. Than. T. Unpublished observation. 12. Trams, E. G., and Symeonidis, A. Morphological and functional changes in the livers of rats after ligation or excision of the common bile duct. Amer. J. Pathol. 33: 13, 1957. 13. Weinbren, K. The effect of bile duct obstruction and regeneration of the rat’s liver. &it. J. Exp. Pathol.
34: 280, 1953.
OF SURGICAI
23, 321-331 (1977)
RFSEARCH
Choledochoduodenostomy in the Rat with Obstructive Jaundice C.J. RYAN,THANTHAN,AND University
L.H.
Department of Surgery, Royal InJirmaty,
BLUMGART'
Glasgow,
G4 OSF, Scotiand
Submitted for publication November 17, 1976
All surgical procedures were carried out under ether anesthesia and were clean but not sterile. Operative procedures were performed using a Zeiss operating microscope, x 6 magnification. Technique for bile duct ligation. The bile duct was ligated and divided between ligatures by the method of Lee [7]. This method ensures permanent obstruction of biliary flow from the liver; in order to produce the same degree of obstruction in each rat, the most proximal ligature was placed at the same position along the length of the common bile duct [6. 91. Technique for choledochoduodenostomy. The abdomen was opened through a midline incision. The median and left lateral lobes of the liver were mobilized and delivered upwards onto the anterior abdominal wall. A section of duodenum was selected approximately 2 cm from the pyioric sphincter. A purse-string suture 2-3 mm in diameter was made in the duodenum using 7-O silk mounted on an &mm atraumatic needle (Ethicon W6594) but was not tied. The biliary sac created by the previous bile duct ligation was freed from the surrounding adherent tissue. A 17-gaugeneedle was introduced into the sac and the conMATERIALS AND METHODS tents were aspirated. A 7-O silk suture Male Sprague-Dawley rats weighing be- was passed through the edge of the sac at tween 190 and 230 g were used. The ani- the point of aspiration and traction was mals were maintained in groups of two applied distally. A small incision was made under controlled conditions of temperature in the sac and the plain end of a shouldered and humidity and fed ad lib. on rat cube Teflon drainage tube (0.035-mm internal diet 41B (Macfarlane Robson Ltd.). diameter x 7-mm length, Richard Manufacturing Co., Memphis, Tennessee) was 1Address correspondence to Professor Blumgart. inserted (Fig. 1) and tied securely in posiObstruction of the biliary tree is followed by important biochemical and pathological changes which influence treatment and prognosis. The longer the period of obstruction, the more severe the changes which occur and the greater the morbidity and mortality [4, 51. Not only is biliary obstruction followed by jaundice and changes in liver function, but there are associated changes in other organs, including significant alterations in renal function [l, 4, 81 and in the process of healing [7, 10, 111. Relief of biliary ductal obstruction in clinical practice is usually followed by regression of the associated pathological and biochemical abnormalities. However, since many experimental studies of liver function are conducted in rats, it is of some importance to develop methods which will allow serial study of the effects of biliary obstruction and its relief in these animals. This study reports the development of a technique for choledochoduodenostomy in the rat with obstructive jaundice and presents preliminary studies of liver function during and after relief of biliary obstruction.
321 Copyright All rights
0 1977 by Academic Press, Inc. of reproduction in any form reserved.
ISSN 0022-4804
322
JOURNAL OF SURGICAL RESEARCH: VOL. 23, NO. 5, NOVEMBER
1977
FIG. 1. Positioning of the plain end of the Teflon drain tube into the biliary sac. Note the importance of traction via the 7-O silk suture.
tion using a 3-O silk suture. Traction was then applied by means of this suture in order to approximate the Teflon tube to the duodenum. An opening was made in the duodenum within the center of the pursestring suture, and the cuffed end of the drainage tube was inserted (Fig. 2) and tied in position by means of the purse-string suture. Some manipulation of the duodenum and of the Teflon drainage tube was often necessary at this point. The free ends of the sutures were divided leaving the Teflon tube bridging the gap between the biliary sac and the duodenum (Fig. 3). The abdominal would was then closed. Biochemical estimations. Serum bilirubin, alkaline phosphatase, serum glutamic oxaloacetic transaminase (SGOT), and serum glutamic-pyruvic transaminase (SGFT) levels were measured. The serum
enzymes were estimated using microtechniques modified from Boehringer optomized biochemical test combination kits at 37°C (Boehringer Corporation (London) Ltd.) and using the Gilford enzyme rate analyzer system (Gilford Instrument Laboratories, Inc., Oberlin, Ohio). The bilirubin was estimated using a microtechnique modified from the method of Brayshaw [2] and measured on the Gilford 300N spectrophotometer from the above system. Experimental
Design
The animals were studied in three groups. Group Z (6 animals). A bile duct ligation was carried out by the method described and the animals were sacrificed 2 weeks postoperatively, for histological examination only.
RYAN, THAN, AND BLUMGART:
CHOLEDOCHODUODENOSTOMY
IN THE RAT
323
FIG. 2. Positioning of the cuffed end of the Teflon drain tube into the duodenum within the center of the pursestring suture. Note the importance of traction via the 3-O silk suture.
Group ZZ (10 animals). The animals were subjected to a bile duct ligation and 2 weeks later choledochoduodenostomy was carried out. The animals were then allowed to survive for a further period of 5 weeks. Group ZZZ(5 animals). The animals were subjected to a bile duct ligation and then 2 weeks after operation laparotomy only was performed. The animals were allowed to survive for a further 3 weeks. Groups II and III were weighed and blood samples were taken preoperatively
and at weekly intervals thereafter. At sacrifice, each animal was anesthetized with ether and the operative field was examined. The liver was excized, blotted, weighed, and fixed in 10% form01 saline. RESULTS
During the first postoperative week following bile duct ligation, all 21 animals were clearly jaundiced. At 2 weeks the distal remnant of the bile duct remained
324
JOURNAL OF SURGICAL RESEARCH: VOL. 23, NO. 5, NOVEMBER
1977
FIG. 3. Completed choledochoduodenostomy.
normal with no apparent obstruction to pancreatic secretion. However, the proximal bile duct was grossly distended and displaced the adjacent liver lobes. On aspiration of the biliary sac (Groups I and II), 1.25-4.0 ml of bile was obtained. There was no evidence of ascites in all 21 animals.
and alert throughout the experimental period and indeed 2 of the 10 were not sacrificed and were still alive 12 weeks following choledochoduodenostomy. Group III. One animal died during the second postoperative week after laparotomy. The remaining animals were sacrificed 3 weeks later.
Survival Group ZZ. Of the 10 animals in this group,
one died 4 weeks after choledochoduodenostomy. The remaining animals were healthy
Patency of Anastomosis
The choledochoduodenostomy was examined at sacrifice of seven of the animals in
RYAN, THAN, AND BLUMGART:
CHOLEDOCHODUODENOSTOMY
IN THE RAT
325
FIG. 4. Choledochoduodenostomy 5 weeks following surgery. Note that the Teflon drain tube is still in position.
Group II. The anastomosis remained patent in every case (Fig. 4). In four of the animals the Teflon tube was still in situ but in the remaining three it had passed along the intestinal tract. In these latter three animals, the fistula remained patent (Fig. 5). While no gross changes were found at postmortem in the animals subjected to choledochoduodenostomy, animals in Group III, subjected to laparotomy only, had up to 36 ml of ascitic fluid present in the peritoneal cavity at sacrifice. The bile duct in each of these animals was grossly distended, com-
pressing adjacent liver lobes, and the biliary sac protruded in front of the stomach and duodenum, stretching the portal vein and hepatic artery. This distended sac contained up to 20 ml of turbid bile. Changes in Body Weight Animals in both Groups II and III lost weight during the first postoperative week and thereafter regained a normal growth curve so that 5 weeks following the first operative procedure (Fig 6) there was no
326
JOURNAL OF SURGICAL RESEARCH: VOL. 23, NO. 5, NOVEMBER
1977
FIG. 5. Section of duodenum opened longitudinally to show patent choledochoduodenostomy when the Teflon drain tube had become dislodged.
in animals subjected to bile duct ligation, Group I (Fig. 7). These changes were more severe in animals in which bile duct ligation Liver Weight and Histology was maintained for 5 weeks, Group III (Figs. Liver weight was expressed as a percent- 8a and b). Indeed, in some animals there age of body weight at sacrifice and it was was a marked degree of ductular proliferafound that bile duct ligation was associated tion so that the normal lobular architecture with an increase in liver weight as a percent- had almost disappeared. By contrast, the age of body weight (Table I). Histological histological changes seen 5 weeks after study revealed bile duct proliferation and choledochoduodenostomy, Group II (Fig. periportal fibrosis with acute on chronic 9), would suggest that the relief of biliary inflammatory changes in the periportal areas ductal obstruction arrests the progression of statistical difference observed in the body weight of animals in Groups II and III.
RYAN, THAN, AND BLUMGART: -
Group1 Choledochoduodenortomy
C---.
Groupli7 Loparofomy
CHOLEDOCHODUODENOSTOMY
327
IN THE RAT
TABLE 1 LIVER WEIGHT AT SACRIFICE
Number of animals Mean liver weight (% of body weight 2 SD)
Group II
Group III
7
4
5.36 z!z0.24 4.38 + 0.40 0.005 >P > 0.001
the lesions and may permit regression of lesions that are already present. Changes in Liver Function
FIG. 6. Body weights of animals in Groups II and III.
Table 2 gives the changes in liver function with time for Groups II and III. The results are expressed as means + the standard deviation. Following bile duct ligation, there was elevation in serum bilirubin, serum alka-
FIG. 7. Histological section of rat liver 2 weeks after bile duct ligation (H and E stain). x 125.
JOURNAL
OF SURGICAL
RESEARCH:
VOL. 23, NO. 5, NOVEMBER
1977
line phosphatase, SCOT, and SGPT levels. Following choledochoduodenostomy, serum bilirubin and serum enzymes returned to normal within 1 week and in two animals, still alive at 12 weeks after operation, there was normal liver function. By contrast, in animals with obstructive jaundice in which laparotomy only was performed, serum bilirubin levels remained persistently elevated until sacrifice. These findings are also shown graphically in Fig. 10. The same was also true of SGOT and SGFT. The alkaline phosphatase levels, however, were found to return towards normal limits after laparotomy. DISCUSSION Biliary tract obstruction and its relief are common in clinical practice, and experimental study of the pathophysiological changes occurring in the liver and other organs is of importance. The technique described allows the performance of a simple choledochoduodenostomy in the rat with obstructive jaundice and provides the opportunity to study serial changes in the same animal. The operative procedure is well tolerated and has a negligible mortality. Following choledochoduodenostomy, rats have been followed for 12 weeks and appear healthy. Bile duct ligation in the rat is not followed by marked changes in body weight. Hyperbilirubinemia occurs and is associated with a rise in alkaline phosphatase, SGOT, and SGPT. There are progressive changes in liver histology mainly characterized by biliary ductal proliferation. The changes are similar to those described by Weinbren [13] and Cameron and Prasad [3]. Other workers [3, 121 have shown that single-ligature ligation of the rat’s common bile duct allows reestablishment of the lumen in some animals within an unknown interval of time after operation, and that this allows recovery of liver function and of the histological pattern of the liver towards normal. Our studies confirm that such reversal of biochemical and histological changes can
RYAN, THAN, AND BLUMGART:
CHOLEDOCHODUODENOSTOMY
IN THE RAT
329
FIG. 8. Histological sections of rat liver 5 weeks after bile duct ligation (H and E stain). (a) x 110; (b) x 450.
330
JOURNAL OF SURGICAL RESEARCH: VOL. 23, NO. 5, NOVEMBER
1977
FIG. 9. Histological section of rat liver 5 weeks after choledochoduodenostomy (H and E stain). x 125.
-
take place in animals subjected to obstruction of the bile duct for a period of 2 weeks.
Group I[ CholedllchoduodenorPmy
SUMMARY Mean
A method of choledochoduodenostomy for the relief of experimentally induced obstructive jaundice in the rat is described. Using this technique, biochemical changes resulting from extrahepatic biliary ductal obstruction were completely relieved. Histological changes in the liver also appeared to regress following choledochoduodenostomy.
f SD
ACKNOWLEDGMENT Weeks “I ’ MeD”‘, Llgab”
i
3
4
s
6
We gratefully acknowledge the advice and assistance generously provided by Dr. A. L. C. McLay of the Department of Pathology, Royal Infirmary, Glasgow.
7
C holedochoduodenortomy 0, LLlp(1‘01only
FIG. 10. Serum bilirubin levels in animals in Groups II and III.
REFERENCES 1. Allison, M. E. M., Moss, N. G., Fraser, M. M., Lloyd-Jones, W., Ryan, C. J., Dobbie, J. W.,
RYAN, THAN, AND BLUMGART:
CHOLEDOCHODUODENOSTOMY
Kennedy, A. C., and Blumgart, L. H. Renal function in obstructive jaundice: A clinical and micropuncture study. In Sixth lnfernnfionaf Congress of Nephrology
(Firenze),
Abstracts
of Symposia,
106. 1975. 2. Brayshaw. B. J. Manualand automated techniques for total and conjugated bilirubin. Med. Lab. Tech. 28: 133, 1971. 3. Cameron, G. R., and Prasad, L. B. M. Recovery from biliary obstruction after spontaneous restoration of the obstructed common bile duct. J. P&o/. Bacterial.
80: 127, 1960.
4. Dawson, J. L. Acute post-operative renal failure in obstructive jaundice. J. R. Call. Surg. 42: 163, 1968. 5. Dawson, J. L. Surgical aspects of jaundice. &if. Med. J. 1: 228, 1970.
6. Koch-Waser, D., Meyer, K. A., Yesinick, C. Y., and Popper, H. Influence of the site of experimental biliary obstruction upon functional and morphologic hepatic injury. Lab. Invest. 1: 324, 1952. 7. Lee, E. The effect of obstructive jaundice on the
IN THE RAT
331
migration of retroblasts into early experimental granulomata. &it. J. Surg. 59: 875, 1971. 8. Moss, N. E., Fraser, M., Ryan, C. J., Kennedy, A. C., Allison, M. E. M., and Blumgart, L. H. Renal function before and after haemorrhage in rats with chronic bile duct obstruction: A micropuncture study. &it. 1. Surg. 62: 653, 1975. 9. Sasaki, H. Experimental obstructive jaundice in rats. Morphogenetic studies on biliary cirrhosis. Acta Med. Univ. Kyoto 37: 59, 1960.
10. Than, T., McGee, J. O’D., Sokhi, G. S., Patrick, R. S., and Blumgart. L,. H. Skin prolyl hydroxylase in patients with obstructive jaundice. Loncef 2: 807, 1974.
II. Than. T. Unpublished observation. 12. Trams, E. G., and Symeonidis, A. Morphological and functional changes in the livers of rats after ligation or excision of the common bile duct. Amer. J. Pathol. 33: 13, 1957. 13. Weinbren, K. The effect of bile duct obstruction and regeneration of the rat’s liver. &it. J. Exp. Pathol.
34: 280, 1953.
