Canine Gallbladder Bile Effects of Proximal Gastric Vagotomy, Truncal Vagotomy, and Truncal Vagotomy With Pyloroplasty on Volume and Composition Bruce G.
Wilbur, MD; Francisco C. Gomez, MD; Ronald K. Tompkins,
Three groups of four dogs each underwent proximal gastric vagotomy, truncal vagotomy, or truncal vagotomy with pyloroplasty. Two dogs had sham operations. Gallbladder bile was aspirated and measured. Aliquots were cultured and assayed for cholesterol, phospholipid, and bile salts initially and at subsequent laparotomies. Both truncal vagotomy groups showed marked increases in aspirate volume at subsequent laparotomies. The sham and proximal gastric vagotomy groups showed a small initial decrease in mean aspirate volume without further significant changes. When the bile assay data were plotted on triangular coordinates, all points for all groups remained well within the area of cholesterol solubility. Nevertheless, two dogs in each truncal vagotomy group were found to have gallstones. No stones were found in the sham and proximal gastric vagotomy groups. Proximal gastric vagotomy appears to preserve fasting gallbladder bile volume and does not alter bile composition in the dog.
reported vagotomy Truncal tendency cholelithiasis has been
to increase the in man.14 Alterations in motility of the biliary tract and increases in the lithogenicity of bile are mechanisms by which vagotomy may predispose to an increased rate of gallstone formation. Little evidence has been presented concerning the effect of proximal gastric vagotomy on the composition and vol¬ ume of gallbladder bile. The present study was designed to compare effects of proximal gastric vagotomy, truncal vagotomy, and truncal vagotomy and pyloroplasty on the volume and composition of gallbladder bile in dogs.
to
Accepted
for publication March 7, 1975. From the Biliary Lipid Laboratory, Department of Surgery, UCLA School of Medicine, Los Angeles. Read before the annual meeting of the Southern California Chapter of the American College of Surgeons, Santa Barbara, Calif, Jan 17, 1975. Reprint requests to Biliary Lipid Laboratory, Department of Surgery, UCLA School of Medicine, Los Angeles, CA 90024 (Drs. Wilbur and Tomp-
kins).
MD
METHODS Fourteen adult mongrel dogs weighing 10 to 15 kg comprised the study group. Two dogs that underwent sham operations with aspiration of the gallbladder served as longitudinal controls (group 1). Twelve dogs were divided into three groups (groups 2,3, and 4) of four dogs each. Dogs in group 1 were operated on after an 18-hour fast, and the gallbladder bile was aspirated completely through a 20-gauge needle inserted obliquely. A serosal purse-string of 5-0 nonabsorbable suture was used to secure closure of the puncture site. The volume of aspirated bile was measured, and aliquots were saved for culture and for determination of phospholipid, choles¬ terol, and bile salt concentrations. The same procedure was re¬ peated 3, 6, 9, and 12 weeks after the initial operation. Dogs in group 2 (proximal gastric vagotomy) had, as their first operation, complete aspiration of the gallbladder, followed by proximal gas¬ tric vagotomy, care being taken to preserve the anterior and posterior nerves of Latarjet. The operative technique has been previously described.5 Gallbladder bile was aspirated during lap¬ arotomies performed at 3, 6, 9, and 12 weeks, as in group 1 dogs. Dogs in group 3 (truncal vagotomy) had complete aspiration of gallbladder bile and transthoracic truncal vagotomy at the first operation. Gallbladder bile was aspirated by additional lap¬ arotomies at 3, 6, 9, and 12 weeks. Dogs in group 4 (truncal vagotomy and pyloroplasty) had com¬ plete aspiration of gallbladder bile, a standard Weinberg modi¬ fication of a Heinecke-Mikulicz pyloroplasty, and transthoracic truncal vagotomy as their first operation. This was followed by as¬ piration of gallbladder bile at additional laparotomies at 3, 6, 9, and 12 weeks. Bile from each operation in each dog in all groups was mea¬ sured, and samples were cultured aerobically and anaerobically and analyzed fpr phospholipid,17 cholesterol,7 and bile acid concen¬ trations." Because of great individual variations in absolute values for the components analyzed, values for samples taken at the ini¬ tial operation were normalized for each dog, and all subsequent measurements were recorded as percent change.
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After completion of the experiments, all dogs were'killed and their gallbladders examined.
RESULTS All dogs survived the experiments. Dogs undergoing truncal vagotomy alone were observed to vomit for eight to ten days after initial operation, followed by slow recov¬ ery. The dogs in the other groups had no detectable vomit¬ ing after the initial procedure. Gallbladder
Aspirate
Volumes
Both sham and proximal gastric vagotomy dogs showed decrease in the volume of gallbladder bile at three weeks (Fig 1). This decrease was significant in the proximal gas¬ tric vagotomy group (P < .05, rank sum). No further sig¬ nificant changes occurred at 6, 9, and 12 weeks. Dogs with truncal vagotomy and truncal vagotomy and pyloroplasty showed marked, significant increases in volume of bile as¬ pirated at three weeks (P < .01 and .05, respectively, rank sum). These findings persisted at 6, 9, and 12 weeks (Fig a
1). Cultures No positive cultures were obtained at initial operation. One dog in the truncal vagotomy and pyloroplasty group had a culture positive for a few streptococci three weeks after initial operation. One dog in the truncal vagotomy group had a culture positive for staphylococci six weeks after initial operation. Nine and 12 weeks after initial op¬ erations, 20 of the 28 cultures were positive (Table 1). Thus, the values for phospholipid, cholesterol, and bile salt concentrations are not presented for these two sample pe¬ riods. Bile
6~ ~9
12 3 WEEKS POSTOPERATION Fig 1 —Effect of various operations on volume of bile aspirated from gallbladder in fasted state. Each point is mean of four mea¬ surements in vagotomized groups and two measurements in sham group. Truncal vagotomy, TV; truncal vagotomy and pyloro¬ plasty, TV+P; proximal gastric vagotomy, PGV. Standard error of mean is indicated. O
concentration was seen in group 4 at three and six weeks. Phospholipid Concentrations.—Dogs in group 1 showed wide variations in phospholipid levels at three weeks, making values in the other groups difficult to interpret in comparison to the sham group (Table 3). Nevertheless, dogs with proximal gastric vagotomies showed minimal variations from their own initial values. The dogs with truncal vagotomies had consistently lower phospholipid levels after operation than before. The dogs with truncal vagotomies and pyloroplasties showed consistently in¬ creased phospholipid levels after operation. Bile Salt Concentrations.—In group 1 dogs, bile acid con-
Composition
Cholesterol Concentration.—Individual and mean percent are shown in Table 2. An increase in cholesterol
changes
Table 1.—Bacterial Cultures of Gallbladder Bile*
Operative Group Group 1 :
Weeks After Initial Operation
Dog No. None None None None
Gram-positive Gram-positive
None
None
None
Staphylococcl,
None None None
None None None
None None
None None Bacillus species,
9 10
None None
None None
Staphylococci None
Staphylococci Bacillus species
11 12
None None None None
None Few streptococci None None
None None None None
Staphylococci Staphylococci Gram-positive cocci Gram-positive cocci
sham
gastric vagotomy
Group 3:
truncal vagotomy
truncal vagotomy and
pyloroplasty '
12
None None None None
Group 2: proximal
Group 4:
9
6
None None None None
13 14
All samples cultured under aerobic and anaerobic conditions for
None
seven
cocci cocci
None None
streptococci
days.
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None
Gram-positive
cocci
None
Gram-positive cocci. Bacillus species Gram-positive cocci None
Staphylococci
Anaerobic
Streptococcus Staphylococci
Bacillus species, Clostridium species Bacillus species
Staphylococci None
Staphylococci
Fig 2.—Left, Gallbladder from dog 8 of truncal vagotomy group, showing multiple stones. Right, Microscopic section of gallblad¬ der wall showing evidence of chronic inflammation. bile
compositions were well within the zone of cholesterol solubility when plotted on the triangular coordinates of Admirand and Small,10 and these observations agree with
centrations were lower after sham operation (Table 4). In dogs with proximal gastric vagotomies, the mean change in bile acid concentration was increased at three and six weeks. This was also found to be true in the dogs with truncal vagotomies. The dogs with truncal vagotomies and pyloroplasties did not show such an increase.
Autopsy At autopsy dogs 8 and 9 of the truncal vagotomy group and dogs 11 and 14 of the truncal vagotomy and pyloro¬ plasty group were found to have stones in their gallblad¬ ders (Fig 2 and 3). No stones were found in the dogs in the sham or proximal gastric vagotomy group.
those of White et al.11 The present data do not clarify the conflicting reports now present in the literature. After selective gastric and truncal vagotomy in dogs with pyloroplasties, Inberg et al12 intermittently sampled bile for one to two weeks through an indwelling gallbladder cannula buried subcu-
Table 2.—Percent Changes in Cholesterol Concentration of Canine Gallbadder Bile Following Operation
Operative Group Group 1: sham
COMMENT In previous studies, truncal vagotomy has been reported to have an unfavorable effect on bile composition in the dog, but no simultaneous comparisons of proximal gastric vagotomy were carried out.' Griffith9 indicated that the in¬ cidence of gallstones in patients after selective gastric va¬ gotomy and antrectomy or pyloroplasty might be lower than in patients with truncal vagotomy and drainage pro¬ cedures. However, there has been no unanimity of data on the effects of various types of vagotomy on the many fac¬ tors that might lead to biliary stone formation. The magnitude of change in the concentrations of the three constituents of bile after any operation in this study was not sufficient to produce definitely lithogenic bile. All
Group 2:
proximal gastric
vagotomy
Dog No. 1 2 X 3 4 5
J X
Group 3:
truncal vagotomy
Group 4:
truncal vagotomy and
pyloroplasty
*
7 8 9 10
X 11 12 13 14
X
Values not averaged into
by bacteria.
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means
Weeks After Initial Operation ,-»-„ 3
+19.5 —19.5 0.0 -39.3 —30.9
+14.6 —40.2 -23.9 +12.9 -24.8 —42.6
+63.7 +2.3 -10.5
+181.3* +72.4 +67.2 +43.2
6 —13.2 —29.3 —21.3
+1.5 +20.5 +54.2 +22.9 +24.7 +15.6 +50.1 —14.6* +83.3 +48.6 +28.7 +35.5 +14.6 —7.3
+17.9
because of contamination of bile
Fig 3—Left, Gallbladder from dog 11 of truncal vagotomy and pyloroplasty group showing multiple stones. Right, Microscopic section of gallbladder wall showing evidence of chronic inflam¬ mation.
taneously. They found no significant change in concentra¬ tions of cholesterol, phospholipids, and bile salts. They did note a wide variability in their control values. These in¬ vestigators did not report bacterial cultures, and the oper¬ ations were carried out sequentially on the same group of four dogs. White et al,11 using a chronic gallbladder fistula in dogs with truncal vagotomy and pyloroplasty, found no significant change in cholesterol concentration, an in-
in phospholipid concentration at six weeks followed by a decrease at five months, and a slight decrease in bile salt concentration. Amdrup and Griffith13 found no change in bile salt, phospholipid, and cholesterol concentrations after various forms of hepatic, celiac, and gastric vagai denervation in dogs. These research groups measured gallbladder bile with crease
some
sham
Dog No. 1
X
+18.5
3 4 5
—25.6
6 0.0 0.0 0.0 -36.6
+7.7 +12.2
+29.3 +17.3
_6
—14.9 -5.2 —33.3 —40.5 —20.9 -8.2 -25.7 +24.6 +78.0* +40.3
—14.1 -1.0 —37.8 —33.9
_2
Group 2: proximal gastric vagotomy
X
Group 3:
truncal vagotomy
Group 4:
truncal vagotomy and
pyloroplasty
7 8 9 10 X 11 12 13 14
X *
Values not averaged into
by bacteria.
Weeks After Initial Operation ,-«-,
means
3 +37.7 —0.7
+45.2 +36.7
Operative Group Group 1: sham
Group 2: proximal gastric vagotomy
Dog No. 1 2 X 3 4 5
J X
Group 3:
truncal vagotomy
—8.0* -48.1 —39.9
Group 4:
+24.6 +13.0 +63.0 +13.9 +28.6
because of contamination of bile
case
of Am-
Table 4.—Percent Changes in Bile Salt Concentrations of Canine Gallbladder Bile Following Operation
Table 3.—Percent Changes in Phospholipid Concentration of Canine Gallbadder Bile Following Operation
Operative Group Group 1:
form of chronic cannulation or, in the
truncal vagotomy and
pyloroplasty
*
7 8 9 10 X 11 12 13 14 X
Values not averaged into
by bacteria.
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means
Weeks After Initial Operation ,-*-, 3 6 -20.5 -29.5 -21.1 —2.0 -20.8 -15.8 —1.9 -3.5 +25.9 +23.3 -7.3 -7.8 +121.5 +151.0 +34.5 +40.7 +149.2 +226.1 +3.6 -39.7 +15.0* —12.3 -36.4 -2.6 +15.2 +75.7 +60.9 -33.8 +3.0* +1.2 +4.9 +13.2 +4.2 —22.0 -8.2 +13.3
because of contamination of bile
and Griffith, by aspiration of bile from canine gall¬ bladders in which human gallstones had been inserted. The possibility of infection of bile in the presence of chronic cannulation must be considered since bacteria may alter the concentration of phospholipids and bile salts. Previous investigators have underscored the prob¬ lems of chronic cannulation in studies of this type.14 Fletcher and Clark15 studied the composition of common duct bile in cholecystectomized dogs before and after truncal vagotomy and pyloroplasty. They used a chronic cannulation system that diverted bile out and then back into the common duct so that specimens could be taken at will with minimal disturbance to the enterohepatic circu¬ lation. Using a fatty meal as a stimulus, they found no changes in cholesterol or phospholipid concentration but a decrease in cholates. Smith et alle performed similar ex¬ periments in patients with duodenal ulcers before and af¬ ter truncal vagotomy and pyloroplasty, cannulating the duodenum perorally and stimulating bile flow with cho¬ lecystokinin. They found the concentrations of cholesterol, phospholipid, and bile salts to be unchanged ten days post¬ operatively, but all were increased one year after the ulcer operation. The relative percent compositions were not dif¬ ferent, however. The above studies cannot be compared to those dealing with gallbladder bile alone because of the unknown contribution of hepatic bile itself. The present studies do demonstrate that proximal gas¬ tric vagotomy in dogs does not lead to an increase in gall¬ bladder volume, whereas both truncal vagotomy alone and with pyloroplasty do increase the volume of the gallblad¬ der, as measured by aspirations over a period of three months. These findings support the indirect cholecystographic measurements made by Amberg et al17 in dogs and Parkin et alls and Inberg and Vuoria19 in humans, but are in contrast to previous studies in this laboratory in which gallbladder volume was estimated from single plane cholangiograms and unidirectional caliper measure¬ ments with dogs under anesthesia.1 For an animal species that rarely forms gallstones, it was surprising to find that half of those dogs with truncal vagotomies or truncal vagotomies and pyloroplasties had gallbladder stones at autopsy. No dogs in the sham or proximal gastric vagotomy group formed gallstones. It is possible that infection of the bile toward the end of the experiment was responsible, but if this were the only fac¬ tor, the sham and proximal gastric vagotomy dogs, which also had infected bile, should have had stones also (Table
drup
1).
The finding of stones in many of our dogs with enlarged gallbladders supports the thesis that decreased motility of the gallbladder after vagai denervation, in conjunction with alterations in the composition of gallbladder bile, is a major factor in the production of cholelithiasis. If this as¬ sumption proves to be correct, then proximal gastric va¬ gotomy may be valuable in preventing the postoperative tendency to cholelithiasis. Proof or denial of this suppo¬ sition awaits the repetition of this type of study in an ani¬ mal preparation with bile composition more analogous to
the human.
This investigation was supported by grants from the John A. Hartford Foundation Ine and the UCLA Department of Surgery Education and Re¬ search Fund.
References 1. Tompkins RK, Kraft AR, Zimmerman BA, et al: Clinical and biochemical evidence of increased gallstone formation after complete vagotomy. Surgery 71:196-200, 1972. 2. Clave RA, Gaspar MR: Incidence of gallbladder disease after vagotomy. Am J Surg 118:169-176, 1969. 3. Miller MC: Cholelithiasis developing after vagotomy. Can Med Assoc J 98:350-354, 1968. 4. Nobles ER: Vagotomy and gastroenterostomy: Fifteen-year follow-up of 175 patients. Am Surg 32:177-182, 1966. 5. WilburBG, Kelly KA: Effect of proximal gastric, complete gastric, and truncal vagotomy on canine gastric electrical activity and emptying of liquids and solids. Ann Surg 178:295-303, 1973. 6.Lowry OH, Roberts NR, Leiner KY, et al: The quantitative histochemistry of brain: I. Chemical methods. J Biol Chem 207:1-18, 1954. 7. Abell LL, Levy BB, Brodie BB, et al: A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem 195:357-366, 1952. 8. Talalay P: Enzymatic analysis of steroid hormones. Methods Biochem Anal 8:119-143, 1960. 9. Griffith CA: Significant functions of thehepatic and celiac vagi. Am J Surg 118:251-259, 1969. 10. Admirand WH, Small DM: The physiochemical basis of cholesterol gallstone formation in man. J Clin Invest 47:1043-1052, 1968. 11. White TT, Tournut RA, Scharplatx D, et al: The effect of vagotomy on biliary secretions and bile salt pools in dogs. Ann Surg 179:406-411,1974. 12. Inberg MV, Ahonen J, Scheinin TM: Bile composition in the canine gallbladder after selective gastric and truncal vagotomy. Ann Chir Gynaecol Fenn 58:329-333, 1969. The effects of vagotomy upon biliary func13. Amdrup BM, GriffithCA: tion in dogs. J Surg Res 10:209-212, 1970. 14. IsazaJ, Jones DT, Dragstedt LR, et al: The effect of vagotomy on motor function of the gallbladder. Surgery 70:616-621, 1971. 15. Fletcher DM, Clark CG: Changes in canine bile flow and composition after vagotomy. Br J Surg 56:103-106, 1969. 16. Smith DC, MacKay C, McAllister RA: The effect of vagotomy and 18:1973. 65, drainage on the composition of bile. Scott Med J 17. Amberg JR, JonesRS, Moss A, et al: Effect of vagotomy on gallbladder size and contractility in the dog. InRadiol vest 8:371-376, 1973. 18. Parkin GJS, Smith RB, Johnston D: Gallbladder volume and contractility after truncal, selective and highly selective (parietal-cell) vagotomy in man. Ann Surg 178:581-586, 1973. 19. Inberg MV, Vuoria M: Human gallbladder function after selective gastric and total abdominal vagotomy. Acta Chir Scand 135:625-633,1969.
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Wilbur, MD; Francisco C. Gomez, MD; Ronald K. Tompkins,
Three groups of four dogs each underwent proximal gastric vagotomy, truncal vagotomy, or truncal vagotomy with pyloroplasty. Two dogs had sham operations. Gallbladder bile was aspirated and measured. Aliquots were cultured and assayed for cholesterol, phospholipid, and bile salts initially and at subsequent laparotomies. Both truncal vagotomy groups showed marked increases in aspirate volume at subsequent laparotomies. The sham and proximal gastric vagotomy groups showed a small initial decrease in mean aspirate volume without further significant changes. When the bile assay data were plotted on triangular coordinates, all points for all groups remained well within the area of cholesterol solubility. Nevertheless, two dogs in each truncal vagotomy group were found to have gallstones. No stones were found in the sham and proximal gastric vagotomy groups. Proximal gastric vagotomy appears to preserve fasting gallbladder bile volume and does not alter bile composition in the dog.
reported vagotomy Truncal tendency cholelithiasis has been
to increase the in man.14 Alterations in motility of the biliary tract and increases in the lithogenicity of bile are mechanisms by which vagotomy may predispose to an increased rate of gallstone formation. Little evidence has been presented concerning the effect of proximal gastric vagotomy on the composition and vol¬ ume of gallbladder bile. The present study was designed to compare effects of proximal gastric vagotomy, truncal vagotomy, and truncal vagotomy and pyloroplasty on the volume and composition of gallbladder bile in dogs.
to
Accepted
for publication March 7, 1975. From the Biliary Lipid Laboratory, Department of Surgery, UCLA School of Medicine, Los Angeles. Read before the annual meeting of the Southern California Chapter of the American College of Surgeons, Santa Barbara, Calif, Jan 17, 1975. Reprint requests to Biliary Lipid Laboratory, Department of Surgery, UCLA School of Medicine, Los Angeles, CA 90024 (Drs. Wilbur and Tomp-
kins).
MD
METHODS Fourteen adult mongrel dogs weighing 10 to 15 kg comprised the study group. Two dogs that underwent sham operations with aspiration of the gallbladder served as longitudinal controls (group 1). Twelve dogs were divided into three groups (groups 2,3, and 4) of four dogs each. Dogs in group 1 were operated on after an 18-hour fast, and the gallbladder bile was aspirated completely through a 20-gauge needle inserted obliquely. A serosal purse-string of 5-0 nonabsorbable suture was used to secure closure of the puncture site. The volume of aspirated bile was measured, and aliquots were saved for culture and for determination of phospholipid, choles¬ terol, and bile salt concentrations. The same procedure was re¬ peated 3, 6, 9, and 12 weeks after the initial operation. Dogs in group 2 (proximal gastric vagotomy) had, as their first operation, complete aspiration of the gallbladder, followed by proximal gas¬ tric vagotomy, care being taken to preserve the anterior and posterior nerves of Latarjet. The operative technique has been previously described.5 Gallbladder bile was aspirated during lap¬ arotomies performed at 3, 6, 9, and 12 weeks, as in group 1 dogs. Dogs in group 3 (truncal vagotomy) had complete aspiration of gallbladder bile and transthoracic truncal vagotomy at the first operation. Gallbladder bile was aspirated by additional lap¬ arotomies at 3, 6, 9, and 12 weeks. Dogs in group 4 (truncal vagotomy and pyloroplasty) had com¬ plete aspiration of gallbladder bile, a standard Weinberg modi¬ fication of a Heinecke-Mikulicz pyloroplasty, and transthoracic truncal vagotomy as their first operation. This was followed by as¬ piration of gallbladder bile at additional laparotomies at 3, 6, 9, and 12 weeks. Bile from each operation in each dog in all groups was mea¬ sured, and samples were cultured aerobically and anaerobically and analyzed fpr phospholipid,17 cholesterol,7 and bile acid concen¬ trations." Because of great individual variations in absolute values for the components analyzed, values for samples taken at the ini¬ tial operation were normalized for each dog, and all subsequent measurements were recorded as percent change.
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After completion of the experiments, all dogs were'killed and their gallbladders examined.
RESULTS All dogs survived the experiments. Dogs undergoing truncal vagotomy alone were observed to vomit for eight to ten days after initial operation, followed by slow recov¬ ery. The dogs in the other groups had no detectable vomit¬ ing after the initial procedure. Gallbladder
Aspirate
Volumes
Both sham and proximal gastric vagotomy dogs showed decrease in the volume of gallbladder bile at three weeks (Fig 1). This decrease was significant in the proximal gas¬ tric vagotomy group (P < .05, rank sum). No further sig¬ nificant changes occurred at 6, 9, and 12 weeks. Dogs with truncal vagotomy and truncal vagotomy and pyloroplasty showed marked, significant increases in volume of bile as¬ pirated at three weeks (P < .01 and .05, respectively, rank sum). These findings persisted at 6, 9, and 12 weeks (Fig a
1). Cultures No positive cultures were obtained at initial operation. One dog in the truncal vagotomy and pyloroplasty group had a culture positive for a few streptococci three weeks after initial operation. One dog in the truncal vagotomy group had a culture positive for staphylococci six weeks after initial operation. Nine and 12 weeks after initial op¬ erations, 20 of the 28 cultures were positive (Table 1). Thus, the values for phospholipid, cholesterol, and bile salt concentrations are not presented for these two sample pe¬ riods. Bile
6~ ~9
12 3 WEEKS POSTOPERATION Fig 1 —Effect of various operations on volume of bile aspirated from gallbladder in fasted state. Each point is mean of four mea¬ surements in vagotomized groups and two measurements in sham group. Truncal vagotomy, TV; truncal vagotomy and pyloro¬ plasty, TV+P; proximal gastric vagotomy, PGV. Standard error of mean is indicated. O
concentration was seen in group 4 at three and six weeks. Phospholipid Concentrations.—Dogs in group 1 showed wide variations in phospholipid levels at three weeks, making values in the other groups difficult to interpret in comparison to the sham group (Table 3). Nevertheless, dogs with proximal gastric vagotomies showed minimal variations from their own initial values. The dogs with truncal vagotomies had consistently lower phospholipid levels after operation than before. The dogs with truncal vagotomies and pyloroplasties showed consistently in¬ creased phospholipid levels after operation. Bile Salt Concentrations.—In group 1 dogs, bile acid con-
Composition
Cholesterol Concentration.—Individual and mean percent are shown in Table 2. An increase in cholesterol
changes
Table 1.—Bacterial Cultures of Gallbladder Bile*
Operative Group Group 1 :
Weeks After Initial Operation
Dog No. None None None None
Gram-positive Gram-positive
None
None
None
Staphylococcl,
None None None
None None None
None None
None None Bacillus species,
9 10
None None
None None
Staphylococci None
Staphylococci Bacillus species
11 12
None None None None
None Few streptococci None None
None None None None
Staphylococci Staphylococci Gram-positive cocci Gram-positive cocci
sham
gastric vagotomy
Group 3:
truncal vagotomy
truncal vagotomy and
pyloroplasty '
12
None None None None
Group 2: proximal
Group 4:
9
6
None None None None
13 14
All samples cultured under aerobic and anaerobic conditions for
None
seven
cocci cocci
None None
streptococci
days.
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None
Gram-positive
cocci
None
Gram-positive cocci. Bacillus species Gram-positive cocci None
Staphylococci
Anaerobic
Streptococcus Staphylococci
Bacillus species, Clostridium species Bacillus species
Staphylococci None
Staphylococci
Fig 2.—Left, Gallbladder from dog 8 of truncal vagotomy group, showing multiple stones. Right, Microscopic section of gallblad¬ der wall showing evidence of chronic inflammation. bile
compositions were well within the zone of cholesterol solubility when plotted on the triangular coordinates of Admirand and Small,10 and these observations agree with
centrations were lower after sham operation (Table 4). In dogs with proximal gastric vagotomies, the mean change in bile acid concentration was increased at three and six weeks. This was also found to be true in the dogs with truncal vagotomies. The dogs with truncal vagotomies and pyloroplasties did not show such an increase.
Autopsy At autopsy dogs 8 and 9 of the truncal vagotomy group and dogs 11 and 14 of the truncal vagotomy and pyloro¬ plasty group were found to have stones in their gallblad¬ ders (Fig 2 and 3). No stones were found in the dogs in the sham or proximal gastric vagotomy group.
those of White et al.11 The present data do not clarify the conflicting reports now present in the literature. After selective gastric and truncal vagotomy in dogs with pyloroplasties, Inberg et al12 intermittently sampled bile for one to two weeks through an indwelling gallbladder cannula buried subcu-
Table 2.—Percent Changes in Cholesterol Concentration of Canine Gallbadder Bile Following Operation
Operative Group Group 1: sham
COMMENT In previous studies, truncal vagotomy has been reported to have an unfavorable effect on bile composition in the dog, but no simultaneous comparisons of proximal gastric vagotomy were carried out.' Griffith9 indicated that the in¬ cidence of gallstones in patients after selective gastric va¬ gotomy and antrectomy or pyloroplasty might be lower than in patients with truncal vagotomy and drainage pro¬ cedures. However, there has been no unanimity of data on the effects of various types of vagotomy on the many fac¬ tors that might lead to biliary stone formation. The magnitude of change in the concentrations of the three constituents of bile after any operation in this study was not sufficient to produce definitely lithogenic bile. All
Group 2:
proximal gastric
vagotomy
Dog No. 1 2 X 3 4 5
J X
Group 3:
truncal vagotomy
Group 4:
truncal vagotomy and
pyloroplasty
*
7 8 9 10
X 11 12 13 14
X
Values not averaged into
by bacteria.
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means
Weeks After Initial Operation ,-»-„ 3
+19.5 —19.5 0.0 -39.3 —30.9
+14.6 —40.2 -23.9 +12.9 -24.8 —42.6
+63.7 +2.3 -10.5
+181.3* +72.4 +67.2 +43.2
6 —13.2 —29.3 —21.3
+1.5 +20.5 +54.2 +22.9 +24.7 +15.6 +50.1 —14.6* +83.3 +48.6 +28.7 +35.5 +14.6 —7.3
+17.9
because of contamination of bile
Fig 3—Left, Gallbladder from dog 11 of truncal vagotomy and pyloroplasty group showing multiple stones. Right, Microscopic section of gallbladder wall showing evidence of chronic inflam¬ mation.
taneously. They found no significant change in concentra¬ tions of cholesterol, phospholipids, and bile salts. They did note a wide variability in their control values. These in¬ vestigators did not report bacterial cultures, and the oper¬ ations were carried out sequentially on the same group of four dogs. White et al,11 using a chronic gallbladder fistula in dogs with truncal vagotomy and pyloroplasty, found no significant change in cholesterol concentration, an in-
in phospholipid concentration at six weeks followed by a decrease at five months, and a slight decrease in bile salt concentration. Amdrup and Griffith13 found no change in bile salt, phospholipid, and cholesterol concentrations after various forms of hepatic, celiac, and gastric vagai denervation in dogs. These research groups measured gallbladder bile with crease
some
sham
Dog No. 1
X
+18.5
3 4 5
—25.6
6 0.0 0.0 0.0 -36.6
+7.7 +12.2
+29.3 +17.3
_6
—14.9 -5.2 —33.3 —40.5 —20.9 -8.2 -25.7 +24.6 +78.0* +40.3
—14.1 -1.0 —37.8 —33.9
_2
Group 2: proximal gastric vagotomy
X
Group 3:
truncal vagotomy
Group 4:
truncal vagotomy and
pyloroplasty
7 8 9 10 X 11 12 13 14
X *
Values not averaged into
by bacteria.
Weeks After Initial Operation ,-«-,
means
3 +37.7 —0.7
+45.2 +36.7
Operative Group Group 1: sham
Group 2: proximal gastric vagotomy
Dog No. 1 2 X 3 4 5
J X
Group 3:
truncal vagotomy
—8.0* -48.1 —39.9
Group 4:
+24.6 +13.0 +63.0 +13.9 +28.6
because of contamination of bile
case
of Am-
Table 4.—Percent Changes in Bile Salt Concentrations of Canine Gallbladder Bile Following Operation
Table 3.—Percent Changes in Phospholipid Concentration of Canine Gallbadder Bile Following Operation
Operative Group Group 1:
form of chronic cannulation or, in the
truncal vagotomy and
pyloroplasty
*
7 8 9 10 X 11 12 13 14 X
Values not averaged into
by bacteria.
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means
Weeks After Initial Operation ,-*-, 3 6 -20.5 -29.5 -21.1 —2.0 -20.8 -15.8 —1.9 -3.5 +25.9 +23.3 -7.3 -7.8 +121.5 +151.0 +34.5 +40.7 +149.2 +226.1 +3.6 -39.7 +15.0* —12.3 -36.4 -2.6 +15.2 +75.7 +60.9 -33.8 +3.0* +1.2 +4.9 +13.2 +4.2 —22.0 -8.2 +13.3
because of contamination of bile
and Griffith, by aspiration of bile from canine gall¬ bladders in which human gallstones had been inserted. The possibility of infection of bile in the presence of chronic cannulation must be considered since bacteria may alter the concentration of phospholipids and bile salts. Previous investigators have underscored the prob¬ lems of chronic cannulation in studies of this type.14 Fletcher and Clark15 studied the composition of common duct bile in cholecystectomized dogs before and after truncal vagotomy and pyloroplasty. They used a chronic cannulation system that diverted bile out and then back into the common duct so that specimens could be taken at will with minimal disturbance to the enterohepatic circu¬ lation. Using a fatty meal as a stimulus, they found no changes in cholesterol or phospholipid concentration but a decrease in cholates. Smith et alle performed similar ex¬ periments in patients with duodenal ulcers before and af¬ ter truncal vagotomy and pyloroplasty, cannulating the duodenum perorally and stimulating bile flow with cho¬ lecystokinin. They found the concentrations of cholesterol, phospholipid, and bile salts to be unchanged ten days post¬ operatively, but all were increased one year after the ulcer operation. The relative percent compositions were not dif¬ ferent, however. The above studies cannot be compared to those dealing with gallbladder bile alone because of the unknown contribution of hepatic bile itself. The present studies do demonstrate that proximal gas¬ tric vagotomy in dogs does not lead to an increase in gall¬ bladder volume, whereas both truncal vagotomy alone and with pyloroplasty do increase the volume of the gallblad¬ der, as measured by aspirations over a period of three months. These findings support the indirect cholecystographic measurements made by Amberg et al17 in dogs and Parkin et alls and Inberg and Vuoria19 in humans, but are in contrast to previous studies in this laboratory in which gallbladder volume was estimated from single plane cholangiograms and unidirectional caliper measure¬ ments with dogs under anesthesia.1 For an animal species that rarely forms gallstones, it was surprising to find that half of those dogs with truncal vagotomies or truncal vagotomies and pyloroplasties had gallbladder stones at autopsy. No dogs in the sham or proximal gastric vagotomy group formed gallstones. It is possible that infection of the bile toward the end of the experiment was responsible, but if this were the only fac¬ tor, the sham and proximal gastric vagotomy dogs, which also had infected bile, should have had stones also (Table
drup
1).
The finding of stones in many of our dogs with enlarged gallbladders supports the thesis that decreased motility of the gallbladder after vagai denervation, in conjunction with alterations in the composition of gallbladder bile, is a major factor in the production of cholelithiasis. If this as¬ sumption proves to be correct, then proximal gastric va¬ gotomy may be valuable in preventing the postoperative tendency to cholelithiasis. Proof or denial of this suppo¬ sition awaits the repetition of this type of study in an ani¬ mal preparation with bile composition more analogous to
the human.
This investigation was supported by grants from the John A. Hartford Foundation Ine and the UCLA Department of Surgery Education and Re¬ search Fund.
References 1. Tompkins RK, Kraft AR, Zimmerman BA, et al: Clinical and biochemical evidence of increased gallstone formation after complete vagotomy. Surgery 71:196-200, 1972. 2. Clave RA, Gaspar MR: Incidence of gallbladder disease after vagotomy. Am J Surg 118:169-176, 1969. 3. Miller MC: Cholelithiasis developing after vagotomy. Can Med Assoc J 98:350-354, 1968. 4. Nobles ER: Vagotomy and gastroenterostomy: Fifteen-year follow-up of 175 patients. Am Surg 32:177-182, 1966. 5. WilburBG, Kelly KA: Effect of proximal gastric, complete gastric, and truncal vagotomy on canine gastric electrical activity and emptying of liquids and solids. Ann Surg 178:295-303, 1973. 6.Lowry OH, Roberts NR, Leiner KY, et al: The quantitative histochemistry of brain: I. Chemical methods. J Biol Chem 207:1-18, 1954. 7. Abell LL, Levy BB, Brodie BB, et al: A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem 195:357-366, 1952. 8. Talalay P: Enzymatic analysis of steroid hormones. Methods Biochem Anal 8:119-143, 1960. 9. Griffith CA: Significant functions of thehepatic and celiac vagi. Am J Surg 118:251-259, 1969. 10. Admirand WH, Small DM: The physiochemical basis of cholesterol gallstone formation in man. J Clin Invest 47:1043-1052, 1968. 11. White TT, Tournut RA, Scharplatx D, et al: The effect of vagotomy on biliary secretions and bile salt pools in dogs. Ann Surg 179:406-411,1974. 12. Inberg MV, Ahonen J, Scheinin TM: Bile composition in the canine gallbladder after selective gastric and truncal vagotomy. Ann Chir Gynaecol Fenn 58:329-333, 1969. The effects of vagotomy upon biliary func13. Amdrup BM, GriffithCA: tion in dogs. J Surg Res 10:209-212, 1970. 14. IsazaJ, Jones DT, Dragstedt LR, et al: The effect of vagotomy on motor function of the gallbladder. Surgery 70:616-621, 1971. 15. Fletcher DM, Clark CG: Changes in canine bile flow and composition after vagotomy. Br J Surg 56:103-106, 1969. 16. Smith DC, MacKay C, McAllister RA: The effect of vagotomy and 18:1973. 65, drainage on the composition of bile. Scott Med J 17. Amberg JR, JonesRS, Moss A, et al: Effect of vagotomy on gallbladder size and contractility in the dog. InRadiol vest 8:371-376, 1973. 18. Parkin GJS, Smith RB, Johnston D: Gallbladder volume and contractility after truncal, selective and highly selective (parietal-cell) vagotomy in man. Ann Surg 178:581-586, 1973. 19. Inberg MV, Vuoria M: Human gallbladder function after selective gastric and total abdominal vagotomy. Acta Chir Scand 135:625-633,1969.
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