The insulin response of vagally innervated gastric pouches following selective gastric vagotomy

THE

INSULIN GASTRIC

RESPONSE POUCHES GASTRIC

GEOFFREY

OF VAGALLY FOLLOWING VAGOTOMY

PRITCHARD,

CHARLES

A. HENRY

M.B.,

GRIFFITH, N.

HARKINS,

IN previous investigations for the completeness of gastric vagotomy by the selective technique the results of insulin tests were negative in both dogs [5] and man [4]. However, the method for collection of gastric juice in these earlier investigations [5] was by intubation of the intact stomach and therefore did not eliminate the possibility of contamination of the gastric specimens by neutralizing saliva and duodenal reflux. In view of the fact that the completeness of selective gastric vagotomy continues to be questioned, the present investigation was undertaken with gastric pouches, excluded from the main stomach.

MATERIALS

AND

METHODS

Four mongrel dogs ranging in weight from 12.2 to 16.3 kg. were studied. Each dog was From the Department of Surgery and the First Surgical Service of the University Hospital, University of Washington School of Medicine, Seattle, Wash. This study was aided in part by funds accruing from National Institutes of Health Grant AM-08094. *Visiting Scientist. On leave as an Honorary Associate Surgeon from the Prince Henry Hospital, Syclney, Australia. Submitted for publication Feb. 14, 1967.

68

INNERVATED SELECTIVE

F.R.A.C.S.,” M.D.,

AND

M.D.

provided with a vagally innervated gastric pouch and pyloroplasty. Secretions from the pouches were obtained after stimulation by histamine and insulin. Selective gastric vagotomy was then performed and the histamine and insulin tests repeated,

OPERATIVE

Vagally Innervated Pyloroplasty

TECHNIQUES

Gastric Pouch Plus

The gastric pouches were constructed from the greater curve proximal to the antrum by the technique of Gregory et al. [3]. Vagal innervation to the pouches was kept intact by preserving the seromuscular layer. The pouches were separated from the main stomach by a mucosal bridge using two parallel rows of continuous chromic catgut suture. Drainage from the pouches was provided by stainless steel and nylon cannulae. The pyloroplasties were of the Heinecke-Mikulicz type, modified by Weinberg’s technique of a single layer of interrupted silk sutures. In performing the pyloroplasties particular care was taken to avoid manipulation and traction of the greater and lesser omenta SO as not to disturb

PRITCHARD

ET

AL.:

THE

INSULIN

any innervation within the omenta to the antrum and pylorus (Fig. 1, Stage I). The dogs were allowed to recover for one month, after which the intact state of the sutured mucosal bridges was tested by oral feeding of methylene blue. Complete exclusion of pouch from stomach was verified in 4 dogs. A fifth dog with a demonstrated fistula through the mucosal bridge was discarded from the study. Selectizje Gastric

Vagotomy

All gastric vagal fibers were transected at the gastric cardia. The anatomical and physiological integrity of the hepatic and celiac vagi was preserved by carefully avoiding their transection and minimizing their manipulation and traction (Fig. 1, Stage II).

SECRETORY

STUDIES

The insulin and histamine tests were performed after a postoperative recovery of at least one month. Before each test the dogs were fasted for a minimum of 18 hours. All tests were conducted in a Pavlov stand, to which the dogs had previously been trained. No more than three tests per week were performed upon each dog. Insulin

Tests

Secretions from the pouch were collected at half-hourly intervals. When the halfrate was less than 1 hourly secretory

RESPONSE

STAGE II

Fig. 1. Operative Procedures. Stage I: Vagally pouch and pyloroplasty. innervated gastric Stage II: Selective gastric vagotomy.

VAGALLY

INNERVATED

GASTRIC

POUCHES

milliliter, regular bovine insulin was administered intravenously in a dosage of 0.5 unit per kilogram of body weight. After the injection of insulin secretions were collected at half-hourly intervals for 4 hours. Samples of venous blood were taken before, and at one-half and at 1 hour after the injection of insulin, The concentration of true glucose in each sample was estimated by an enzymatic method [ 81. Three tests were performed upon each dog before vagotomy. A positive secretory response was obtained in all preoperative tests, and the concentration of glucose decreased approximately 50%. In the tests after vagotomy the criterion for adequacy of hypoglycemia was set at a decrease in concentration of glucose equal to or greater than the decrease in the tests upon the same dogs before vagotomy. With this criterion five tests were rejected because of an inadequate fall in concentration of true glucose. Left for consideration were three acceptable tests on each dog after vagotomy. Maximal

Histamine

Tests

The dosage of histamine required for a maximal secretory response by each animal was determined before vagotomy as follows: An intravenous infusion of 0.2 mg. of histamine per hour was commenced, and the pouch secretions were collected at 15 minute intervals thereafter. Every 75 minutes the dosage of histamine was doubled until a maximum of 3.2 mg. per hour had been given. The minimal dosage that caused the maximal secretory response was then used for the maximal histamine tests. The maximal histamine tests were conducted by collecting the pouch secretions at half-hourly intervals for 1 hour after a constant plateau of secretion had been attained. Six tests were performed on each dog-three before and three after vagotomy. Gastric

STAGE I

OF

Analysis

The gastric juice was collected by gravity drainage through the cannulas into graduated tubes, and the volume of each specimen was recorded. The specimens were ti-

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trated against 0.1 N NaOH to pH 7 with the Fisher titrimeter. The milliequivalents of total acid in each specimen were then calculated for the results.

RESULTS INSULIN

TESTS

Results of the insulin tests before and after selective gastric vagotomy are presented in Figure 2. Numerical values of the amounts of acid and concentrations of true glucose for each test are presented in Table 1. All secretory responses before vagotomy were and, as seen in unequivocally positive Table 1, notably reproducible. All secretory responses after vagotomy were unequivocally negative. MAXIMAL

HISTAMINE

TESTS

The results for each dog are presented in Figure 3. No significant change in the secretory capacity of the pouches occurred after vagotomy. Before

After

I

1 0 20 G F IO

2127

I 0

L 0

\ I

-1-

l-

2 3 4 o Time in hours following

I 2 insulin

1968 DISCUSSION

In dogs, unlike man, the maximal response of acid to histamine is not significantly changed by complete gastric vagotomy [6, 71. The maximal histamine test in dogs therefore permits a valid comparison of the secretory capacity of gastric pouches before and after vagotomy. In this study the results for the secretory capacity of the gastric pouches before and after vagotomy are relatively equal. Therefore, the results of the insulin tests indicate complete vagotomy of the stomach rather than decreased secretory capacity of the stomach consequent to deterioration of the experimental animals. The completeness of selective gastric vagotomy has been and is questioned on the basis of residual innervation from some hepatic vagal fibers to the pylorus and most distal antrum (Fig. l), and also on the possibility of residual innervation from the celiac vagal division via circuitous pathways from the celiac autonomic plexus. This question primarily concerns the possibility of residual antral innervation and consequently a persistent mechanism for the vagal release of gastrin. The negative results of the insulin tests in this study indicate that neither the hepatic nor the celiac vagi contribute any efferent secretory fibers to the parietal cell mass for a direct vagal response or to the antrum for an indirect vagal response. These results support previous evidence derived from studies concerning motility of the $‘O”-

T Before

TAfter

%

T

P _ 2 h 2 -Q so‘h e 2 s B 3

:t --

The total acid output of the innervated gastric pouches in responseto insulin before and after selective gastric vagotomy. Each graph representsthe mean of three tests. The standard deviation is also indicated.

0

Fig. 2.

Dog no

I

1

i

I

I

4 2105

ri -:

--

f

I

I

I

I

I

I

I

i

(

I

I

1

I I

: I I I

2124

2125

2127

The maximal histamine response before and after selective gastric vagotomy. Each column shows the mean secretion and standard deviation of three tests. Fig. 3.

PRITCHARD

ET

AL.:

THE

INSULIN

Table 1.

Dog No. 2105 Before

After 2124 Before

After 2125 Before

After 2127 Before

After

RESPONSE

Results

of

OF

VAGALLY

INNERVATED

GASTRIC

POUCHES

Insulin Tests

Test

4-Hour Total Acid Output (mEq.)

0

1 2 3

4.16 4.58 4.66

38 37

1 2 3

0.02 0.00 0.10

50

1 2 3

Blood Glucose (mg. % ) After Insulin (min.) 30

23

20 20

:i

24 30 24

24 26 10

7.43 6.54 6.72

43 37

28 27

23 23

1 2 3

0.14 0.01 0.00

51

24 19 24

23 23 30

1 2 3

2.61 2.29 1.90

39 50

18 29

17 24

1 2 3

0.00 0.20 0.00

42 46 43

29 21 21

20 20 20

1 2 3

5.16 5.69 5.77

44 43 35

27 18 23

26 24 22

1 2 3

0.00 0.05 0.02

ii

26 26 26

23 30 33

stomach as follows: First, selective gastric vagotomy without a drainage procedure results in as much gastric stasis as truncal vagotomy without drainage [ 51. Second, electrical stimulation of the canine hepatic and celiac vagi does not elicit a contractile response in the antrum [lo]; a contractile response of the antrum may be elicited only by stimulation of the gastric vagal fibers that course down the lesser curve to the antrum [ 111. In view of the fact that the gross anatomical distribution of the abdominal vagi in man is similar to that in dogs [9], the result of selective gastric vagotomy in man is expected to be the same as in dogs. The evidence in man is as follows: First, selective gastric

ii

54

28

60

vagotomy without a drainage procedure results in severe gastric stasis [2 3. Second, electrical stimulation of the hepatic and celiac vagi does not elicit a contractile response of the stomach [l]. Third, insulin tests after selective gastric vagotomy are consistently negative [4]. On the basis of the foregoing observations, all evidence indicates that neither the hepatic nor celiac vagal divisions contribute any efferent secretory or efferent motor fibers to the stomach. In view of this evidence the function of those hepatic vagal fibers that are readily seen in gross anatomical dissection coursing directly to the pylorus and the most distal antrum remains unknown. Their function may be sensory; or, if efferent motor

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or efferent secretory, it is not demonstrated by the current methods of investigation and may well be insignificant,

insulin test selective preservation of both vagi results in comvagal denervation of

1. 2.

Burge, H. Vagotomy. Wilkins, 19F4. Franksson, C. Selective

72

5.

7.

9. Williams

&

abdominal vagotomy. 1948. Gregory, R. A., Hallenbeck, G. A., and Code, C. F. A modification of the method of Hollander and Jem:rin for making Pavlov pouches. Proc. Sot. Exp. Riol. Med. 49:400, 1942.

Actu Chir. &and. 3.

Baltimore:

C. A. Completeness of gastric vaby the selective technic. Amer. J. Dig. Dis. 12:333, 1967. Griffith, C. A., and Harkins, H. N. Partial gastric vagotomy: An experimental study. Castroenterology 32:96, 1957. Heathcote, B. V., Daly, D. W., and Gillespie, I. E. Secretory responses before and after vagal denervation of a gastric pouch. Gastrocnterology 48~463, 1965. Hood, R. T., Jr., and Code, C. F. Some effects of vagotomy on gastric secretion as studied in dogs with gastric pouches. Surg. Forum 2:73, 1950. Keston, A. S. Glucose (Enzymatic). In D. Seligson (Ed.), Stundurd fvfethods of Clinical Chemistry. New York: Academic, 1963. Vol. 4. P. 101. McCrea, E. D’A. The abdominal distribution of the vagus. J. Anat. 59:18, 1924. Stavney, L. S., Kato, T., Griffith, C. A., Nyhus, L. M., and Harkins, H. N. A physiological study of motility changes following selective gastric vagotomy. J. Surg. Res. 3:390, 1963. Wohlrabe, D. E., and Kelly, W. D. Motility studies of isolated antral pouches before and after vagus denervation. .I. Appl. Physiol. 14:22, 1959. gotomy

8.

REFERENCES

1968

4. Griffith,

G.

CONCLUSION As indicated by the gastric vagotomy with the hepatic and celiac plete efferent secretory the stomach.

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96:409,

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