The Effect of Secretin on Gastric Emptying in Man

Vol. 60, No.3 Printed in U. S. A.

G ASTROENTEROLOGY

Copyright

~

1971 by The Williams & Wilkins Co.

THE EFFECT OF SECRETIN ON GASTRIC EMPTYING IN MAN MONIQUE VAGNE, M.D., AND CLAUDE ANDRE, M.D.

Unite de Recherches de Physio-Pathologie Digestive, lnstitut National de La Sante et de La Recherche M edicale, Lyon, France

Gastric emptying of water was measured in 2 subjects during continuous intravenous infusion of saline and three different doses of secretin. The volume of water remaining in the stomach 20 min after ingestion increased with increasing doses of secretin. Delayed gastric emptying was observed with doses of secretin which are less than maximal for pancreatic secretion. Secretin inhibition of gastric acid secretion could not account for the results. Therefore, it is concluded that secretin could playa physiological role in slowing gastric emptying. This effect, like other actions of the hormone, would tend to prevent excessive acidification of the duodenum. Chey et al. l showed that secretin modifies human gastric emptying. In their study, however, only one dose of secretin was given intravenously as a single injection, and one could not be certain whether the observed effect was pharmacological, i.e., produced by a quantity of secretin greater than that which can be released in vivo. We determined a dose-response curve in 2 healthy subjects with continuous infusions of secretin and tried to assess the role of gastric acid inhibition in this mechanism.

Methods Both authors served as subjects and had been fasting for about 12 hr before the experiments. A gastric tube was placed in the gastric antrum under fluoroscopic observation. Saliva was expectorated continuously. Two consecutive tests were made on the same day using the techniques described by Hunt. 2 After a gastric washout with 250 ml of water, 750 ml of distilled water containing 1.25 g per Received April 14, 1970. Accepted June 22, 1970. Address requests for reprints to: Dr. Monique Vagne, Unite de Recherches de Physio-Pathologie Digestive, Institut National de la Sante et de la Recherche Medicale, Lyon 3", France. The authors are grateful to M. B. Bererd, M. Chantelot, and H. Guiguet for expert technical assistance.

liter of phenol red were given in approximately 2 min. The gastric contents were aspirated after an interval of 20 min and the completeness of the recovery was checked by another washout of 250 ml. The second test was performed after an interval of 10 min under the same conditions. During the first test, a continuous intravenous infusion of 0.15 M NaCI was given with a peristaltic pump (Harvard Apparatus) at a rate of 160 ml per hr. An intravenous infusion of saline or secretin was given randomly 10 min before the second test and was continued until the test was completed. Secretin was purchased at the Gastrointestinal Hormone Unit, Karolinska Institutet, Stockholm, Sweden (batch 16861) and given at doses of 0.125, 0.395, and 1.250 U per kg per hr. Four experiments were performed, two in each subject. The volume of gastric contents was recorded and phenol red concentration was determined with a spectrophotometer at 555 nm (Beckman DB). The pH was evaluated and acidity concentration measured by titrating 5 ml of gastric juice with 0.1 N NaOH to pH 7 using a glass electrode and an automatic burette and pH meter (Methrom). The results were calculated according to Hunt's method. 2 The ratio of concentration of phenol red in the gastric contents recovered (CA) and in the test meal (Cn is a measure of the dilution of the remaining part of the test meal by gastric secretion and is used to calculate the volume of test meal remaining in the stomach (VR) from the 421

422

VAGNE AND ANDRE

volume of gastric contents recovered (V A): VA X CA VR=---CI The total volume passing the pylorus (VP) is obtained from the difference between the

Vol. 60, No.3

amount of phenol red in the test meal (VI X CI) and in the gastric contents after recovery (VA X CA) divided by its concentration, which is assumed to be the average of the initial and final concentration: VP

(VI X CI) - (V A X CA)

=

CI

nlUIII If 11111

+ CA

rl ..llnlng In the stomlch

2

Acid output is the sum of the amount of acid recovered and the amount of acid passing the pylorus (HCA, acid concentration in gastric contents; HCI, acid concentration in the test meal, equal to zero with a water meal):

%

300

acid output

=

(HCA X VA)

+ VP (HCA + HCI) 2

200

r

1

0.125

FIG. 1. Effect of secretin on the volume of meal remaining in the stomach 20 min after a test meal of 750 ml of water. The results are expressed as percentage of the first test performed during saline infusion. Each [lcint is the mean of two observations on each of 2 subjects. The vertical lines are the' standard errors of the means. TABLE

The volume remaining in the stomach was plotted against the logarithm of the dose of secretin. Statistical comparison between the first and the second test was performed by t-test for paired values. We also determined the regression line and correlation coefficient for volume remaining in the stomach versus acid concentration. To eliminate daily variations from the figures, the value obtained during the second test, either with saline or secretin, was expressed as a percentage of the mean of the values obtained in the first test.

Results Effect of secretin on the volume of meal remaining in the stomach. The volume of

1. Volume of meal remaining in the stomach after saline and saline plus secretin" Volume of meal remaining in the stomach

Fi rst saline

Second saline

First saline

Second secretin"

142.9 54.5 165.0 326.8

137.6 75.1 137.6 214.9

201.1 246.7 208.6 206.6

231.2 233.8 281.4 201.7

172.3 56.8

141.3 28.6

215.7 10.4

237.0 16.5

First saline

Second secretin C

First salin e

Second secretin d

302.7 204.6 144.5 158.6 214.0 204.9 27.8

278.9 190.7 150.3 159.1

309.2 430.7 344.1 495.8

194.7 29.4

394.9 42.2

ml at 20 min

Mean . . . . .. .. . SE. Mean percentage of first test .. SE percentage of first test

"Intravenous infusion . • 0.125 U per kg per hr. cO.395 U per kg per hr. d 1.250 U per kg per hr.

295.9 80.9 146.0 39.1 224.4 157.3 46.7

82.0

109.9

130.3

202.8

16.6

7.6

17.7

21.7

March 1971

meal remaining in the stomach increased with increasing doses of secretin and was related to the logarithm of the dose (t = 2,651, N = 13, P < 0,05) (fig, 1), Individual values are presented in table L Effect of secretin on gastric secretion, Acid concentration and output were lower during s'ecretin infusion than during saline

infusion (figs. 2 and 3), However, because of the large daily variations, the decrease was not statistically significant for acid output and was significant for concentration only for the largest dose of secretin (t = 3.62, N = P < 0,05), Effect of acid on gastric emptying, Under our experimental conditions duriag acid output

acid concentration

%

% 150

100

50

423

EFFECT OF SECRETIN ON GASTRIC EMPTYING

150

I

I

I 1I-

10

1r

1

r

l~r

1

,

0.'25

,

0,395

1,250

50

I

-I~)

1

secrelln u/., . ~r

0

FIG. 2. Effect of secretin on gastric acid concen· tration. The results are expressed as percentage of the first test performed during saline infusion. Each point is the mean of two observations on each of 2 subjects.

0,125

0,395

1,250

secrltln ./q.hr

FIG. 3. Effect of secretin on gastric acid output. The results are expressed as percentage of the first test performed during saline infusion . Each point is the mean of two observations on each of 2 subjects.

¥Glume af ..1.1 remaining In the stomach

Y:-9. 333X+232.8

ml at 20min r:O.782

acl~

IIIIqll 15

clllClnlratlln

2

FIG. 4. The regression of volu me of meal remaining in the stomach on acid concentration of the gastric juice obtained during saline infusion in 2 subjects,

424

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VAGNE AND ANDRE

Volume of meal remaining in the stomach at 20 min during saline and secretin infusion for the same acid concentration of the gastric contents and in the same subject

TABLE 2 .

Acid

concentration

Volum e o f meal remaining in the stomach

2.0 2.8 34 5.2 10.4

Secretin

Saline

ml at 20 min

m Eq/liter

150.3 201.1 114.8 190.7 80.9

281.4 231.2 214.0 233.8 204.9

saline infusion, we found that increasing acid concentration produced an increase in gastric emptying and the correlation was statistically significant (r = 0.782, P < 0.01) (fig. 4). For the same acid concentration and in the same subject, the volumes of meal remaining in the stomach during secretin infusion were statistically higher than during saline infusion. (t = 4.12, P < 0.02) (table 2). Discussion Chey et aI. 1 showed that secretin given as a single injection slowed gastric emptying in man. In this study, we confirmed this result by the observation of a linear relationship between the volume of meal remaining in the stomach and the logarithm of the dose of secretin. We have shown previously3 that 1.250 U per kg per hr of secretin were sub maximal dose for pancreatic secretion in man (about 80% of the maximal response). We can assume, therefore, that secretin could playa physiological role in gastric emptying by slowing it. Brooks and Grossman 4 did not observe any change in the volume of a meal collected from canine stomach after secretin infusion. This result may indicate a species difference. Secretin decreased the gastric secretion produced by distention with the test meal, as has been reported in the dog.' However, because of the variability of this secretion

from one day to another, this decrease in output of acid was not statistically significant. Hunt 2 has shown that increasing concentrations of acid decreased the rate of gastric emptying. In this study, we found that gastric emptying was linearly related to acid concentration but was increased with increasing acid concentration. We can explain this discrepancy by the fact that we measured gastric emptying for acid concentrations lower than 20 mEq per liter. At these concentrations, the slope of the curve is reversed and similar to the results Hunt obtained with sodium chloride and "almost succeeded in obtaining with 10 mN HCI." 6 Is the effect of secretin due only to changes in gastric acid secretion? We observed that, for identical acid concentrations, the gastric emptying was lower during secretin than during saline infusion . This suggests that secretin does not act only by inhibiting gastric acid secretion. It seems more likely that the decreased gastric motility induced by secretin 7 plays a role in delaying gastric emptying. REFERENCES 1. Chey WY, Hitanant S, Hendricks J, et al: Effect of intestinal hormones on human gastric function (abstr) . Gastroenterology 54:1225, 1968 2. Hunt IN : Gastric emptying and secretion in man . Physiol Rev 39:491-533, 1959 3. Vagne M, Descos L, Martin P : La secretion bicarbonate maximum du pancreas humain . CR Soc Bioi (Paris) 163:1403-1406, 1969 4. Brooks AM, Grossman MI: Effect of secretin on fasting and postprandial pH of the duodenal bulb in dogs (abstr). Gastroenterology 56:1248, 1969 5. Vagne M, Grossman MI: Gastric and pancreatic secretion in response to gastric distention . Gastroenterology 57:300-310, 1969 6. Hunt IN , Knox MJ: Regulation of gastric emptying. Handbook of Physiology, Sect 6: Alimentary Canal, vol. 4. Edited by CF Code. Washington, American Physiological Society, 1968, p 1917 7. Vagne M, Stening GF, Brooks FP, et al : Synthetic secretin: comparison with natural for potency and spectrum of physiological actions. Gastroenterology 55:260- 267, 1968