JOURNAL
OF SURGICAL
RESEARCH
18,
497-499 (1975)
The Effect of Feeding Canine
Lower
Esophageal
on the Sphincter’
J. I. HOLLENBECK, M.D., J. W. MAHER, M.D., G. WICKBOM, F. L. BUSHKIN, M.D., J. E. McGUIGAN, M.D., AND E. R. WOODWARD, M.D.
M.D.,
Departments of Surgery and Medicine, College of Medicine, University of Florida, Gainesville, Florida 32601 Submitted for publication November 8, 1974
Lower esophageal sphincter pressure (LESP) is known to increase in experimental animals and in man after the administration of exogenous gastrin or gastrin analog. This was first shown independently by two groups in 1969 [I, 31. These data led to the speculation that the lower esophageal sphincter (LES) is controlled by serum gastrin. In 1973, Grossman [4] questioned this hypothesis. He felt the response of the LES to serum gastrin concentrations might reflect the pharmacologic action of gastrin on the LES and not be a true representative of the physiologic response of the LES to the serum gastrin level. The purpose of this investigation is to determine the LESP before and after a physiologic stimulus to gastrin release.The physiologic stimulus chosen was feeding.
pressure at three points 5 cm apart through sidearm openings. Each animal had nine fasting esophageal motility tracings after which they were fed a standard 500-g horsemeat meal. Repeat tracings were obtained 50, 60, and 70 min after eating. Blood was obtained simultaneously with each motility tracing in order to determine the serum gastrin level. Serum gastrin was determined by radioimmunoassay [7].
RESULTS All dogs tolerated the cervical esophagostomies and maintained their weight. Each animal demonstrated an increase in serum gastrin concentration after feeding when compared to the fasting level (Fig. 1). The LESP did not show significant change in 11 dogs. There was a significant rise from a fasting level of 19 cm of water to a postcibal METHOD level of 48 cm of water in one dog and a Thirteen mongrel dogs weighing between significant decrease from a fasting level of 22 12 and 20 kg underwent construction of slit- cm of water to a postcibal level of 8 cm of type cervical esophagostomies. The animals water in another dog (Fig. 2). Integrated rewere allowed 2-3 wk for recovery. After sults of the group exhibited no significant inrecovery, the animals underwent standard crease in LESP after feeding. However, esophageal motility tracings using a pull- there was a significant (P < 0.01) rise in the back technique with three open-tipped cathe- postcibal serum gastrin levels (Table 1). ters, continuously perfused at a rate of DISCUSSION 0.2 cc/mm connected to external presThe effect of gastrin on the LES was sure transducers. The output from these transducers was recorded on a multichannel reported by Giles, Mason, and Humphries Honeywell recorder. The recording cathe- [3] and by Caste11 and Harris [l] independently in 1969. Giles et al. showed that ters were designed to measure intraluminal the LESP increased after the intravenous administration of gastrin and pentagastrin. ‘Supported by National Institutes of Health Grants AM13544andAM13711. They also showed an increase in the LESP 497 Copyright Q 1975 by Academic Press, Inc. All rights of reproduction in any form reserved.
498
JOURNAL OF SURGICAL
RESEARCH VOL. 18, NO. 5, MAY 1975
900 850 800 750 700 650 6m 550 E \ g
503 450 4x
FIG. 2. Basal and integrated 50-, 60-, and 70-min postcibal lower esophageal sphincter pressure for each experimental animal.
FIG. 1. Basal and integrated 50-, 60-, and 70-min postcibal serum gastrin for each experimental animal.
after the instillation of 50 ml of meat extract. They assumed that the increase after the instillation of meat extract was due to the endogenousgastrin release. Caste11and Harris demonstrated a rise in LESP after gastric alkalinization. Interpreting their data, they felt that gastric alkalinization releases gastrin and that this causes an increase in serum gastrin concentration. Therefore, the increase in LESP was the result of endogenously released gastrin. This then suggestedthat the effect of gastrin on the LES was physiologic. The physiologic role of gastrin on the LES has been questioned by Grossman. Our investigation was undertaken to determine the response of the LFS to feeding, the major physiologic stimulus to gastrin release, and to measure serum gastrin levels simultaneously with LESP measurements. TABLE 1 Mean Lower Esophageal Sphincter Pressureand Mean Serum Gastrin of the Study Animals at Time 0 (Fasting) and 50,60,70 Minutes After Feeding Time (min) Basal 50 60 70
Mean LES pressure (cm Hz0 f SEM) 22.5 f 17.4 f 21.2 t 20.9 f
2.1 1.5 2.3 2.1
Mean serum gastrin (pg/d * SEMI 78* 18 257 * 63 252 + 72 283 f 82
Although serum gastrin increased after feeding, there was no significant change in the LESP. These data suggest that gastrin is not the sole determinant of the LESP. Higgs, Smyth, and Caste11 (5) recently showed that as previously described gastric alkalinization is associated with an increase in LESP. They were unable to show an increase in circulating gastrin. Farrell, Castell, and McGuigan (2) showed that after a meat meal the human LESP is increased significantly over fasting levels and that the serum gastrin concentration was also increased significantly. Lipshutz and Cohen have shown that secretin reduces the reponse of the LFS muscle to gastrin. Circulating secretin, as well as gastrin, is increased after feeding [8]. The data presented in this paper are not presented to establish or reject the role of gastrin in control of the lower esophageal sphincter pressure. We only suggest, however, that our data cast doubt on the hypothesis that gastrin is the only hormonal regulator of the LESP. We think that the physiologic response of the LESP must be studied further in an attempt to determine what other neurologic and hormonal actions contribute in this complex sphincter control. CONCLUSION Thirteen mongrel dogs were studied to determine the effect of feeding on the LISP and on serum gastrin concentration measured simultaneously with the LESP.
HOLLENBECK
ET AL.: FEEDING AND ESOPHAGEAL SPHINCTER
We found a significant (P < 0.01) rise in serum gastrin after feeding, but no significant change in the lower esophageal sphincter pressure. We feel that there may be a number of undefined stimuli contributing to the physiologic actions of the lower esophageal sphincter. REFERENCES I. Castell, D. O., and Harris, L. D. Hormonal control of gastroesophageal sphincter strength. N. Engl. J. Med. 2@:886, 1970. 2. Farrell, R. L., Castell, D. O., and McGuigan, J. E. Measurements and comparisons of lower esophageal sphincter pressures and serum gastrin levels in patients with gastroesophageal reflux. Gasrroenterology67:415, 1974. 3. Giles, G. R., Mason, M. C., Humphries, C., and
499
Clark, C. G. Action of gastrin on the lower esophageal sphincter in man. Gut 10:730, 1969. 4. Grossman, M. I. What is physiological? Gastroenterology
65994, 1974.
5. Higgs, R. H., Smyth, R. D., and Castell, D. 0. Gastric alkalinization: Effect on lower esophageal sphincter and gastrin. N. Engl. J. Med 291:486, 1974. 6. Lipshutz, W. H., and Cohen, S. Interaction of gastrin I and secretin on gastrointestinal circular muscle. Am. J. Physiol. 222~775, 1972. 7. McGuigan, J. E., and Trudeau, W. L. Studies with antibodies to gastrin: Radioimmunoassay in human serum and physiological studies. Gusrroenterology 58:139,1970. 8. Meyer, J. H. Release of secretin and cholecystokinin. In W. Y. Chey and F. P. Brooks (Eds.), Endocrinology of the Gut, pp. 241-252. Slack, Thorofare, N.J., 1974.
OF SURGICAL
RESEARCH
18,
497-499 (1975)
The Effect of Feeding Canine
Lower
Esophageal
on the Sphincter’
J. I. HOLLENBECK, M.D., J. W. MAHER, M.D., G. WICKBOM, F. L. BUSHKIN, M.D., J. E. McGUIGAN, M.D., AND E. R. WOODWARD, M.D.
M.D.,
Departments of Surgery and Medicine, College of Medicine, University of Florida, Gainesville, Florida 32601 Submitted for publication November 8, 1974
Lower esophageal sphincter pressure (LESP) is known to increase in experimental animals and in man after the administration of exogenous gastrin or gastrin analog. This was first shown independently by two groups in 1969 [I, 31. These data led to the speculation that the lower esophageal sphincter (LES) is controlled by serum gastrin. In 1973, Grossman [4] questioned this hypothesis. He felt the response of the LES to serum gastrin concentrations might reflect the pharmacologic action of gastrin on the LES and not be a true representative of the physiologic response of the LES to the serum gastrin level. The purpose of this investigation is to determine the LESP before and after a physiologic stimulus to gastrin release.The physiologic stimulus chosen was feeding.
pressure at three points 5 cm apart through sidearm openings. Each animal had nine fasting esophageal motility tracings after which they were fed a standard 500-g horsemeat meal. Repeat tracings were obtained 50, 60, and 70 min after eating. Blood was obtained simultaneously with each motility tracing in order to determine the serum gastrin level. Serum gastrin was determined by radioimmunoassay [7].
RESULTS All dogs tolerated the cervical esophagostomies and maintained their weight. Each animal demonstrated an increase in serum gastrin concentration after feeding when compared to the fasting level (Fig. 1). The LESP did not show significant change in 11 dogs. There was a significant rise from a fasting level of 19 cm of water to a postcibal METHOD level of 48 cm of water in one dog and a Thirteen mongrel dogs weighing between significant decrease from a fasting level of 22 12 and 20 kg underwent construction of slit- cm of water to a postcibal level of 8 cm of type cervical esophagostomies. The animals water in another dog (Fig. 2). Integrated rewere allowed 2-3 wk for recovery. After sults of the group exhibited no significant inrecovery, the animals underwent standard crease in LESP after feeding. However, esophageal motility tracings using a pull- there was a significant (P < 0.01) rise in the back technique with three open-tipped cathe- postcibal serum gastrin levels (Table 1). ters, continuously perfused at a rate of DISCUSSION 0.2 cc/mm connected to external presThe effect of gastrin on the LES was sure transducers. The output from these transducers was recorded on a multichannel reported by Giles, Mason, and Humphries Honeywell recorder. The recording cathe- [3] and by Caste11 and Harris [l] independently in 1969. Giles et al. showed that ters were designed to measure intraluminal the LESP increased after the intravenous administration of gastrin and pentagastrin. ‘Supported by National Institutes of Health Grants AM13544andAM13711. They also showed an increase in the LESP 497 Copyright Q 1975 by Academic Press, Inc. All rights of reproduction in any form reserved.
498
JOURNAL OF SURGICAL
RESEARCH VOL. 18, NO. 5, MAY 1975
900 850 800 750 700 650 6m 550 E \ g
503 450 4x
FIG. 2. Basal and integrated 50-, 60-, and 70-min postcibal lower esophageal sphincter pressure for each experimental animal.
FIG. 1. Basal and integrated 50-, 60-, and 70-min postcibal serum gastrin for each experimental animal.
after the instillation of 50 ml of meat extract. They assumed that the increase after the instillation of meat extract was due to the endogenousgastrin release. Caste11and Harris demonstrated a rise in LESP after gastric alkalinization. Interpreting their data, they felt that gastric alkalinization releases gastrin and that this causes an increase in serum gastrin concentration. Therefore, the increase in LESP was the result of endogenously released gastrin. This then suggestedthat the effect of gastrin on the LES was physiologic. The physiologic role of gastrin on the LES has been questioned by Grossman. Our investigation was undertaken to determine the response of the LFS to feeding, the major physiologic stimulus to gastrin release, and to measure serum gastrin levels simultaneously with LESP measurements. TABLE 1 Mean Lower Esophageal Sphincter Pressureand Mean Serum Gastrin of the Study Animals at Time 0 (Fasting) and 50,60,70 Minutes After Feeding Time (min) Basal 50 60 70
Mean LES pressure (cm Hz0 f SEM) 22.5 f 17.4 f 21.2 t 20.9 f
2.1 1.5 2.3 2.1
Mean serum gastrin (pg/d * SEMI 78* 18 257 * 63 252 + 72 283 f 82
Although serum gastrin increased after feeding, there was no significant change in the LESP. These data suggest that gastrin is not the sole determinant of the LESP. Higgs, Smyth, and Caste11 (5) recently showed that as previously described gastric alkalinization is associated with an increase in LESP. They were unable to show an increase in circulating gastrin. Farrell, Castell, and McGuigan (2) showed that after a meat meal the human LESP is increased significantly over fasting levels and that the serum gastrin concentration was also increased significantly. Lipshutz and Cohen have shown that secretin reduces the reponse of the LFS muscle to gastrin. Circulating secretin, as well as gastrin, is increased after feeding [8]. The data presented in this paper are not presented to establish or reject the role of gastrin in control of the lower esophageal sphincter pressure. We only suggest, however, that our data cast doubt on the hypothesis that gastrin is the only hormonal regulator of the LESP. We think that the physiologic response of the LESP must be studied further in an attempt to determine what other neurologic and hormonal actions contribute in this complex sphincter control. CONCLUSION Thirteen mongrel dogs were studied to determine the effect of feeding on the LISP and on serum gastrin concentration measured simultaneously with the LESP.
HOLLENBECK
ET AL.: FEEDING AND ESOPHAGEAL SPHINCTER
We found a significant (P < 0.01) rise in serum gastrin after feeding, but no significant change in the lower esophageal sphincter pressure. We feel that there may be a number of undefined stimuli contributing to the physiologic actions of the lower esophageal sphincter. REFERENCES I. Castell, D. O., and Harris, L. D. Hormonal control of gastroesophageal sphincter strength. N. Engl. J. Med. 2@:886, 1970. 2. Farrell, R. L., Castell, D. O., and McGuigan, J. E. Measurements and comparisons of lower esophageal sphincter pressures and serum gastrin levels in patients with gastroesophageal reflux. Gasrroenterology67:415, 1974. 3. Giles, G. R., Mason, M. C., Humphries, C., and
499
Clark, C. G. Action of gastrin on the lower esophageal sphincter in man. Gut 10:730, 1969. 4. Grossman, M. I. What is physiological? Gastroenterology
65994, 1974.
5. Higgs, R. H., Smyth, R. D., and Castell, D. 0. Gastric alkalinization: Effect on lower esophageal sphincter and gastrin. N. Engl. J. Med 291:486, 1974. 6. Lipshutz, W. H., and Cohen, S. Interaction of gastrin I and secretin on gastrointestinal circular muscle. Am. J. Physiol. 222~775, 1972. 7. McGuigan, J. E., and Trudeau, W. L. Studies with antibodies to gastrin: Radioimmunoassay in human serum and physiological studies. Gusrroenterology 58:139,1970. 8. Meyer, J. H. Release of secretin and cholecystokinin. In W. Y. Chey and F. P. Brooks (Eds.), Endocrinology of the Gut, pp. 241-252. Slack, Thorofare, N.J., 1974.
