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Gastrointestinal Defence Mechanisms. Satellite Symposium of the 28th International Congress of Physiological Sciences, Pécs, Hungary, 1980 PDF

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ADVANCES IN PHYSIOLOGICAL SCIENCES Proceedings of the 28th International Congress of Physiological Sciences, Budapest 1980 Volumes 1 — Regulatory Functions of the CNS. Principles of Motion and Organization 2 — Regulatory Functions of the CNS. Subsystems 3 — Physiology of Non-excitable Cells 4 — Physiology of Excitable Membranes 5 — Molecular and Cellular Aspects of Muscle Function 6 — Genetics, Structure and Function of Blood Cells 7 — Cardiovascular Physiology. Microcirculation and Capillary Exchange 8 — Cardiovascular Physiology. Heart, Peripheral Circulation and Methodology 9 — Cardiovascular Physiology. Neural Control Mechanisms 10 — Respiration 11 — Kidney and Body Fluids 12 — Nutrition, Digestion, Metabolism 13 — Endocrinology, Neuroendocrinology, Neuropeptides — I 14 — Endocrinology, Neuroendocrinology, Neuropeptides — II 15 — Reproduction and Development 16 — Sensory Functions 17 — Brain and Behaviour 18 — Environmental Physiology 19 — Gravitational Physiology 20 — Advances in Animal and Comparative Physiology 21 — History of Physiology Satellite symposia of the 28th International Congress of Physiological Sciences 22 — Neurotransmitters in Invertebrates 23 — Neurobiology of Invertebrates 24 — Mechanism of Muscle Adaptation to Functional Requirements 25 — Oxygen Transport to Tissue 26 — Homeostasis in Injury and Shock 27 — Factors Influencing Adrenergic Mechanisms in the Heart 28 — Saliva and Salivation 29 — Gastrointestinal Defence Mechanisms 30 — Neural Communications and Control 31 — Sensory Physiology of Aquatic Lower Vertebrates 32 — Contributions to Thermal Physiology 33 — Recent Advances of Avian Endocrinology 34 — Mathematical and Computational Methods in Physiology 35 — Hormones, Lipoproteins and Atherosclerosis 36 — Cellular Analogues of Conditioning and Neural Plasticity (Each volume is available separately.) ADVANCES IN PHYSIOLOGICAL SCIENCES Satellite Symposium of the 28th International Congress of Physiological Sciences Pecs, Hungary 1980 Volume 29 Gastrointestinal Defence Mechanisms Editors Gy. Mozsik Pecs, Hungary O. Hanninen Kuopio, Finland T. Javor Pecs, Hungary PH PERGAMON PRESS AKADEMIAI KIADO Pergamon Press is the sole distributor for all countries, with the exception of the socialis t countries. HUNGARY Akademiai Kiado, Budapest, Alkotmany u. 21. 1054 Hungary U.K. Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, England U.S.A. Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, New York 10523, U.S.A. CANADA Pergamon of Canada, Suite 104, 150 Consumers Road, Willowdale, Ontario M2J IP9, Canada AUSTRALIA Pergamon Press (Aust.) Pty. Ltd., P.O. Box 544, Potts Point, N.S.W. 2011, Australia FRANCE Pergamon Press SARL, 24 rue des Ecoles, 75240 Paris, Cedex 05, France FEDERAL REPUBLIC Pergamon Press GmbH, 6242 Kronberg-Taunus , OF GERMANY Hammerweg 6, Federal Republic of Germany Copyright © Akademiai Kiado, Budapest 1981 AH rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic tape, mechanical,photo- copying, recording or otherwise, without permission in writing from the publishers. British Library Cataloguing in Publication Data International Congress of Physiological Sciences, Satellite Symposium (28th : 1980 : Pecs Advances in physiological sciences. Vol. 29 : Gastrointestinal defence mechanisms 1. Physiology — Congresses I. Title II. Mozsik, Gy III. Hanninen, Ο IV. Javor, Τ V. Gastrointestinal defence mechanisms 591.1 QPI 80-41883 Pergamon Press ISBN 0 08 026407 7 (Series) ISBN 0 08 027350 5 (Volume) Akademiai Kiado ISBN 963 05 2691 3 (Series) ISBN 963 05 2713 8 (Volume) In order to make this volume available as economically and as rapidly as possible the authors^ typescripts have been reproduced in their original forms. This method unfortunately has its typographi- cal limitations but it is hoped that they in no way distract the reader. Printed in Hungary 1. Clara Sajgo (Budapest, Hungary) 2. E. Ezer (Budapest, Hungary) 3. Elisabeth Fay (Budapest , Hungary) 4. M. Kondo (Kyoto, Japan) 5. L. Csalay (Budapest, Hungary) 6. O. Hanninen (Kuopio, Finland) 7. H. Autrup (Bethesda, USA) 8. M. Ahotupa (Turku, Finland) 9. M. Sajgo (Budapest, Hungary) 10. Judith Matuz (Budapest, Hungary) 11. E. Hietanen (Turku, Finland) 12. J. Szolcsanyi (Pecs, Hungary) 13. G. Csakvari (Budapest, Hungary) 14. A.-M. Saamanen (Kuopio, Finland) 15. M. Outi (Kuopio, Finland) 16. Noemi Prajda (Budapest, Hungary) 17. Judith Kralovanszky (Budapest, Hungary) 18. Gy. Mozsik (Pecs, Hungary) 19. Gy. Szabo (Budapest , Hungary) 20. A. Gad (Falun, Sweden) 21. D. van der Waaij (Groningen, The Netherlands) 22. P. B. Morat (London, England) 23. B. Simon (Heidelberg, FRG) 24. L. Nagy (Pecs, Hungary) 25. E. Heimsch (Ulm, FRG) 26. T. Javor (Pecs, Hungary) 27. F. Varga (Pecs, Hungary) 28. S. M. Morrissay (London, England) 29. T. Bero (Pecs, Hun- gary) 30. C. D. Klaassen (Kansas City, USA) 31. Kornelia Javor (Pecs, Hungary) 32. F. Tarnok (Pecs, Hungary) 33. G. Tatar (Budapest, Hungary) 34. J. Szantay (Cluj-Napoca, Romania) ν PREFACE The gastrointestinal tract has an important service function in the body. It stores ingested food and beverages for digestion, prepares the various components for absorption, transfers actively physiologically necessary com- pounds into the blood stream and lympharoutes. On the other hand, the gastrointestinal tract performs also excretory functions. Faeces form togeth- er with the urine the two major means by which the body can get rid of the solid and liquid vastes. Thus the gastrointestinal tract contributes in many ways to the homeostasis in body. All these functions have gained a lot of interest among scientists throughout the world, and many of these functions have been clarified in details. In addition to the various functions mentioned above the gastrointes- tinal tract carries out also functions related to the defence of the body against biological, chemical and physical agents. The gastrointestinal defence mechanisms have not been for many years—in fact for decades—under a separated detailed review. Therefore the Finnish Physiological Society suggested to the Organizing Committee of the 28th International Congress of Physiological Sciences to hold the Gastrointestinal Defence Mechanisms as a topic of a satellite symposium after the main congress. The suggestion was accepted and the colleagues at the P6cs University Medical School were ready to take the local responsibility for organizing the meeting. The First International Symposium on the Gastrointestinal Defence Mechanisms was held on July 20-22, 1980 in the University Medical School of Pics, Hungary. Dr. Kaarlo Hartiala acted as the chairman of the Organiz- ing Committee and Drs. Eino Hietanen, Osmo Hanninen, Tib or Jdvor and Gyula Mozsik as members. The aim of the symposium was to call together research workers study- ing both the theoretical and practical aspects of the various gastrointestinal defence mechanisms. This aim was reached as evidenced by the almost 40 pa- pers presented during the symposium and found in the volume. Eleven of them are more or less review type and others primary research reports. Thus, although rather short period of time was available for the distribution of message about the meeting, nearly all the topics could be included. To help the readers, the papers of the volume have been divided into eight sections carrying the subheadings: Circulation and Mucosal Defence, xi Defence and Secretory Functions, Resistance and Toxicity, Pefence by Biotransformation and Nutrition, Immunomechanisms on Defence at Mucosa and Second Line Defence at Liver and Enterohepatic Circulation. All the sections contain few papers each. The meeting showed that the research of the gastrointestinal defence mechanisms requires an application of several methodologies and interdisci- plinary approach. The conference brought together scientists with different background, and we do hope that this book gets into the hands also of those working in other fields and turns their interests to the gastrointestinal de- fence mechanisms. The following years will show, if the exposure has been fruitful and a Second International Symposium on the Gastrointestinal De- fence Mechanisms convenes. Pecs July 24th, 1980 Gyula MOZSIK, Osmo HANNINEN and Tibor JAVOR xii WELCOMING ADDRESS On the contrary to my long-term plans I have to make a last minute cancellation due to health problems to attend the International Sympo- sium on Gastrointestinal Defence Mechanisms. I personally expected much of it as a stimulus of further work in this field which I myself had an opportunity to enter about thirty years ago in the guidance of Dr. A. C. Ivy. Dr. Ivy was an ideal rich and hard working scientist who contributed much to various discoveries in the physiology and pathophysiology of the gastro- intestinal tract. Dr. Ivy got me as well as many others infected by his enthusiasm. His pupils in various parts of the world have provided much of the knowledge we now have on the functions of the normal and disturbed gastrointestinal tract. Although the society has changed with it certain health problems even related to the gastrointestinal tract, there is a lot to be done to solve the basic mechanisms of the gastrointestinal defence in the gastrointestinal tract. I myself have been interested in the biotransformation reactions and gly- coproteins and can see so many questions still waiting for an answer. The increasing use of various purposes means a big challenge for our gastrointes- tinal tract and at the same time also a challenge to research workers trying to clarify the defence mechanisms at this portal of entry. The program of the First International Symposium on the Gastrointes- tinal Defence Mechanisms has good coverage of the research work done in many countries. Therefore I feel pity for being unable to participate. With these lines I should like to thank with all my heart to the Hungarian colleagues for seeing all the troubles of organizing the meeting and also the Hungarian Academy of Sciences and its Publishing House (Akademiai Ki- ado), Budapest—together with Pergamon Press, Oxford—for taking care of the symposium proceedings. Wishing all success to the meeting in Turku on 9th July 1980 Kaarlo HARTIALA xiii Adv. Physiol Set. Vol. 29. Gastrointestinal Defence Mechanisms Gy. Mozsik, 0. Hanninen, T. Javor (eds) CIRCULATORY RESPONSES TO CHANGES OF INTESTINAL CONTENTS G. Szabo and I. Benyo Traumatological Research Unit and Third Department of Surgery, Semmelweis University Medical School, Budapest, Hungary Metabolic and circulatory changes during digestion and ab- sorption of food were analysed already by Brodie et al. in 1910. Many studies have since confirmed that blood flow in the supe- rior mesenteric vascular bed increases following a meal. This postprandial mesenteric hyperaemia has been observed in man /Brandt et al., 1955; Degenais et al. 1966/, conscious primate /Vatner et al. 1974/, anaesthetized and conscious dogs /Burns and Schenk, 1969; Fronek and Stahlgren, 1968; Varro et al., 1967; Vatner et al. 1970/ and rats /Reininger and Sapirstein, 1957/. The blood flow through the superior mesenteric artery in dogs starts to increase within 5 to 15 min following food in- take, reaches a maximum in 30-90 and lasts for 3-7 h /Burns and Schenk, 1969; Fronek and Stahlgren, 1968; Vatner et al. 1970/. If food constituents are introduced directly into the duodenum the circulatory reaction begins in less than 10 min /Chou et al 1976/. The maximal increase in mesenteric blood flow is 150-200 % but usually the augmentation is well below 100 %. This seems to be a rather moderate increase because propranolol e.g. may produce a much greater augmentation of flow /Lundgren 1967/. There might be several reasons for the moderateness of this prostprandial vasodilatation. In the above studies the blood flow was measured to the gastrointestinal tract as a whole. It seems unlikely, however, that maximal vasodilatation occurs si- multaneously in ever part of it. The vasodilatation might be localized to the mucosa with no or only moderate changes in the perfusion of the muscular layer. It seems that intestinal moti- lity as such does not increase significantly total intestinal blood flow /Lundgren 1967/ and that the absorption of certain foods may not induce any conspicious flow changes /Brand et al. 1955/. The composition of the ingested food and its degree of digestion might be an important factor in the production of the gastrointestinal flow response. Moreover, certain food consti- tuents may increase the blood flow in some part of the gastro- intestinal tract, but be without effect on the circulation of other parts. Let us see a few examples for the above proposi- tions . 3 While undigested food introduced into the duodenal or jeju- nal lumen failed to increase venous outflow from the exteriori- zed intestinal loop, digested food or its supernatant increased it significantly by 13 % and 11 %, respectively /Chou et al. 1976, 1978/. In the jejunum bile alone had no effect, but intro- duced in the ileal lumen it increased local blood flow and it also markedly enhanced the hyperaemic effect of digested food in the jejunum. Glucose solution increased the circulation of the isolated jejunal loop in the dog /Varro et al. 1967/. The intestinal hyperaemia is limited, however, only to the perfused teritory /Van Heerder et al. 196 8/ and the increase of flow occurs mainly in the mucosal layer /Yu and al. 1975/. Intraduo- denal fat augmented flow in the cat superior mesenteric artery by 50-100 % /Fara and al. 1969/. At physiological postprandial concentrations in the jejunum micellar solutions of oleic acid and monoolein increased flow, but 16 common dietary amino acids did not. The hyperaemic effect of lipids required the presence of taurocholate /Chou and al. 1978/. The concentration of nutritients in the jejunal lumen must exceed a certain value to produce local hyperaemia and, gener- ally speaking, the greater the concentration of nutritients in the chyme the greater the resultant hyperaemia. The differences in circulatory effects are, however, not due to differences in the osmolarity of the solutions since an unabsorbeable substan- ce with the same osmotic concentration does not increase intes- tinal blood flow /Kvietys and al. 1976/. It seems, however, that the composition of the ingested food is not the only factor leading to haemodynamic changes. It was only recently realized that the cardiovascular system responds to feeding in two distinctly different phases. During presentation and ingestion of food cardiac output, heart rate arterial pressure and vascular resistance in various vascular beds are altered in a pattern similar to that observed at the increase in sympathetic neural activity. Within 5-30 min, how- ever cardiac output, heart rate, arterial pressure, the perfu- sion of the kidney and of the myocardium return to control levels, while mesenteric blood flow starts to rise. In humans anticipated feeding increases also vagally mediated gastric acid secretion /Moor and Motoki, 1979/. Pure psychic stimula- tion may be as effective stimulant as feeding. The observations suggest that in the first phase the anticipation and/or inges- tion of food elicit a secretory and generalized cardiovascular reaction, in the second phase i.e. during the digestion when the ingested food reaches the intestines there is a circulatory response confined to the digestive organs /Burns and Schenk, 1969; Fronek and Fronek, 1970; Vatner et al., 1970, 1974/. On the other hand some textbooks state that there are nervous re- ceptors in the walls of the duodenum stimulated by high concen- tration of hydrogen ions and that the acidification of the duo- denal contents leads even in absence of any food to marked changes in gastrointestinal macro- and micromotility and secre- tory activity. The automatic movements of the intestinal villi are stimulated and their capillaries are dilated /Ludany et al. 1959/. The hepatic blood flow, measured with coupled thermo- elements, hydrogen wash-out technique or BSP-clearance is sig- nificantly increased /Benyo et al., 1965, 1966, 1974/. 4 In the studies about the effect of various nutritients on gastrointestinal circulation usually only the superior mesente- ric artery flow /SMAF/ has been measured. There are only a few informations available concerning the effect of a meal on coe- liac artery flow, which supplies the liver, stomach, duodenum and pancreas. In order to gain information about the flow chan- ges in the whole splanchnic vascular bed in the first series of our experiments we have studied in dogs with non-cannulating electromagnetic flow probes the effect of acidifying the duode- nal contents on the blood flow in the hepatic artery and in the portal vein. In 13 mongrel dogs the ba- sal blood flow in the hepatic artery /HAF/ was 13.6 (SEM + 1.3) ml / min/100 g tissue weight ml min1 100q in the portal vein /PVF/ 20Ch 46.6 + 7.0 and total hepatic blood flow /HBF/ was 53.5 + teu 6.3 ml/min/kg. After the AHFVPFHBF introduction of 3 ml/kg body weight 0.1 Μ hydrochloric acid into the duodenal lumen HAF increased by 24.7 %, PVF by 31.3 % and HBF by 29.2 %. Maximum HAF change was attain- ed in 2 to 7 min and the reac- tion lasted 8 to 30 min. The arterial and venous reaction:- were usually not entirely AHF VPFHBF synchronous. In the first mi- nute after acid introduction there was usually a drop in arterial blood pressure, af- ter which it returned to near- ly control level. At the same time there was a small increa- se in portal venous pressure. Hepatic artery inflow resis- tance decreased by 11 %. The most prominent change was the 32.5 % drop in mesenteric arteriolar resistance. /Fig.1,2/ These experiments have Fig. Effect of duodenal ins- shown that the introduction tTlIation of 0.1 and 0.5 Μ hyd- of acid into the duodenum rochloric acid on hepatic arte- leads to a transitory increase ry IAHFI, portal vein /VPF/ and in mesenteric blood flow last- total hepatic blood flow /HBF/ ing about 30 min. If it is in anaesthetized dogs. supposed that the flow reac- F: blood flow, ml/min/100 g or- tion is due to chemoreceptor gan weight. White columns: be- stimulation, it can be assumed fore acid introduction; Shaded that a stronger stimulus would columns: after acid. elicit a greater response and that a prolonged stimulation leads to a sustained flow reaction. Actually in 5 dogs 5

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