little or no regard has been paid to the analysis of the movements of (maximal relaxation) manifests itself during the height of antral

Transcription

1 6I THE REGULATION OF THE PYLORIC SPHINCTER. BY B. A. McSWINEY AND L. N. PYRAH. (From the Department of Physiology, The University of Leeds.) CONSIDERABLE discussion has taken place as to the mechanism regulating the opening and closing of the pyloric sphincter since Cannon in 1907 enunciated his theory of the acid and alkali control. Unfortunately, as Alvarez [1928 a] points out, commentators have not infrequently quoted incorrectly and, further, have failed to note that Cannon had seen defects in his theory, as in certain conditions it did not explain all the facts. An excellent summary of the literature on the control of the pylorus is given by Alvarez. In most of the investigations described, attention has been directed to the consistency or reaction of the foodstuff, and little or no regard has been paid to the analysis of the movements of the pyloric antrum and sphincter. Wheelon and Thomas [1920, 1922], however, have studied the relation between the sphincter and antral contractions in dogs by means of an enterograph introduced into the antrum. These observers show that the pyloric sphincter has cycles of rhythmic motility and that these cycles are coincident and of the same duration and rhythm as those of the antrum proper. "A phase of inhibition (maximal relaxation) manifests itself during the height of antral contraction. Following this, and while the antrum is finishing its contraction, the sphincter begins its positive phase and reaches the height of its contraction when the antrum is rapidly relaxing or has relaxed. Following this, the sphincter relaxes." They further suggest that the sphincter may act not only in relation to the antrum to aid in the propulsion of material from the stomach, but also as a barrier to the regression of chyme during the presence of a positive phase of the duodenum. The co-ordination which exists between the movements of the antrum and the pyloric sphincter and the part played by the sphincter in regulating the passage of fluid may be studied by using the preparation described by McCrea and McSwiney [1926]. It has been possible to

2 128 B. A. McSWINEY AND L. N. PYRAH. separate the antrum from the body of the stomach without interference with the nerve or blood supply and to record simultaneously the contractions of the antrum and the amount of fluid flowing through the sphincter. The method has distinct advantages, as there is no disturbance of the pyloric sphincter. METHOD. Dogs have been used in these experiments. The animal was first ansesthetized with ether, sustained aneesthesia being obtained by intravenous chloralose (0.07 g. per kg.). A second injection was occasionally necessary some 2-4 hours later. The abdomen was opened through a mid-line incision, and the body of the stomach separated from the pyloric antrum. The distal end of the body was then closed by a running Czerny-Lembert suture. A wide-bore cannula was inserted and tied into the antrum. Alternatively, a ligature may be passed through the greater and lesser omentum close to the curvatures of the stomach at the incisura, and tied tightly round the junction of the antrum and the body; a small opening is made into the antrum near to the point of ligature, and a cannula inserted and securely tied. A method suggested by Babkin [1931] was used in several of the earlier experiments. In the region of the incisura a longitudinal incision 1 in. long was made through the seromuscular coat to the mucosa midway between the greater and lesser curvatures, and a tube of mucous membrane was separated from the seromuscular coat. A cannula was inserted into the tube which was then tied off. The duodenum was divided transversely 1 in. from the pylorus. A wide cannula was tied into the proximal end, 1 in. distal to the pylorus. Rubber tubing connected the cannula with a U-tube manometer. The fluid, escaping from the antrum, flowed into one limb of the manometer, and was recorded on the kymograph by the movement of the waterfloat; the level of the fluid in the manometer may be lowered after a series of contractions to its resting level. An interval of approximately min. was allowed to elapse after the operation; the cannula in the antrum was then attached to the tube leading from a reservoir supported 2 ft. above the level of the antrum. A valve was placed at the lower end of the tube, and this allowed fluid to flow into the antrum only during the relaxation phase. A tube, attached to a tambour for recording antral contractions, was connected to the inflow tube below the valve. The tap of the reservoir was opened, and the rate of inflow was varied

3 REGULATION OF THE PYLORIC SPHINCTER. by inserting capillary tubes of different calibres into the rubber cork of the reservoir. The reservoir is placed at a height above the animal to ensure "diastolic" filling. The pressure was never sufficient to open the sphincter, which is able to resist comparatively high pressures. The pressure of the fluid does not therefore determine the rate of escape of fluid from the antrum, but merely ensures adequate filling. EXPERIMENTAL RESULTS. Simultaneous records of the contraction of the antrum and the amount of fluid flowing through the sphincter were first obtained using 0 9 p.c. sodium chloride solution as the inflow fluid. Slight movements are observed even before fluid fills the antrum, but well-marked contractions do not occur until the antrum is distended [Ducchesi, 1913]. The amplitude of contractions varied in different animals, but the height of the contraction wave was remarkably constant in the same animal for any given rate of inflow. The height of contraction was found to vary with the inflow, and, if the rate of inflow was increased, the amplitude of contraction increased. The form of the antral contraction was observed to be constant, and consisted of an even ascent and descent of the curve, except for a concavity on the rising limb which marks the opening of the pyloric sphincter. Small superimposed respiratory waves are usually present. A large contraction occurring in a series of regular waves was generally preceded by a longer period of diastole. The frequency of contraction remained remarkably constant throughout the experiment, and little or no change was observed on altering the inflow. The saline solution was expelled from the antrum through the sphincter in spurts or jets which synchronized with the antral contractions. The outflow of fluid from the antrum was recorded, and, as fluid only escaped during the antral systole, a step-like tracing was obtained. If fluid enters the antrum too rapidly, or if, owing to the bad condition of the animal, the sphincter is not able to hold back the fluid, the tracing illustrating the outflow becomes a continuous rising line. The state of the pyloric sphincter is therefore indicated by the type of outflow curve. It has previously been observed that the height of the antral contraction varies with diastolic filling. In the same way, the amount of saline solution expelled with each contraction varies with the inflow. With a constant rate of inflow, the amounts expelled at each contraction vary slightly from one another, but increase in inflow causes a greater antral contraction with a corresponding increase of outflow. PH. LXXVI

4 130 B. A. McSWINEY AND L. N. PYRAH. Inflow Small Medium Large TABLE I. Height of contractions (antrum) cm. 2* Frequency of contractions (antrum) per 3 min Average outflow per contraction c.c Fig. 1. Tracing to show relation between (P) contraction of pyloric antrum and (0) outflow of saline through the pyloric sphincter. Time interval 1 sec. The size of antral contraction is not, however, the only factor regulating the outflow, as not infrequently a larger amount of fluid is expelled with a small contraction than with a large contraction. It would appear, therefore, that the amount of outflow with a constant inflow depends on (a) the contraction of the pyloric antrum, and (b) the relaxation of the pyloric sphincter. It is clear that the extent and duration of the relaxation period of the sphincter must be the principal factor determining the outflow. Tracings illustrating the relation between the movements of the antrum and the pyloric sphincter (Fig. 1) have been obtained. The time

5 REGULATION, OF THE PYLORIC SPHINCTER. 131 intervals will, of course, vary in each experiment according to the frequency of contraction and other factors. In Table II a series of measurements obtained with saline is recorded. It will be observed that the outflow commenced some 2-4 sec. after the TABLE II. Saline, constant inflow. Interval Contraction between Height of Amount Time (antrum) contraction contraction of of,- - and (antrum) outflow outflow Ascending Descending outflow cm. c.c. sec. sec. sec. sec. Dog * Dog Dog *2 6 4 Dog ' * onset of the contraction of the pyloric antrum. The outflow usually lasted for some 4-6 sec. and ceased before the antrum relaxed. It may, therefore, be stated that the pyloric sphincter relaxes for a period of approximately 4-6 sec. during the period of antral contraction. It must be emphasized that in all our experiments the sphincter remained contracted except for short periods of the antral cycle. The measurements given in Table II are not strictly accurate, as a lag occurs between the contraction of the antrum and the reception of fluid in the manometer. A series of experiments has been made on the effects of various fluids upon the activity of the sphincter pylori. It is usually stated that fats leave the stomach at a slower rate than proteins, and again that solid and semi-solid foods empty less quickly than liquid. Considerable variation in the rate of outflow of liquids from the stomach is further described. Acid fluids empty at a slower rate than neutral solutions, and alkaline solutions empty at a rate which is between that of acids and neutral solutions [Alvarez, 1928 b]. To determine whether acid, alkali, salt, organic acid or viscous solutions influence the state of the pyloric sphincter, the passage of the following fluids through the pyloric antrum was investigated. I. Sodium chloride, 09 p.c.; sodium chloride, 2 p.c.; distilled water; glucose, 2 p.c.; hydrochloric acid, 018 p.c. in normal saline; sodium bicarbonate, 0-2 p.c. in normal saline. 9-2

6 132 B. A. McSWINEY AND L. N. PYRAH. II. Olive oil; gum acacia, 10 p.c. and 2 p.c. in normal saline. III. Organic acids, 2 p.c. solutions; lactic, malic, succinic, tartaric and caproic acids. Fig. 2. Tracing to show relation between (P) contraction of pyloric antrum and (0) outflow of fluid through the pyloric sphincter. A, saline; B, alkali; C, acid. Time interval 30 sec. The contractions of the pyloric antrum and the outflow of fluid through the sphincter were first recorded, using 0*9 p.c. sodium chloride solution. At the end of this initial experiment the inflow fluid was

7 REGULATION OF THE PYLORIC SPHINCTER. 133 changed over, and comparable tracings were taken with one of the test solutions. Each preparation was used to test three or four solutions. TABLE III. Contraction Interval between Height of Amount Time (antrum) contraction contraction of of A and (antrum) outflow outflow Ascending Descending outflow Fluid cm. c.c. sec. sec. sec. sec. Saline Saline 6*3 6* Alkali Alkali Acid Acid 4*1 6* Two readings are given for each fluid, the first set of readings being taken shortly after the start, and the second towards the end of the experiment. The inflow was constant throughout. The results obtained with the fluids of Groups I, II, III were in no way different from those obtained with saline. Records and measurements made using saline, alkali and acid are given in Fig. 2 and Tables III and IV. The base line of the antral contractions remained remarkably constant, demonstrating that there was no appreciable change of tonus. When the inflow fluid is first changed over, the antral contractions and the outflow curve occasionally become irregular for a short interval. The preparation, however, soon settles down, and regular records are obtained. TABLE IV. Average height Frequency of of contraction contraction Average (antrum) (antrum) outflow Fluid cm. per 3 min. c.c. Saline Saline *8 Alkali Alkali Acid Acid Two readings are also given in this table for comparison as in Table III. The inflow was constant. The regular step-like character of the outflow showed that the sphincter remained closed between the systoles of the antrum. If the rates of inflow were increased, a greater amount of fluid, as has been previously pointed out, was ejected at each contraction. With high rates of inflow, the step-like character of the outflow curve was lost, indicating that the outflow continued, though usually at a diminished rate during

8 134 B. A. McSWINEY AND L. N. PYRAH. the diastole of the antrum. With viscid solutions, the outflow curve, as might be expected, was not as clean cut as for other solutions. It must be emphasized that in no instance was the passage of fluid from the antrum to the intestine influenced by the type of solution. In some experiments, however, an increase in the frequency of antral contractions was recorded with the different inflow fluids. DIscusSION. By the use of the isolated pyloric antrum preparation with intact nerve and blood supply, as described in this paper, it is possible to demonstrate that the movements of the pyloric antrum and pyloric sphincter are related. Criticism may be advanced that by the introduction of a valve between the reservoir and pyloric antrum, the condition of the antrum becomes abnormal. In preliminary experiments the valve was omitted, and results similar in all details were obtained, but the amount of fluid ejected from the antrum with each contraction varied considerably. It will be realized that in the normal stomach as digestion proceeds, the stomach becomes more tubular and the prepyloric sphincter is definitely formed [Cathcart, 1911]. Indeed, with a barium meal it is possible to see the antrum full of barium apparently completely separated from the remainder of the stomach. The valve was therefore introduced to imitate the effects produced by the prepyloric sphincter. We are able to confirm the previous observations of Wheelon and Thomas [1920, 1922] that the movements of the antrum and sphincter are related, but we disagree with the statement that while the antrum is finishing its contraction, the sphincter begins its positive phase and reaches the height of its contraction when the antrum is rapidly relaxing or is relaxed. Our results show that the pyloric sphincter is normally contracted, as can be seen from the step-like form of the outflow record. Following the contraction of the antrum, the sphincter relaxes and returns to its state of contraction in some -6 sec. The relationship between the contraction and relaxation of the sphincter depends mainly on the rate of antral contraction. According, however, to Wheelon and Thomas, the sphincter is usually relaxed and only contracts for a period following the antral contraction to act as a barrier to the regression of chyme during the presence of a positive phase of the duodenum. It is extremely difficult to see how the stomach could hold fluid if the normal state of the sphincter were relaxation. The rhythmic contractions of the pyloric sphincter recorded by Wheelon and Thomas are, in our opinion, due

9 REGULATION OF THE PYLORIC SPHINCTER. 13 at least in part to the stretching of the muscle fibres by the insertion of a balloon. For in the animal, as in isolated preparations, stretching of the muscle fibres acts as a stimulus for rhythmic contractions. It has also been possible to demonstrate that the different solutions employed have little or no influence upon the pyloric sphincter when allowed to flow into the antrum. It has been pointed out that acid solutions are stated to empty at a slower rate than neutral and alkaline solutions at a rate between acid and neutral solutions. Again, Carnot and Chassevant [190] have shown that the rate of emptying of hyperand hypotonic solutions of glucose increased as the solutions approached isotonicity. Magee and Reid [1931] and McSwiney and Spurrell Fig. 3. Diagram to illustrate the relation between (P) contraction of the pyloric antrum, and (S) the relaxation of the pyloric sphincter. [1932] have also suggested that osmotic pressure of the stomach contents may prove to be an important factor in regulating the emptying of the stomach. As the pyloric antrum and the sphincter are, according to our experiments, insensitive to factors which other authors state either increase or decrease the emptying time of the whole stomach, it follows that the body of the stomach must react by increase or decrease of tone according to the fluid or foodstuff it holds. It is interesting to note the similarity which exists in some respects between the pyloric antrum and the right or left ventricle, as is evidenced by the rhythmicity of the antral contraction, the variation in height of contraction with diastolic filling, and the increase in outflow with corresponding increase in inflow. On the other hand, variation in inflow causes little or no change in the frequency of contraction.

10 136 B. A. McSWINEY AND L. N. PYRAH. SUrMARY. Experiments are described in this paper which demonstrate the relationship between the movements of the pyloric antrum and sphincter in regulating the passage of fluid from the stomach to the duodenum. The fluid was expelled from the antrum through the sphincter in spurts which synchronized with the antral contraction. The sphincter, as judged by the outflow from the pyloric antrum, is normally contracted, and relaxes some 2-4 sec. after onset of the antral contraction for a period of some 6 sec. Acids, alkalis, hypo- and hypertonic solutions and solutions of different organic acids have little or no influence on the pyloric sphincter when allowed to flow into the antrum. The height of antral contraction and the outflow of the antral contents were found to vary with the inflow. The expenses of this investigation have been defrayed in part by a grant from the Government Grant Committee of the Royal Society. REFERENCES. Alvarez, W. C. (1928 a). Mechanic8 of the Digestive Tract, 2nd ed., p Heinemann. Alvarez, W. C. (1928 b). Ibid. p Babkin, B. (1931). Personal communication. Cannon, W. B. (1907-8). Amer. J. Phy8iol. 20, 283. Carnot, P. and Chassevant, A. (190). C.R. Soc. Biol. Pari8, 7, 173. Cathcart, E. P. (1911). J. Physiol. 42, 93. Ducchesi, U. (1913). Luciani's Human Phy8iology, 2, 181. London. McCrea, E. D. and McSwiney, B. A. (1926). Ibid. 61, 28. Magee, H. E. and Reid, E. (1931). J. Phy8iol. 73, 163. McSwiney, B. A. and Spurrell, W. R. (1932). Personal communication. Wheelon, H. and Thomas, J. E. (1920). J. Lab. Clin. Med. 6, 124. Wheelon, H. and Thomas, J. E. (1922). Amer. J. Phy8iol. 9, 72.