slower than in the intact animal.

Transcription

1 66 J. Physiol. (I949) II, I2*337 THE DECREASE IN FREQUENCY OF CONTRACTION OF THE JEJUNUM AFTER TRANSPLANTATION TO THE ILEUM BY D. M. DOUGLAS From the Wilkie Surgical Research Laboratory, Department of Surgery, University of Edinburgh (Received 21 March 1949) The observation that the rhythmic contractions of the jejunum of the dog occur at a higher rate than those in the ileum was made eighty years ago by Legros & Onimus (1869). It was not until forty-six years later that Alvarez (1915) emphasized that the rate of rhythmic contraction of any segment of the small intestine of the rabbit varies inversely with its distance from the pylorus. He also noted that, in excised segments of rabbits' intestine contracting in a saline bath, the differences in rate persist, but at a frequency some 25% slower than in the intact animal. The findings of Alvarez in the rabbit were confirmed in the dog by Castleton (1934), and by Douglas & Mann (1939), who found that the rate of rhythmic contraction is constant for any given segment of intestine over long periods, and is unaffected by feeding, fasting or sleep or by section of the extrinsic nerves. The rate of contraction of the duodenum of the dog is similar to that of the jejunum and as constant (Douglas, 1948). The small intestine of dogs appears to respond to increased work, not by an increase in the rate of contraction, but by increase in the amplitude and vigour of the contractions. In the course of another investigation it was necessary to transplant a segment of jejunum of the dog to the lower ileum, and to study the rates of rhythmic contraction before and after transplantation. The pre-operative rate had been between seventeen and eighteen contractions per min.; after transplantation it fell to about twelve contractions per min.-a rate similar to that found in the ileum. This result was so unexpected that it was decided to investigate the cause of the fall in rate. METHODS Two lines of investigation were followed: (1) long-term observations were made in surviving animals with exteriorized loops of jejunum, and (2) acute experiments were carried out in anaesthetized animals with the intestine exposed in a saline bath. Dogs were used throughout.

2 RATE OF JEJUNAL CONTRACTION 67 Survival experiments In ten dogs, a loop of jejunum 5 cm. distant from the pylorus was e'xteriorized and enclosed in a bi-pedicled tube of skin according to the method described originally by Biebl (193) (Fig. 1). The following points were found to be important in the surgical technique: (a) Bitches are more suitable than dogs because of their lax abdominal skin and the absence of the penis. (b) The skin incisions should be at least 5 cm. apart to provide a tube of skin wide enough to cover the loop without tension. (c) Mobilization of the abdominal skin down to the flanks is essential to allow the abdominal incision to be closed easily. (d) In addition to the skin sutures, interrupted sutures of fine silk (.17 mm. in diameter) should be inserted at intervals of -5 cm. in the stout subcutaneous layer, to prevent dehiscence of the skin round the exteriorized loop of intestine and the consequent risk of an intestinal fistula. Fig. 1. Diagram of bitch with exteriorized loop of jejunum enclosed in bi-pedicled tube of skin. Plan of the 8urvival experiments. After recovery from the exteriorization operation, the animals were trained to lie on a padded observation table, and the activity of the intestine was recorded from day to day by an air displacement system (Douglas & Mann, 1941). Throughout this preliminary observation period of 3-5 weeks, the mean rate per minute of the rhythmic contractions was established for each loop. Each animal was then submitted to a second operation designed to elucidate the effect of various types of section of the intestine on the contraction rate of the exteriorized loop. After recovery from this operation, the day to day observations on the activity of the loop were continued for a period of 5-12 months. The various operations were as follows (Fig. 2): (a) Transplantation of the jejunal loop to the lower ileum-two animals (Fig. 2B). (b) Isolation of the loop, both ends being brought out through stab wounds in the flank as in the preparation of a Thiry-Vella fistula-two animals (Fig. 2C). (c) Section and re-anastomosis of the intestine 15 cm. proximal to the loop-three animals (Fig. 2D). (d) Section and re-anastomosis of the intestine 15 cm. distal to the loop-two animals (Fig. 2E). (e) Hemi-section and resuture of the intestine 15 cm. proximal to the loop-one animal (Fig. 2F). 5-2

3 68 D. M. DOUGLAS Acute experiments Nineteen dogs were used in the acute experiments. They were anaesthetized with pento-barbitone in doses of 25 mg./kg. intravenously. An endotracheal catheter was then passed and a light plane of anaesthesia maintained with ether. Morphine sulphate administered in 4 mg./kg. doses intravenously was found to promote active contractions of the intestine. The spinal cord was exposed by laminectomy in the upper thoracic region and divided at about the second thoracic segment. A malleable wire was then passed down the theca to the sacral region, vigorously rotated, and withdrawn, destroying the cord below the level of section; the central connexions of the sympathetic supply to the intestine were thereby destroyed. At this point it was found expedient to institute controlled respiration with a positive insufflation pump (stroke volume 15 c.c., rate 25/min.). The abdomen was opened by a midline incision; one balloon was placed in the descending part of the duodenum and another in the upper jejunum at a measured distance A B C D E F Fig. 2. Diagram of the various operations performed on the jejunum. A, the exteriorized loop; B, loop transplanted to lower ileum; C, loop isolated; D, section and re-anastomosis proximal to the loop; E, section and re-anastomosis distal to the loop; F, hemi-section and resuture proximal to the loop. from the pylorus. In five of the experiments, the vagi were severed as they lay on the abdominal part of the oesophagus. The whole animal was then placed in a constant temperature saline bath maintained at C, The balloons were connected to water manometers and inflated to a pressure of 2 cm. of water; the movements of the water in the manometers were recorded by a kymograph. After a control tracing lasting 2-3 min., one of the following manipulations was performed on the bowel midway between the balloons: (a) An intestinal clamp was applied crushing the gut. (b) The wall of the bowel was infiltrated with i% procaine hydrochloride. (c) The bowel was completely severed. After these interventions the tracing was continued for 1-2 hr. In order to demonstrate the effect of these manoeuvres on the rate of the rhythmic contractions it was essential that there should be active and regular contractions in both duodenum and jejunum simultaneously. This proved to be the chief difficulty of the method, since, although the duodenum was usually active, the jejunum was often quiescent. In overcoming this difficulty it was found of value to allow 2-3 hr. to elapse between destruction of the cord and the making of the

4 RATE OF JEJUNAL CONTRACTION 69 intestinal tracing, and to use a shallow plane of ether anaesthesia, relying on the morphine sulphate for supplementary sedation. At the end of the experiment the dogs were painlessly killed while under the anaesthetic. The tracing was then fixed, ruled off in intervals of 1 min. and the number of rhythmic contractions per minute counted. RESULTS Survival experiments (Table 1) Control period. In the ten dogs with exteriorized jejunal loops, in the control period, the contraction rate was relatively constant for each animal. There was also little variation from dog to dog, the slowest mean rate being 17x1 contractions per min. and the highest TABLE 1. The effect of various operations on the rate of contraction of segments of exteriorized jejunum in surviving dogs. The figure following the mean is the standard error of the mean and the figure in brackets the number of observations upon which the mean is based Mean rate of Mean rate of contractions/min. contractions/min. Mean Dog Control Operation Post-operative difference 1 17*6±-12 (46) Transplantation to ileum 12-1±-5 (125) ±-13 (51) Transplantation to ileum 15-3±-5 (168) ±.8 (53) Isolation 12-3±-8 (84) ±-9 (76) Isolation 14-7 ±-8 (112) ±.7 (72) Proximal section 143 ± 5 (229) ±-8 (88) Proximal section 14-1 ± 4 (259) ±.13 (56) Proximal section 12-7 ± 7 (97) ±-7 (112) Distalsection 17-8 ±-6 (92) ±-8 (83) Distal section 17-6 ±-5 (131) ±-8 (75) Proximal hemi-section 18-2 ± 4 (288) +-1 Effect of transplantation. In both dogs transplantation of the loop to the lower ileum resulted in a fall inr the mean contraction rate, in the first by 5-6 contractions per min. (28 6 %)bnd in the second by 2-7 (12.2 %). The animals were observed for more than a year and there was no return to the original rate. Effect of isolation. In both animals in which the loop was isolated with the nerve and blood supply intact, a similar fall in rate occurr"ed, of 5-2 and 3-1 contractions per min. respectively (28 and 17-4 ). Effect of proximal section. The operation of section and re-anastomosis of the intestine 15 cm. proximal to the exteriorized loop resulted in a fall --in the contraction rate of the loop in all three animals by 3.4, 4-2 and 5-4 contractions per min. (19.2, 23 and 27 %) respectively (Figs..3 and 4). Recovery in rate has not taken place 9 months after operation. Effect of distal section. In contrast to the effect of the above operations, section and re-anastomosis of the intestine 15 cm. distal to the loop was not followed by a change in contraction rate in either of the two animals in which the operation was carried out (Fig. 5).

5 7 D. M. DOUGLAS E z A * Time (weeks) Fig. 3. Mean rate of contraction of jejunal loop. Ordinates: mean rate of contractions per min. Abscissae: time in weeks from original observation. At arrow, the operation of proximal section and re-anastomosis. The fall in mean rate should be noted. Fig. 4 Contractions of exteriorized jejunal loop. Upper tracing, control period. Lower tracing, after proximal section and re-anastomosis. Time in minutes. The fall in rate can be seen, and the frequency is shown above each record.

6 RATE OF JEJUNAL CONTRACTION 71 Effect ofproximal hemi-section. In order to observe the effect of an operation of comparable severity on the intestine proximal to the loop, which did not involve complete interruption of continuity, the antimesenteric half of the circumference of the intestine was divided and resutured in one animal. This operation was not followed by a change in contraction rate. Acute experiments Application of clamp. In seven experiments in this group a clamp was applied between duodenum and jejunum (Table 2). A fall in the frequency of rhythmic contractions in the jejunum occurred in all the experiments, while the frequency of the duodenal contractions remained unaltered. The onset of the slowing was usually immediate. The mean fall in the seven experiments was 2-9 beats per min * 16 *.. VI 5 IE Z ~~~~~ Time (weeks) Fig. 5. Mean rate of contraction of jejunal loop. Ordinates: mean rate of contraction per min. Abscissae: time in weeks from original observation. At arrow, the operation of distal section and re-anastomosis. The mean rate is unaltered. After removal of the clamp, recovery of the rate of contraction to the original level occurred in three of the experiments. In the remaining four, the jejunal contractions did not regain their original rate. Injection of procaine hydrochloride. In ten experiments the wall of the intestine, midway between the two balloons, was infiltrated in a 'ring' fashion with 1 c.c. of 1 % solution of procaine hydrochloride. Slowing of the jejunal rate was noted in each experiment in this group, the mean fall being 3* beats per min. (Figs. 6 and 7, and Table 3). DISCUSSION Reference to an investigation on the effect of transplantation of segments of intestine on the contraction rate has not been found in the literature, though Castleton (1934) isolated segments of jejunum and divided their mesentery. He found that this operation caused a fall in rate of about 25 %.

7 72 D. M. DOUGLAS C3N r- ld to O-4 '4Q ~ "? O C 1+.2 o _~ 54a) Pa4 C)P 4 - b M CB Co 6 eq eqesq _ *_O _ eq eq -H_H-H H _H - C COOO -H -H4 i-h -H -H t Z -to- Ca XI da) d * ro Ca QOa C) Ca,,d I I-- c-1 c-1 - eq - eq c - C' Ct C4i CO CA Ci CO C *-H-H -H+H +HH -- -H -H-H -H -H M - a to C ---- a1mlo R IR U:COa)e co gooooooooo&~ P Io M tto M M w t *gh -H++H+-H-H I-- a)s E-4 Q co W oa) "4. oi" co C)4 4 a) bid.5 P4 CB- C)I pq. a) V _ ō Cxo t ~ I eq 6 e ecb tq b -t_oci._ Xo Mo o o o t- ab cb'c t's: ' P- r- r- P-,- - -.) $M4 4 5 v b* J o -4o o -4a w._ C) 4-4.)> M w '4._ 4a)d P.) a) q - r- - - eq to ) M -eqc -o-o r o o - eq M " H -HH H --H -H-H P O _ EelCOOC CO e _- _ C-----$-- eqm V olo o- xo -fl-h-- -HH -fl -- -H-H -H * C> El-H -f4 -H-H-H-H ~~ a) ) k MakOe I M M * xo xo Ez~~~~~~~~~~~~~~~~~~~~~~~~~l XX C t n n COt:45 ec a2~~~c Cs a a ~ o4

8 RATE OF JEJUNAL CONTRACTION 73 Fig. 6. Contractions of duodenum (D) and jejunum (J) in acute experiment. Time in minutes. At arrow, 1 c.c. of i% procaine hydrochloride injected round intestinal wall between the balloons. The duodenal rate is unaltered while the jejunal rate falls. 18- C. E u v z 17 O 16- El Mr 13 o oo ) is- M l = Duodenum 1 E1 l m El 12 E=Jejunum E ElE 11 1 I I I I I I I Time (min.) Fig. 7. Rate of contraction of duodenum and jejunum in acute experiment. At arrow, 1 c.c. of i% procaine hydrochloride injected round intestinal wall between the balloons. The duodenal rate is unchanged while the jejunal rate falls.

9 74 D. M. DOUGLAS Mann & Watkins (1948), in a personal communication, write that they have transplanted loops of jejunum to the ileum in the dog, and found a fall in rate of an order similar to that reported in this paper. The problem for solution at the outset of this study was why transplantation of a loop of jejunum, with nerve and blood supply intact to lower ileum, should cause a fall in the rate of contraction. The results of both the survival and acute experiments suggest that it is due to division of the intestine proximal to the loop. This step is common to the operations of transplantation and isolation of the segment, and is the only significant operative measure in the operation of proximal section and re-anastomosis. In the acute experiments the injection of the local anaesthetic caused slowing distal to, but never proximal to, the point of infiltration. The only explanation which appears to fit these facts is that normally the rhythmic activity of the duodenum and jejunum is co-ordinated. When the intestine is transected and re-anastomosed, union takes place by the formation of inexcitable fibrous tissue, and the process of rhythmic excitation cannot then be transmitted to the jejunum. The latter therefore takes up its inherent rhythm in much the same way as do the ventricles when cut off from the atria by division of the bundle of His. The connexion between atria and ventricles co-ordinates the activity of the heart so that the heart may act as an efficient functional unit. It may be suggested that the rhythmic activity of duodenum and jejunum are similarly co-ordinated so that they may act as a physiological unit as far as motility is concerned. It is of interest that the type of contraction observed in both the duodenum and jejunum consists for the most part of propulsive waves occurring at a rate of per min. The contractions of the ileum are different; they occur at the slower rate of per min. and commonly have the characteristics of segmentation, that is of alternate contraction and relaxation of adjacent segments without any obvious propulsive properties. These differences in type of contraction are reflected in the different rates of transit of food residues. A barium meal passes more quickly through duodenum and jejunum than through ileum (Shanks, Kerley & Twining, 1938). The slower rate of progress of food residues through the ileum may be related to absorption in the ileum of the chyme which has been thoroughly digested in the more cranial part of the intestine. It is of interest that Keith (1915) suggested that in the small intestine of the rat there were several rhythmo-genic centres composed of tissue similar to that of the sino-atrial node. He believed that these centres might act as pacemakers for adjacent segments of intestine.

10 RATE OF JEJUNAL CONTRACTION SUMMARY 1. Segments of jejunum, in continuity and with nerve and blood supply intact, were exteriorized and enclosed in bi-pedicled tubes of skin in ten dogs. 2. The rate of rhythmic contraction in a control period of 3-5 weeks was constant in each segment and showed little variation from animal to animal. 3. Transplantation by end-to-end anastomosis of the exteriorized segment to the lower ileum was followed by a fall in rate which persisted for at least a year after operation. 4. A similar fall in rate was seen after isolation of a segment or after transection of the bowel and re-anastomosis proximal to it. A change in rate did not occur after transection of the bowel and re-anastomosis distal to the segment or after hemi-section of the bowel proximal to it. 5. In acute experiments, infiltration of the wall of the intestine with I% procaine hydrochloride solution was followed by a fall in contraction rate distal to the point of infiltration but by no change proximal to it. Clamping and transection of the bowel had the same effect. 6. These results are taken to suggest that the rate of contraction of the jejunum is influenced by the duodenum. REFERENCES Alvarez, W. C. (1915). Amer. J. Phy8iol. 37, 267. Biebl, M. (193). Klin. W8chr. 9, Castleton, K. B. (1934). Amer. J. Phy8iol. 17, 641. Douglas, D. M. & Mann, F. C. (1939). Amer. J. dig. Di&. 5, 318. Douglas, D. M. & Mann, F. C. (1941). Brit. mied. J. i, 227. Douglas, D. M. (1948). J. Phy8iol. 17, 472. Keith, A. (1915). Lancet. ii, 371. Legros & Onimus (1869). J. Anat., Paris, 6, 37. Mann, F. C. & Watkins, D. (1948). Per8onal communication. Shanks, S. C., Kerley, P. & Twining, E. W. (1938). Textbook of X-ray Diagno8i8. London: H. K. Lewis. 75