it by the sympathetic nerve.

Transcription

1 OBSERVATIONS ON AUGMENTED SALIVARY SECRETION. BY G. V. ANREP. * (From the Institute of Physiology, University College, London.) IN 1889 Langley described a peculiar effect of stimulation of the cerebral secretory nerves of the salivary glands upon the amount of saliva obtained by stimulating the sympathetic nerve. According to his observations made on the dog, the sympathetic nerve when it is stimulated shortly after the cranial nerve, produces a brief rapid secretion from any or all the salivary glands. A very brief stimulation of the cranial nerve is sufficient to produce this effect. The augmenting effect disappears in time, although the sympathetic is not stimulated in the interval. If the sympathetic is stimulated for a longer time or several times in succession the effect is found to disappear quickly, and, as a rule, the third or fourth stimulation is already ineffective. Atropine in doses sufficient to paralyse completely the-cranial nerve paralyses its augmenting action. Direct measurements of the blood flow through the gland as well as the fact that atropine paralyses the augmenting action of the cranial nerve led to the conclusion that mere vascular dilatation is not the cause of the augmented secretion. Langley explains it by a transitory increase in the irritability of the gland to impulses reaching it by the sympathetic nerve. In the course of a series of experiments withf the salivary glands performed for a different purpose I had frequent opportunities to observe the facts described by Langley. And my observations were in every detail in complete accord with Langley's. In this communication only,those experiments are described which deal with the explanation of the augmented secretion and which suggest that its cause is probably different from the one advanced by Langley. The effect of filling the ducts of the salivary gland. All experiments were performed under morphia and c.e. mixture or under chloralose, the latter being injected intravenously in doses 0075 or 01 per kilo. Exp. 1. Dog 8, 2 kg. Chloralose. Cannula in the right submaxillary duct. The right chorda tympani and the right vago-sympathetic nerve cut and prepared for stimulation. The salivary cannula is joined with a glass tubing of narrow bore fixed to a millimetre scale, each 45 mm. of the tubing being equal to 0-2 c.c. The secretion is noted every 30 seconds unless otherwise mentioned.

2 264 G. V. ANREP. (1) Time Secretion in mm.: 0, 0, stim. vago-symp. (coil = 12) 0, 0, 0, 0, chorda for 15' (c = 14) 24, 10, 0, 0, 0, 0, v-s. 30' (c = 12) 20, 1, 0, 0, v-s. 3, 0, 0. (2) , 0, saliva forced back into the gland by blowing into the tube connected with the duct; backwards 22, 0, 0, 0, v-s. 30' (c = 13) 18, 2, 0, 0. (3) , 0, v-s. 30' (c = 13) 0, 0, 0, 0, saliva backwards 20, 0, 0, 0, v-s. 30' (c = 13) 18, 1, 0, 0. (4) , 0, saliva backwards 25, 0, 0, 0, 0, v-s. 30" (c = 13) 22, 2, 0, 0, 0, three min. no secretion. Chorda 30" (c = 16) 36, 13, 0, 0, 0, v-s. 30' (c = 13) 20, 2, 0, 0, five min. interval, 0, 0, saliva backwards 23, 0, 0, 0, v-s. 30' (c = 13) 20, 1, 0, 2, 0, 0, 1, 0, 0, 0, 0, 0. This experiment shows that the augmented secretion is obtained equally well after some saliva is forced in a purely mechanical way backwards into the gland as after a previous stimulation of the cranial nerve. The time of the complete disappearance of this effect is in both cases the same, it generally varies between 10 and 18 minutes. In no case has there been found any addition of saliva to the amount pressed into the gland, which shows that no actual sympathetic secretion took place. The effect of atropine. This was tried as follows: Exp. 2. Dog 7, 8 kg. Preparation as in the previous Exp. but the sympathetic fibres stimulated above the superior cervical ganglion. (1) , 0, chorda (c = 15) 15' 26 15', 5, 0, 0, 0, sy. 30' (c = 13) 14, 0, 0. (2) , 0, saliva backwards 25, 0, 0, 0, sy. 30' (c = 13) 21, 0, 2, 0, 15 mgm. of atropine sulphate injected intravenously. (3) , 0, chorda 30' (c = 12) 0, 0, 0, 0, 0, 0, 0, 0, sy. 30' (c = 12) 0, 0, 0, 0, 0, 0, saliva backwards 25. 0, 0, 0, sy. 19, 0, 0, 3, 0, 0,1, 0, 0, 0, 0, 0. (4) , 0, sy. 1, 0, 0, 0, 0, 0, saliva backwards 32, 0, 0, 0, sy. 25, 2, 0, 0, 4, 0, 0, 1, 0, 0, three min. interval 0, 0, saliva backwards 29, 0, 0, 0, sy. 20, 0, 6, 0, 0, 2, 0, 0. Atropine does not paralyse the effect of forcing the saliva into the gland upon the subsequent stimulation of the sympathetic nerve, but it does paralyse the augmenting action of the chorda. It seems, therefore, that the essential factor in the augmented secretion is not the stimulation of the chorda but the filling of the gland with saliva by whatever means. The effect of the sympathetic upon the ducts of the gland. To determine whether the augmented secretion could be explained by a constriction of the ducts the following experiments were performed: Exp. 3. Dog 9, 2 kg. The nerves prepared as in Exp. 2. The salivary cannula was joined with a burette filled with warm gum-saline solution. The pressure of the fluid was kept constant at 35 cm. In 30 min. only 1-2 c.c. of fluid was absorbed by the gland. At the end of this period the gland itself looked quite normal and without cudema. The burette was now clipped off from the gland and several incisions were made in the gland with sharp scissors. All the incisions were superficial only. The bleeding surface of the gland was mopped with wool and in about a quarter of an hour the bleeding stopped. The clip was then removed and the gland was again connected with the burette. The gumsaline now ran freely into the gland and out through the incisions. The amount of fluid passing through the gland was noted every 30' by reading the burette.

3 AUGMENTED SALIVARY SECRETION. 265 Fluid passing through the gland in c.c. per 30 sec. (1) , 1, stim. sy. 30' (c= 16) 5, 1, 1, 1. (2) , 1, sy. 15' (c = 14) 3, 1, 1, 1. (3) l1, 11, sy. 30' (c=12).1,.3, 1, 1. (4) , 1, sy. 30' (c=15) 3, 5, 1, 1. (5) , 1 1, sy. 60' (c=12) 1,0, 0, 3, *6, 1, 1 1, mgm. of atropine injected intravenously. (6) , 1, sy. 30' (c=12) *2, *2, -5, 1, 1. (7) , 1-3, 1*3, 1*3, sy. 30' (c=12) 15' *2 15 0, in 30', 0, 6,.9, 1-3, 1-3. The diminution in the flow cannot be explained by a blockage of the ducts by a viscid sympathetic saliva on the following grounds: the sympathetic secretion in the dog is extremely small; one would have to suppose a balance between the viscosity of the saliva and the pressure of the fluid; it would not be expected that the perfusion should start so quickly after the end of the stimulation. After the end of the experiment the gland looked quite normal. In order to test whether all the perfusion fluid passed through the gland the following determinations were made. Two pieces of cotton wool were weighed. The first of them was applied for 30" to the previously dried surface of the gland, the perfusion being stopped. The increase in weight was taken to represent the amount of exudation from the damaged surface of the gland. The second piece of wool was applied in the same manner but with the perfusion on. The increase in weight represented the amount of fluid which passed through the gland in 30" together with the exudation. Comparing the weights of the fluid which entered the gland with that which left it a conclusion could be made as to whether absorption or secretion took place. As an example the following figures may be quoted: Increase in weight of the wool with perfusion 1-32 gr.,,.9,, 9 without,, 015, Perfusion fluid leaving the gland *17,,,, which entered the gland ,, A few determinations of this kind were performed during the stimulation of the sympathetic nerve. The first column gives the figures obtained without the stimulation, the second during the stimulation. Increase in weight Gr. Gr. Transudation and perfusion in 30' Transudation alone in 30' Difference representing outflow 1l Inflow from the burette

4 266 G. V. ANREP. On several occasions the stimulation of the atropinised chorda was tried but this was not found to have any effect on the rate of the perfusion of the gland. Exp. 4. Dog 9, 4 kg. Chloralose. Preparation as in Exp. 2. The level of the saliva in mm. is noted every 30'. Eight mgm. of atropine were injected half an hour before the first reading. The chorda was completely paralysed. Tube horizontally, saliva stays for 8 min. at 320 mm. Tube placed vertically-saliva slowly runs down into the gland and soon takes a new level at 280 mm. No movement of the saliva for 2 min. (1) , 280, sy. 30' (c = 12) 298, 296, 285, 280, 280. (2) , 280, sy. 30' (c= 11) 301, 302, 298, 283, 280, 278, 278. (3) , 278, sy. stim. at figures in thick type (c = 12) 301, 301, 303, 300, (c = 11) 312, 310, 315, -, -, 300, 316, 310, 305, 294, 285, 285. Some saliva ran out, new level at 222 mm. (4) , 222, sy. stim. for 5 min., the maximal level is reached (c = 11) in 2 min'. at Stimulation stopped-saliva falls and in 5 min. reaches 222. Massage of the gland -maximal level 275, massage stopped-saliva down to 222. Massage of the gland, saliva rises to 275, prolonged stimulation of the sympathetic directly after the massage-saliva down to 256 where it remains stationary during the stimulation. In 2 min. the stimulation is stopped and the saliva soon comes back to 223. Exps. 3 and 4 indicate that the stimulation of the sympathetic nerve produces a diminution of the capacity of the ducts of the submaxillary gland. In Exp. 3 with the perfusion of the gland it caused a diminution of the flow of the fluid through the gland. In Exp. 4 it developed a pressure within the ducts. The last experiment cannot be explained by a sympathetic secretion as no progressive rise of the saliva was observed with each successive stimulation. Massage of the gland. Massage of the submaxillary gland after a previous chorda stimulation h,as a variable effect. At the beginning of an experiment only very little saliva can be pressed out, If some saliva is pressed back into the gland it likewise cannot be pressed out by massage. The effect of massage does not alter after protracted stimulation of the chorda so that the retention of the saliva cannot be due to blocking of the ducts by a viscid fluid. In some dogs, however, especially in those which were kept for a long time under anaesthetic, the effect of massage became more and more marked and a large amount of saliva could be pressed out of the gland after every chorda stimulation. Saliva which has been forced into the gland does not stay in it, but slowly flows out, and by means of some mechanical pressure on the gland it can be completely pressed out. The augmented secretion does not disappear and in some experiments it is still larger than the effect of massage, in others, massage has been found more effective than the stimulation of the sympathetic.

5 AUGMENTED SALIVARY SECRETION. 267 Exp. 5. Dog 8, 5 kg. Preparation as in Exp. 1, but the secretion is recorded in drops (1 c.c. =70 drops). No. of drops No. of drops (1) 4.55 chorda 60' 13 (2) 5.22 chorda 60' 12 interval 30 2 interval 90 4 massage v-symp v-symp interval 30 1 massage 60 1 massage 60 (3) 5.22 massage 60 2 (4) 5.36 chorda interval, 0 interval massage,, 2 v-symp interval,, 0 interval,, 2 v-symp.,, 1 massage,, 1 interval,, 0 interval,, 0 v-symp.,, 2 v-symp.,, 1 interval,, 0 interval,, 0 massage,, 2 (5) 5.55 chorda interval 60 3 (6) 6.12 chorda massage interval v-symp v-symp massage 60 0 massage 60 1 In this particular experiment the stimulation of the sympathetic nerve produced a bigger effect than massage. In several other experiments, however, the action of the sympathetic was much weaker than massage. In those experiments the augmented secretion was also very weak. Exp. 5 indicates that during the augmented secretion there is only an emptying of the ducts from stagnant saliva but not an actual secretion. The amount of saliva obtained from the gland by massage with a following stimulation of the sympathetic is approximately the same as the one obtained by the stimulation of the sympathetic without a previous massage. In the above experiments the figures are 16, 20 and 23 drops as against 14, 19 and 24 drops. In each case the stimulation of the sympathetic was continued much longer than the secretion so that a still longer stimulation would not cause any more secretion. Massage of the gland after a sympathetic stimulation does not cause any flow of saliva, which suggests that the gland is empty. Two experiments were performed with the use of ergotoxine; in the first ergotoxine was injected intravenously, in the second the gland was perfused with a solution of ergotoxine in gum-saline. The blood flow through the gland was recorded at the same time as the secretion. In both experiments it was found that the augmented secretion was paralysed with far smaller doses than the vaso-constrictors. The experiments with ergotoxine support Langley's statement that the augmented effect is independent of the vascular condition of the gland. Langley found the augmented secretion in the parotid gland of the dog and in the sub-

6 268 G. V. ANREP. maxillary of the cat to be much less marked. In accordance with this a few experiments performed with perfusion of those glands showed a much smaller effect of the sympathetic on the rate of flow of the fluid through the gland as compared with the one described for the submaxillary gland. CONCLUSIONS. 1. No support is given to the explanation of the "augmented secretion" being due to an increased irritability of the salivary gland to impulses reaching it by the sympathetic nerve. 2. The suggestion is put forward that the augmented effect of the sympathetic is an emptying of the gland of stagnant saliva caused by a narrowing of the ducts either due to their own contractility or due to a contraction of tissues around the alveoli and the ducts. 3. The most probable explanation of the disappearance of the augmented effect is the absorption of the saliva from the ducts and alveoli. The expenses of this research were defrayed by a grant from the Medical Research Council. REFERENCE. Langley. This Journ. 10, p