University College, Cork.)

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1 THE FUNCTIONS OF THE GREAT SPLANCHNIC NERVES. BY D. T. (From the Department of Physiology, BARRY. University College, Cork.) "ON no subject in physiology do we meet with so many discrepancies of fact and opinion as in that of the physiology of the intestinal movements." This statement made by Bayliss and Starling in 1899 holds a lot of truth as applied to our knowledge of the subject at the present time. Nobody can state with precision what the functions of the great splanchnic nerve are in relation to intestinal or other activity. Contractile fibres to the spleen have just been demonstrated in this nerve by B a r croft and his associates [1932], and it is certain that its role in vascular and intestinal reactions needs further investigation and definition. Having observed several irregularities of response while investigating with A. and B. Chauchard [1932] the variations of splanchnic chronaxie due to bleeding, etc., I determined to test the possibility of ascertaining something definite about splanchnic function by splitting the nerve into two or more bundles, so as to dissociate different activities in stimulating the separate branches. If one could approach the problem by artificially separating the different groups of fibres and stimulating the bundles individually and collectively some further light might be thrown upon it. Strict isolation of each strand of fibres corresponding to each function was not hoped for, but a preponderance of a certain function was expected to be exhibited by a given bundle. METHOD. The animals used in these experiments consisted of twelve dogs and four rabbits. They were always fully chloralosed. The great splanchnics were dissected out and cleaned on both sides. They were then cut as high as possible without injury to the diaphragm. The right nerve demands a good deal of care. Both nerves require to be cut in order to get good intestinal movement. The viscera were interfered with as little as possible. In some experiments both nerves were split longitudinally

2 FUNCTIONS OF GREAT SPLANCHNIC NERVES. 481 into two parts, in others one of the nerves was split into two or three bundles. Separation into four parts was also tried and was found to be difficult; but it should be easier with improved technique. The rabbit's nerve was merely divided into two portions. The nerve in many instances was excited as a whole before division. The electrodes used consisted of a pair of silver wires across the lumen of a small vulcanite or glass tube about 2 in. long. On to these wires the nerve or bundle was drawn through a small opening at the lower end of the tube by means of a thread. The tube was then corked at the upper wide end, the stopper fixing the thread and holding the nerve in position. Thus the tube provided a practically water-tight chamber for the nerve. Excitation was effected both by galvanic and faradic currents, the strength varying from 4 to 6 volts in the former and the frequency from 5 or 6 to 12 per sec. Two pairs of electrodes were generally in place together, the exciting current being changed from one to the other by a switch. The reactions observed were those of the intestine, of which the movements were recorded by the balloon method, and of the bloodpressure as taken from the carotid artery. Records from the artery were obtained either by means of a Hurthle's tambour with a mercurial manometer in the system, or by the mercurial manometer directly. The position of the balloon was varied; in many instances it was placed in the upper jejunum, in others at different lower levels. Two and three balloons have been used in some recent experiments, but the results of these are not at present included. The responses of the suprarenal gland and of the spleen could also be observed, but no means of measuring these were employed. Intense contraction of the exposed spleen could be seen as a result of splanchnic stimulation. The animal was not placed in a bath, but the viscera were well covered and kept at uniform temperature by warm saline irrigation. RECORDS. Each record shown in this article is a double one of blood-pressure above and of intestinal movements below. The time represents intervals of 5 sec. On account of the occasional great excursions of intestinal records it was found simpler to get an assistant to mark with a cross the exact point of beginning stimulation than to use an electric signal. The duration of stimulation was 20 sec. unless otherwise stated. The bloodpressure was generally low with the splanchnics cut, namely from 65 to 80 mm. Hg. Figures for the different variations are not included as they can be pretty closely judged. All the records are from dogs.

3 482 D. T. BARRY. PRESENT VIEWS. The older views concerning splanchnic function were modified as a result of the work of Bayliss and Starling [1899]. The conclusions of these authors have been questioned as regards certain details, but in the main they are still regarded as truths. They say that the splanchnic nerve exerts a tonic inhibitory influence on the intestine, that excitation of the nerve causes inhibition of the longitudinal and circular fibres, while there is no evidence that these nerves ever possess a motor function. The inhibition is independent of circulatory changes. The vagus, they say, possesses two sets of fibres, inhibitory and augmentor, the former having a short latent period and the latter a long one. This vagal action, they hold, is in no way due to spread to the splanchnic. Bunch [1899] said that he obtained evidence of intestinal vaso-dilator as well as vasoconstrictor fibres in the splanchnic nerve. On stimulation of the nerve he observed vaso-constriction at first and then in some cases vaso-dilatation. The vaso-dilatation he demonstrates by intestinal plethysmographic curves, and in none of his records is there any fall of arterial pressure from splanchnic stimulation. B u n c h shows in one record a slight excitatory intestinal effect from splanchnic stimulation, but he makes nothing of it as demonstrating such fibres in the nerve. Page May [1904] mentions that several observers believe that the splanchnics contain both motor and inhibitor fibres to the stomach; the vagus also is believed to have a similar double function. Openchowski [1899] and others also attribute a double function to the gastric nerves. Gastric innervation, however, which has recently been reviewed by McSwiney [1931], is a different consideration from intestinal innervation, though prima facie one may expect some similarity of action of sympathetic and parasympathetic supplies in both cases. It is stated by Weil [1931] that a reversal of the common effects ascribed to the splanchnic may occur, and Spadolini [1917] described a pure inhibitory effect from vagal stimulation and a pure augmentor one from the splanchnic, while opposite effects were given by different parts of the gut. Alvarez [1922] says that while the vagus generally has an excitatory and the sympathetic an inhibitory action on the gut these effects are transient and vary with strength of current, condition of the muscle, etc. This author says that vagus stimulation at first causes diminution of tone, and sec. later increased activity. This corresponds in the main with the view of Bayliss and Starling, thoughalvarez questions their conclusions on other points, such for instance as the characteristics

4 FUNCTIONS OF GREAT SPLANCHNIC NERVES. 483 of the contractions. Bercowitz and Rogers [1921] have pointed out the importance of the rate as against intensity of stimulation in determining responses. This and other characteristics of excitability, chronaxie, and stimulation, are certainly important considerations. It looks as if a final solution of the problem will be reached only by thorough investigation of these features. The variations of response observed in the -present experiments as a result of alterations of the frequency of the galvanic current were not sufficiently definite to be considered as distinguishing characteristics. The most effective frequency for stimulation was found to be 10 or 12 per sec., but the lower rates were not without effect. It is a point worth further investigation. An augmentor function then is ascribed to the gastric sympathetic, but neither the authors mentioned nor others present any serious evidence to oppose the observation of Bayliss and Starling that splanchnic stimulation never gave intestinal motor effects. The chief point of the present communication being to show the occurrence of such intestinal motor effects of splanchnic excitation, I may anticipate the general statement of results by saying that an augmentor action on the contractions of the gut was frequently observed on stimulating different parts of the nerve. The variations of intestinal and vascular responses obtained on stimulating separate parts of the splanchnic nerve indicate the presence of different types of fibres in these nerves. RESULTS. The usual effect obtained from stimulation of the whole splanchnic with a galvanic current was an increase of blood-pressure consisting of an immediate primary rise and a later secondary one. Inhibition of intestinal contractions usually accompanied the vascular effect (Fig. 1). This record shows the result of stimulating in A one half (the inner) and in B the other half of the left splanchnic nerve. Stimulation of the whole nerve previously had caused a response similar to B. In both cases there is a typical immediate inhibition of the intestine; the balloon was placed about 12 in. below the duodenum. The inhibition in A is followed by strong contraction and increase of the rate of activity; in B it is followed by increased rate only. In this experiment the application of the Faradic current caused a similar reaction in each case. In other instances a difference in the action of the two currents was observed. In neither of the reactions shown in Fig. 1 is there any appearance of a secondary or adrenaline inhibitory action on the intestine, though the

5 484 D. T. BARRY. secondary increase of blood-pressure is obvious. This indirect effect of stimulation was well marked in other experiments. The differences in the responses of different bundles of fibres were sometimes very pronounced. Much depended on the nature and duration of the stimulus, but uniformity of these factors was a condition applied for comparison of the separate parts of a nerve. One advantage of the method adopted is that excitation of different strands of fibres sometimes gives quite a good dissociation of intestinal and vascular reactions; a rise of blood-pressure given by exciting one bundle may not occur, or may be reversed, by exciting another, while the intestinal response remains unaltered. This is an important factor in deciding how much of an intestinal reaction may be due to the vascular change. Fig. 1. Alternate stimulation of two bundles of left splanchnic. The effect on arterial pressure is the same, that on the intestine dlifferent. The same excitation wa-s applied at + in each case. Duration 20 seconds. In the foregoing experiment (Fig. 1) the increased activity of the gut might be said to be a natural reaction after the quiescent period, and more or less independent of nerve influence. But the augmentor effect was much more rapid in onset in other experiments. Stimulation of onethird of the right splanchnic for instance caused an almost immediate and marked increase of intestinal contractions (Fig. 2) with little or no vascular change. A minute or so later the effect had passed off, and a stronger stimulus at the second mark was applied to the same bundle. This time we have an initial period of inhibition lasting about 10 sec. and then a phase of pronounced increase of activity for about 30 sec. With this second gut reaction there occurs a definite fall of blood-pressure. The intestinal reactions following both excitations are very similar except

6 FUNCTIONS OF GREAT SPLANCHNIC NERVES. 485 for the inhibitory phase in the second; the vascular reactions are not similar. That part of the intestinal response which is simultaneous with the change of blood-pressure is the inhibitory phase. It is not for this reason to be regarded as the consequence of the fall of blood-pressure. We get inhibition much more frequently with increase of blood-pressure. The excitatory phase also seems to be quite independent of vascular change, especially.in the first reaction. In many other instances it was also quite unconnected with circulatory disturbance. Stimulation of the other thirds of the nerve under consideration caused increase of bloodpressure and inhibition of the gut. Fig. 2. Immediate increase of the gut contractions from stimulation (Faradic) of branch of right splanchnic. The second stimulus (stronger) applied to the same branch. A fall of blood-pressure occurs and again the contractions increase after initial loss of tone. The right splanchnic nerve was separated into three branches in another dog. Stimulation of one of the branches caused intestinal inhibition lasting more than half a minute, followed by great increase of activity lasting more than a minute, all with practically no vascular changes (Fig. 3). This increased phase of activity is not presented as an example of an augmentor effect of stimulation, as it may perhaps be considered explicable as an after-effect brought about locally. The interval between the end of stimulation and the beginning of the marked increase of amplitude as compared with initial contractions is about 50 sec. As a latent period this interval is too long to permit one to describe the change as a simple reaction to the stimulation of the nerve. Splanchnic bundles have been isolated stimulation of which occasioned pure inhibition of the intestine and pure hypotension in the

7 486 D. T. BARRY. i I I I I i i Fig. 3. To show intestinal inhibition from branch stimulation without blood-pressure change. The late increased activity of the gut to be compared with the quick response in Fig. 2. Stimulation 12 secs. Fig. 4. Branch stimulation causing fall of blood-pressure and of intestinal tone. (Right splanchnic.) circulation (Fig. 4). In this record no secondary increase of activity is shown by the intestine, rather a secondary loss of tone is seen which may be ascribed to adrenaline, though no influence of this is observed on the

8 FUNCTIONS OF GREAT SPLANCHNIC NERVES. 487 pressure curve. Obviously there existed hypotensive and intestinal inhibitor fibres in the branch of nerve excited, and the stimulus (Faradic) was appropriate for both. Faradic stimulation of the other branch of this Fig. 5. Tonic effects of splanchnic stimulation; secondary coil at 12 cm. and at 7 cm. Fig. 6. Showing three phases of splanchnic influence on the intestine. Direct inhibition, increase of tone and adrenaline effect. nerve caused a small rise of blood-pressure and inhibition of the gut. No augmentor intestinal effect was obtained, but that does not essentially mean that the nerve contained no augmentor fibres. In the first branch mentioned practically all forms of excitation elicited some inhibition but not hypertension.

9 488 D. T. BARRY. When the natural movements of the gut are small there is frequently another type of augmentor reaction, namely a peristaltic or prolonged increase of tone (Fig. 5). The duration of the change in this record coincides with that of the blood-pressure where stimulation was strong. The secondary coil was at 12 cm. distance in the first excitation and at 7 cm. in the second. This peristaltic reaction may also exhibit a preliminary inhibitory phase (Fig. 6); here a falling off in tone occurs when the secondary increase of blood-pressure is pronounced. These variations all indicate much independence of intestinal activity in relation to vascular conditions. A mixed reaction has also been observed, that is one in which a strong peristaltic contraction occurs while the regular or repeated contractions usually described as myogenic also become more active. This reaction, except for the preliminary period of inhibition, closely resembles the effect of acetylcholine on the gut in which intestinal excitation succeeds the hypotensive action after about 20 sec. The peristaltic form of response has also been observed with a fall of pressure. Several records of this effect have been taken. DISCUSSION. The method adopted in these experiments is not altogether a satisfactory one for the dissociation of the functions of the great splanchnic nerves, but the results afford certain indications that these functions are more complex than is generally supposed. The method is one that may become more effective with improved technique and should provide a means of obtaining more definite information about these nerves and the characteristics of their excitability. The existence in the splanchnic nerve of hypotensive fibres, vasodilator probably, is easily demonstrated. These are separate from the main group of vaso-constrictors. In one experiment strong Faradic stimulation (coil at 5 cm.) yielded a depressor effect, whereas a weaker current (coil at 8 cm.) led to a pressor effect. The galvanic current applied to the same branch of nerve always elicited a pressor effect. Apart from this instance the depressor fibres were found free from vaso-constrictors and responded to different strengths of current. These depressor fibres do not seem to occupy a large volume of the nerve trunk. No precision could be achieved in determining their orientation, a statement which also applies to the other groups of fibres. Vaso-constrictor effects were much the more common in the excitation of the different artificial

10 FUNCTIONS OF GREAT SPLANCHNIC NERVES. 489 bundles and seemed indeed to indicate that vaso-constrictor fibres were more abundant and more susceptible to ordinary stimuli than the others. With regard to intestinal inhibitory fibres we have to distinguish between a direct primary action and a late effect due to the increased absorption of adrenaline. The initial inhibition was freely obtained on stimulating different bundles and it was frequently followed by an augmentor effect. But this primary inhibition was absent in some clear instances and no form of stimulation of the whole nerve could elicit it. It was not always simply a case of missing the inhibitory fibres going to a particular region of the gut. Sometimes a difference was observed as between right and left nerves, excitation of one causing inhibition while that of the other did not. This may mean a different distribution to the gut. The augmentor action on the gut, already referred to, is distinctly twofold in character, viz. a slow tonic effect and an increase of rapid contractions. A quiescent condition of the intestine is rare after section of both splanchnics. It was well marked in one animal in gestation of about the fifth or sixth week. In this experiment the predominant reaction from both nerves was the slow peristaltic contraction which was accompanied by increase of blood-pressure. The augmentor reaction in general reminded one of vagal effects and set one thinking of such a possibility. None of the authorities on vagal distribution mentions a possible junction of sympathetic and parasympathetic fibres in the splanchnic nerves. McCrea [1924] says that these two sets of fibres join together on their way to the liver. This writer, Mc S win ey and others, whom the latter quotes, also describe such union on the mesenteric and pancreatic arteries. B ayliss and Starling make no reference to such a possibility as splanchnic and vagal union. I have discussed the matter with some prominent anatomists. One of these says that he would not be surprised to learn that a blend of vagal and splanchnic fibres occurred at diaphragmatic level. Atropine in large doses failed to abolish the augmentor reaction in these experiments, but, as B aylis s and Starling point out, atropine does not paralyse the intestinal vagus. Ergotoxine modified the response but did not cause its abolition; further tests with sympathetic paralysants are necessary. Vagal stimulation proper yielded gut reactions very similar to those obtained with splanchnic stimulation, the preliminary inhibition in the latter case being a particular feature in some instances. The action of acetylcholine is of interest; in four or five experiments in which it was

11 490 D. T. BARRY. injected it showed no inhibition, but otherwise closely resembled certain effects of splanchnic excitation. All that can be said at present is that these augmentor fibres which undoubtedly exist in the great splanchnic nerve exhibit a vagal type of reaction, but it is possible that they belong to the sympathetic system. SUMMARY. A method was adopted for investigating the functions of the great splanchnic nerve in the dog and rabbit by splitting the trunk longitudinally into two or three branches and stimulating each separately. Stimulation of a branch sometimes caused a fall of blood-pressure, accompanied by inhibition, augmentation or no change of intestinal movements. Branch stimulation sometimes occasioned marked increased activity of intestinal movements with or without preliminary inhibition. This reaction is similar to that given by stimulation of the vagus nerve, but there is no evidence that the parasympathetic system is in play. The results as stated have been chiefly found in the dog, not satisfactorily in the rabbit. In the former animal the great splanchnic nerve contains hypotensive vascular fibres and augmentor intestinal fibres, which with the generally admitted fibres of opposite function in each case constitute two reciprocal systems. REFERENCES. Alvarez, W. C. (1922). The Mechanism of the Digestive Tract. New York. Barcroft, J., Nisimaru, Y. and Puri, S. R. (1932). J. Phy8iol. 74, 321. Barry, D. T. and Chauchard, A. and B. (1932). C. R. Soc. Biol. Paris, 109, 281. Bayliss, W. M. and Starling, E. H. (1899). J. Physiol. 24, 99. Bercowitz, Z. and Rogers, F. T. (1921). Amer. J. Physiol. 55, 310. Bunch, J. L. (1899). J. Physiol. 24, 72. McCrea, E. D. (1924). J. Anat. 59, 18. McSwiney, B. A. (1931). Physiol. Reviews, 11, 478. Openchowski (1899). Quoted by Page May. Page May, W. (1904). J. Physiol. 31, 260. Spadolini, J. (1917). Arch.fisiol. 15, 229. Weil, A. (1913). Deuts. Arch. Klin. Med. 109, 386. PRINTED IN GREAT BRITAIN BY W. LEWIS, M.A., AT THE UNIVERSITY PRESS, CAMBRIDGE