6I2.89[6I2.563:6I2.79. spinal and of the sympathetic innervation to the tone of the skeletal

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1 6I2.89[6I2.563:6I2.79 6I2.89:6I2.65 THE EFFECTS PRODUCED BY UNILATERAL / LUMBAR SYMPATHECTOMY. I. Cutaneous temperatures and the limb musculature. u / L By G. P. McCULLAGH, G. D. McFADDEN AND T. H. MILROY. 9> (From the Department of Physiology, Queen's University of Belfast.) WITHIN recent years the operations of lumbar ramisectomy or ganglionectomy have been carried out frequently for spastic conditions of the limb and vascular musculatures in man. From the physiological standpoint the possibility of improvement in the former appears to be much less than in the latter. The problem of the relationship of the somatic spinal and of the sympathetic innervation to the tone of the skeletal musculature has been fully discussed by Fulton(l), Forbes(2), Kuntz and Kerper(3), Cobb(4) and many others, and the general conclusion arrived at appears to be that the part played by the sympathetic innervation in the maintenance of skeletal muscle tonus is insignificant, compared to the influence exercised through the reflex somatic spinral pathway. As the controlling influence over the vascular musculature is, on the other hand, essentially a sympathetic or humoral one, such slight disturbances in skeletal muscle tonus as have been described after sympathectomy, might well be produced by metabolic changes resulting from the disturbed vascular control, or from a direct, so-called trophic effect, exercised by the post-ganglionic, non-myelinated fibres on the skeletal muscle fibres. The study of the duration and degree of the cutaneous temperature changes in peripheral parts after interruption of the pre- and post-ganglionic pathways will certainly prove of value when the metabolic changes in the muscles are being subsequently investigated. In the first part of our communication attention will, therefore, be directed to those changes in vascular adjustment, as well as to the general question of the development of the limb musculature in sympathectomized growing animals. As regards vascular adjustments after interruption of the sympathetic pathway, the question arises as to the degree of compensation which can be effected through mechanisms other than the

2 354 G. P. McCULLAGH, G. D. McFADDEN AND T. H. MILROY. one which has been interfered with. Thus, in the operation of lumbar sympathectomy, leaving the sacral ganglia intact, there remains a possible post-ganglionic control, and when this is also withdrawn, there remain the local mechanisms concerned with the inherent smooth muscle tonus, associated with an adrenaline action on the denervated vessel wall. The recovery of cutaneous vascular control is evidently more complete and more rapidly effected after sympathectomy in laboratory animals than in man. Thus Brown and Adson(5) observed a distinct cutaneous temperature rise in peripheral parts, after lumbar sympathectomy, in a case of Raynaud's disease, for 3 years after the operation. The average increase in temperature in the feet, after the operation for this vasospastic condition, amounted to as much as 120, and in a case of spastic paralysis a post-operative increase of In the vaso-spastic condition, prior to the operation, there was a range of temperatures from 150 to 31.20, while after the operation the range under changing conditions was a very limited one, from to In the cat and dog the disturbance in vascular adjustment appears, from general references in the literature, to be a more transient one. In order to investigate possible metabolic changes in sympathectomized skeletal muscle, it was necessary to examine the muscles at different periods after the operation, and also to study the effects produced by exercise, hence a larger number of animals required to be examined than for the study of the vascular changes. The changes produced in cutaneous temperature adjustments were of much the same type in all the animals, so that out of eleven animals operated upon (six puppies and five fully grown dogs) it is only necessary to refer to five. Operation. The left lumbar cord was exposed by the usual retroperitoneal approach. After a morphine-atropine injection and while under chloroform-ether anaesthesia, an oblique lumbo-inguinal incision beginning at the costo-vertebral angle was made, and after severance of the different muscle layers, the transversalis fascia was incised without injury to the peritoneum. The peritoneum with the underlying viscera was gently depressed by warm sterilized gauze. After exposure of the medial psoas border, the muscle was gently retracted and the cord readily exposed from diaphragm to pelvic brim. The cord in the neighbourhood of the uppermost large ganglion was caught by forceps, severed just above this point and then gradually freed by careful section of the rami down to the last lumbar ganglion at the pelvic brim. The cord was cut just beyond this point and removed for histological examination.

3 EFFECTS OF SYMPATHECTOMY. All the animals recovered rapidly and, apart from a mild diarrhcea of about a week's duration or less, appeared to be absolutely normal, so far as the limb musculature was concerned. Cutaneous temperatures were determined by the usual thermoelectric method using copper constantan couples, one in a Dewar flask (containing petrol) kept in a microscope box surrounded by cotton-wool packing, the other fixed to a small vulcanite holder. The latter was applied to the interdigital skin, or to the skin at the base of the main cushion pad of the foot. A description will first be given of the effects produced by this operative procedure on a very young puppy which was kept for 5 months after the sympathectomy. 1. Black spaniel puppy, 4 weeks old, and 1500 g. in weight. Left cord removed on January 18th, 1929, and killed rather more than 5 months later. Before the operation the digital temperatures (with toes held apart) were (Right) and (Left). As the lower part of the cord was being freed, the temperatures were (R.) and (L.). One hour after the operation, when the animal had recovered from the ancesthetic, the temperatures were (R.), (L.). Fig. 1 A gives the temperature graphs for the normal (N.) and /~~~~~~~~~~~~~ \ \~~~~~~~~~~~~~~~~~N Fig. l. A, black puppy. B, black and white puppy. sympathectomized (S.) sides for the first fortnight. During this period the temperature gradually fell on the sympathectomized side. At the outset the difference between the two sides was about 30, towards the end 1 or less. These temperatures were taken after the puppy had been

4 356 G. P. McCULLAGH, G. D. McFADDEN AND T. H. MILROY. resting for some time beforehand. The absence of a vaso-constrictor response to cold on the left side was easily shown by taking the temperatures after the puppy had been playing about on the cold floor of a basement room. For example, on the fifteenth day after the operation, the temperatures before exercise were approximately the same on the two sides (29.70); after a few minutes' exercise the temperature on the right side fell to 27.9, while that on the left side remained unaltered. During the following month exercise of this kind always showed up the difference in adjustment on the two sides, but during the next 3 months this became less evident. The delay in vascular adjustment could readily be shown, however, by warming the feet and legs (dry heat 380) for 5 minutes, and then exposing the warmed parts to the room temperature (12-13 ) for another 5 minutes. The effects produced on the pad temperatures at different periods are shown in Table I. TABLE I. Pad temperature 5 min. Period Pad temperature before after a 5 min. after warming warming period operation A,A (weeks) R. L. R. L * *80 During the fifth month after the operation, the recovery of vasomotor control during the cooling period after warming was almost as good on the left side as on the normal one, but a difference in the cutaneous vascular adjustment on the two sides could readily be shown by placing over the feet cotton-wool, and over this a cooling cap of lead-foil containing carbonic acid snow and ethyl chloride. The vaso-constriction after 1 minute's cooling was evident for at least 10 minutes on the normal side, but passed off within 2 or 3 minutes on the left side. Limb musculature. During the 5 months following the operation, the weight of the puppy increased from 1500 to 9000 g. The muscular development was as good on the operated as on the normal side. X-ray photographs, taken before the operation and 5 months later, showed no differences between the bones and joints of the two sides. Various measurements were taken of the hind limbs before the operation, 2 months and 5 months later, and these may be given to illustrate the development on the two sides. Similar measurements were taken in the case of the other puppies, but, as all showed practically equal growth on

5 EFFECTS OF SYMPATHECTOMY. the two sides, it is only necessary to give the figures for this particular animal (Table II). TABLE II. 23. i iii vi. 29 Circular (in cm.): L. R. L. R. L. R. Thigh Knee-joint Leg S Ankle-joint Foot Longitudinal (in cm.): Femur Tibia Foot Volume (c.c.): No definite qualitative or quantitative differences between the muscle of the two sides could be observed from galvanic stimulation. A current of milliamps. (cathodal closure) was effective when applied over cutaneous motor points (flexor digitorum). The chronaxie values of the gastrocnemii were determined at intervals. Small skin incisions were made over the muscle, so that the silver-silver chloride electrodes might be brought into contact with the muscle. The values (stated in microfarads) varied within the following limits during the last 3 monthsleft gastrocnemius , right gastrocnemius Such slight differences as were frequently observed most probably were due to certain disturbing factors, for example, local variations from cooling. No differences could be observed in the respective knee jerks, nor could any distinct differences in the muscular tone be detected when the limbs were supported with the puppy lying on its back, and the support gently withdrawn. 2. Black and white puppy, 3 months old, and 1720 g. in weight. Left lumbar cord was exposed on June 28th, 1929, and the lumbar ganglia crushed with forceps instead of the normal procedure of removal of the cord. The animal was killed on November 11th, 1929, the weight then being 5030 g. The development of the muscles, bones and joints, and the growth of hair over shaved patches were, in all respects, the same on the two sides. No constant differences could be made out between the muscles of the two sides on testing with the galvanic current, nor were the chronaxie values different. Cutaneous temperatures. Fig. 1 B gives the course of the temperature changes during the fortnight after the operation. As was the case with all the animals operated on during the summer, the temperature differences between the two sides were less marked than in winter.

6 358 G. P. McCULLAGH, G. D. McFADDEN AND T. H. MILROY. 3. Brown puppy, 3 months old, and 5900 g. in weight. Left lumbar cord removed on August 23rd, The digital temperatures for the first fortnight after the operation on the normal (N.) and sympathectomized (S.) sides are given in Fig. 2. The room temperatures during this 35 d E 33 1' ss 3C0 ~ %32 0 j 4 _ _ Days Fig. 2. Brown puppy. period ranged from Subsequent to this period, if the temperatures were taken when the animal had been resting for some time, there was but little difference between the two sides (0.5o-1-0o), but the absence of the reflex vascular adjustments on the operated side could readily be shown during a post-exercise period. From the forty-eighth day after the operation the animal was exercised in a large treadwheel for 10-minute periods four times daily. The stepping rate was per minute and, as the wheel was a heavy one, at the end of each exercise period there were evident signs of fatigue, but no difference could be detected between the condition of the muscles on the two sides. The digital temperatures which follow were obtained (a) before, and (b) and (c) 1 minute and 8 minutes respectively after the exercise. Days after Room operation temperature Right Left (a) (b) (c) (a) (b) (c) (a) (b) (c) For a short period after the exercise the temperatures on the two sides were approximately the same, but in 5 to 10 minutes, especially

7 EFFECTS OF SYMPATHECTOMY. 359 if the room temperature were low, the return of vaso-constriction on the normal side was much more evident than on the operated side. Limb musculature. Four months after the operation the chronaxie values for the gastrocnemii (sciatic nerve stimulation) were determined under amytal anaesthesia, and were found to be 0 02,F (right), 0-03ptF (left). At this time the weight of the animal was 8550 g. and the measurements of the limbs showed no appreciable differences between the two sides. Effects produced by removal of the lower lumbar and upper sacral ganglia. There are only brief references in the literature to the effects produced by interference with the post-ganglionic path. Boshamer(6) compared the effects produced by section of the pre-ganglionic and post-ganglionic paths in the frog. Employing the method of vascular perfusion and determining the outflow, he found that pre-ganglionic interruption on the one side, and post-ganglionic on the other produced the same degree of vaso-dilatation. If the post-ganglionic rami were cut shortly after the pre-ganglionic, no further dilatation was observed, but if a day were allowed to elapse, the vaso-dilatation produced by the pre-ganglionic section having passed off, the subsequent section of the post-ganglionic rami produced a renewed dilatation. Also the recovery from the preganglionic section occurred within a day, while the dilatation after postganglionic section remained for 3 or 4 days. As it is much more important to acquire some information regarding peripheral vascular adjustments after post-ganglionic interruption in the mammal, the operation was carried out in the dog. 4. Large collie. 16 kg. The left sympathetic cord was removed on December 16th, 1929, from just below the fourth lumbar ganglion to a level beyond the third sacral ganglion (limits confirmed by post-mortem). The animal recovered rapidly and, apart from a transient diarrhoea, remained apparently normal. No evidence of any disturbance as regards gait or tendency to muscular fatigue after very strenuous exercise could be observed on the operated side. The digital temperatures of the right and left feet just before the operation were 29 0 and 28.90, and immediately after the operation and 29 7 respectively. It is advisable in this case to give in tabular form the temperatures subsequently observed on the two sides (Table III). The digital temperatures alone are given.

8 360 G. P. McCULLAGH, G. D. MCFADDEN AND T. H. MILROY. TABLE III. Room Days after tempera- Right 'Left operation ture foot foot (Fore paws) (Fore paws) c (Fore paws) (Fore paws) It is evident that the cutaneous vascular disturbances in this dog differ from those observed in the preceding ones. For 3 days after the operation the aveiage temperature difference between the two paws was 4.50, and on the sympathectomized side the temperature remained about the same high level. From the fourth to the fourteenth day the average temperature difference was 9.30, and this was due to the extremely low temperatures on the normal side, as on the operated side the temperatures were also below those observed during the first 3 days. The extremely low temperature on the normal side was not confined to the hind paw, as it was also observed, although to a lesser degree, in the fore paws. Removal of the sacral ganglia on one side certainly interfered with the corresponding part on the other side. Evidently a reflex vaso-constriction of an exaggerated type was produced in peripheral parts. The right thigh and upper fore limb temperatures were not reduced. The marked difference between the upper and lower parts of the limbs could readily be appreciated by running the hand down the limb, the extreme coldness of the feet being very striking. The effects of 10-minute periods of rapid stepping exercise in the treadwheel on the vascular adjustments were frequently studied, and a few examples of the results obtained may be given. The digital temperatures were taken before and 5 minutes after the exercise.

9 EFFECTS OF SYMPATHECTOMY. 361 TABLE IV. Days Before exercise 5 min. after exercise after A A rg Lf operation Right Left Right Left * * The rapid stepping exercise was followed by a rise in temperature on the normal side, while on the operated side the temperatures remained almost unchanged. The variability of cutaneous temperatures on the normal side and its marked absence on the sympathectomized side was evident, even without exercise from the third to the fifth week after the operation. Even when the temperatures on the two sides were approximately the same, the difference in vascular adjustment could be readily demonstrated by the brief application of cooling pads to the feet. For example, on the twenty-second day after the operation when the right and left foot temperatures were and respectively, a brief exposure to cold (cooling lead-foil cap applied to feet for 1 minute) showed the following changes in cutaneous temperatures on the two sides. Minutes after Minutes after cooling Right Left cooling Right Left * The absence of the normal reflex vaso-constriction on the sympathectomized side after cooling could readily be shown in a variety of ways. On the twenty-sixth day after operation, the feet were warmed at 430 (dry heat) for 4 minutes and then exposed to the cold air of the basement room (temp ), and subsequently the dog was kept standing on the cold stone floor of an open corridor. The temperature changes were as follows. Original temperature Right Left After 4 min. at min. later 29*50 30*80 2,, ,, ,, min. on cold floor 1 min. later ,, ,, ,,

10 362 G. P. McCULLAGH, G. D. MCFADDEN AND T. H. MILROY. Limb musculature. Measurements of the limbs 1 month after the operation showed no appreciable difference between the two sides. After half an hour's very active exercise in the treadwheel, the normal and operated sides showed no difference as regards degree of fatigue. On passive flexion of the knee joint, however, there was at all times to be observed on the sympathectomized side a diminution in the resistance offered by the quadriceps femoris, and after the elicitation of the knee jerk there was apparently a more rapid diminution in the tone of the muscle. The chronaxie values for direct stimulation of the gastrocnemii ranged from 004,uF to 008,uF on the right, and from 002,uF to 005,uF on the left side, that is to say, no significant difference. A brief reference may be made to another dog, which showed for many months after the operation a very distinct difference in the cutaneous temperatures after exercise. 5. Dog. 18 kg. Left lumbar cord removed on November 16th, For rather more than a month after the operation the temperature of the left foot was 1-3 higher than that of the right. On the dates mentioned below there was but little difference between the two sides when the animal was resting. The dog was given half an hour's outdoor exercise, and 5 minutes later, after being brought back to the laboratory, the cutaneous temperatures were the following. The effects produced are typical for sympathectomized animals during the winter months. Date Right Left Date Right Left 10. i i * i ii * i E In this animal no differences as regards the hind limb musculature were detectable. SUMMARY. 1. After unilateral sympathectomy in dogs in which the interruption was mainly a pre-ganglionic one, the cutaneous digital temperatures in the resting animal were 10 to 40 higher on the operated side than on the normal one for at least a fortnight after the operation. 2. At later periods, the absence or diminution of cutaneous vascular adjustments on the operated side could be shown in a variety of ways, for example, during a post-exercise period on exposure to cold, or during a cooling period following exposure to heat or by the application of cooling pads to the feet.

11 EFFECTS OF SYMPATHECTOMY After removal of the three upper sacral ganglia in addition to the lower lumbar ones, the usual rise in temperature on the operated side was observed during the first 3 or 4 days. From the fourth to the fourteenth day after the operation there was a much greater difference in temperature than was observed in the other dogs, mainly due to the extreme vaso-constriction on the normal side. Subsequently the difference between the two sides became less marked, but evidence of disturbance in the cutaneous vascular adjustments could readily be shown by the methods previously described. 4. The limb development, osseous, muscular and cutaneous, in puppies was not interfered with by the operation. In one puppy the increase in weight during a 5-month period after the operation was from 1500 to 9000 g. 5. Apart from an appreciable loss in tone of the quadriceps femoris after the post-ganglionic sympathectomy, no definite disturbance in the limb muscles, either in the resting or actively exercised states, could be detected. The chronaxie values of the muscles were not appreciably altered in any one direction by removal of their sympathetic control. REFERENCES. 1. Fulton. Muscular Contraction and the Reflex Control of Movement, p Forbes. Arch. Neurol. and Psych. 22. p Kuntz and Kerper. Amer. J. Physiol. 76. p Cobb. Physiol. Rev. 5. p Brown and Adson. Arch. Neurol. and Psych. 22. p Boshamer. Pfluegers Arch p PH. LXIX. 24