however, confined their attention to isolated nerves, and their methods have

Transcription

1 72 J. Physiol. (I943) I02, I6.3 THE EFFECTS OF PRESSURE ON CONDUCTION IN PERIPHERAL NERVE BY F. H. BENTLEY AND W. SCHLAPP, From the De.partments of Surgery and of Physiology, Manchester University (Received 14 December 1942) Though relatively slight pressure on a nerve can stop conduction, it only does so when applied locally. Normal nervous activity is possible under conditions of generally increased pressure such as exist on the sea bed, and it has been shown experimentally [Ebbecke & Schaefer, 1935; Grundfest & Cattell, 1935] that if a nerve be totally enclosed in a pressure chamber conduction only begins to fall at pressures between 6000 and 8000 lb./sq. in. A review of the literature reveals numerous reports of experiments designed to demonstrate the effects of pressure applied locally. Many investigators have, however, confined their attention to isolated nerves, and their methods have been so various that results are not strictly comparable. The beautifully simple experiments of Weir Mitchell [1872] showed that a pressure of a column of mercury in. high interrupted conduction in the sciatic nerve of the rabbit in sec. The principle of applying fluid pressure was further developed by Meek & Leaper [1911] and later by Gasser & Erlanger [1929], who used electrical methods for recording nervous activity and were able to show that a pressure of 25 lb./sq. in. blocked conduction in frog's sciatic nerve in a few minutes and that the larger fibres were affected first. It is clear that in nerves with intact circulation the effects of pressure might be due to deformation or to ischaemia or to both. The experiments of Gasser & Erlanger [1929] suggest the former explanation; and there is direct evidence that the deformation caused by local pressure is most severe at the boundaries of the compressed part [Edwards & Cattell, 1928]. On the other hand, the experiments of Lewis, Pickering & Rothschild [1931] on man and those of Clark, Hughes & Gasser [1935] on animals showed that with quite low pressures a nerve in a limb may be blocked in from 16 to 40 min., and that ischaemia was the mechanism involved. These experiments have been confirmed by us [Bentley & Schlapp, 1943]. In man it is not uncommon to find that localized pressure of some hours' duration over a nerve trunk results in a temporary paralysis. Whether such a

2 PRESSURE ON NERVE3 73 block is due to ischaemia or to the direct effects of pressure is not clear, and it is the purpose of the experiments described in this paper to inquire further into the relation between pressure and ischaemia in producing a block to conduction. METHODS The experimental procedures as regards the preparation, stimulation and recording of nervous activity have already been described [Bentley & Schlapp, 1943]; there remains the method used to apply pressure directly to nerves. T cm. Fig. 1. Sectional view of apparatus for compressing nerves. AA, brass chambers hinged at B and covered with rubber membranes between which the nerve N is placed. C is an adjusting screw and D a stop to prevent too close approximation. The chambers are supplied with air at the required pressure through the tubes T. In principle it consists in placing the nerve trunk between pneumatic cushions at a fixed distance apart. These are inflated to the required pressure by means of an air pump. The constructional details of the apparatus are shown in Fig. 1.

3 74 F. H. BENTLEY AND W. SCHLAPP A calibration was obviously desirable in order that the actual pressure applied to the nerve might be known. The apparatus (A, Fig. 2) was therefore applied to an excised piece of the external jugular vein of a cat. The ends of the vein were tied to small glass tubes leading to a manometer (B) on the one hand and a tap (C) on the other. The vein and the tubes were filled with Ringer's solution and the pneumatic cushions (A) distended to a known pressure of up to 150 mm. Hg. The manometer (B) was filled with mercury so that a rather lower pressure was developed in that part of the vein connected to it. With the tap (C) open the pressure in the pneumatic cushions was now slowly released and the mercury meniscus (D) observed for movement, which would show cm 1 cm2 s. Fig. 2. that fluid was passing through the vein. This invariably happened when the cushion and manometer pressures were within 5 mm. of each other. It may therefore be assumed for practical purposes that the pressure in the cushions is transmitted directly to the nerve. The apparatus was used in two forms, 2 and 4 cm. long respectively, but they gave identical results. In applying the apparatus the necessary length of nerve was freed in the lower third of the thigh, slightly raised on glass hooks, the cushions adjusted on either side and distended so that the nerve was held between them. The glass hooks were removed, the skin sutured above and below the apparatus, and a gauze swab soaked in saline placed over it. The external popliteal nerve was stimulated in the upper part of the thigh and records were made from the nerve at the ankle. The effects of pressure on conduction were studied in the 'A' fibres only [Gasser, 1937].

4 PRESSURE ON NERVE RESULTS Preliminary experiments showed that with applied pressures of mm. Hg the size of the action potential remained constant for at least 6 hr. With pressures between 130 and 200 mm. Hg however, it became reduced in 40 min., indicating that conduction had ceased in a number of fibres. The block continued to develop and was complete or almost so in 2-3 hr. As the action potential became reduced the first part of the 'A' wave declined more rapidly than the last, showing that conduction failed first in the fibres with the fastest conduction rate, or in other words those of larger diameter [Gasser, 1937], though a complete separation of fast and slow fibres was not seen. The part of the nerve below the pneumatic cushions was unaffected, as a normal response was obtained throughout the experiment when stimulation was below the block. In these experiments the pressure applied was made approximately equal to the carotid blood pressure, as the block was at first interpreted in terms of anoxia consequent on ischaemia. Nevertheless, an attempt to restore conduction during the period of decline by the intravenous injection of 1 mg. of adrenaline hydrochloride or of 10 units of posterior pituitary extract failed, though the procedures markedly increased the blood pressure. Conversely, attempts to hasten the onset of block by repetitive maximal stimulation for periods of 6 min. at 65 per sec. and 33 mmn. at 170 per sec. were unsuccessful. The action potential was indeed somewhat reduced during stimulation, but recovered fully within half a minute of its cessation. The results of twenty-seven experiments with various pressures are reproduced diagrammatically in Fig. 3; they have been arranged so that the applied pressures-represented for each experiment by a black column-form an ascending series from 10 to 200 mm. Hg. The associated white column gives the magnitude of the carotid blood pressure in each case. The results fall into three groups. In the first (A) the action potential was affected only very slightly or not at all after 21-3 hr. The pressure applied was up to 100 mm. Hg, a pressure less than that of the blood in the carotid artery. In the second group (B) there was partial. disappearance of the action potential in 3 hr., indicating partial block. The applied pressure in this group was 120 mm. Hg, somewhat greater than that in the carotid. In the experiments of the third group (C) the nerve was found to be completely blocked or almost so in 24-3 hr., and the applied pressure was between 130 and 200 mm. Hg. In all but two of the experiments of this group the blood pressure was less than the applied, and if these results were for the moment neglected it could be said that nerve block occurs only when the applied pressure exceeds that in the carotid artery. These two experiments, however, show that a nerve may be blocked by the application of a pressure less than that prevailing in the carotid artery. The results

5 76 F. H. BENTLEY AND W. SCHLAPP taken as a whole suggest that there is a critical value of about 130 mm. Hg for the production of nerve block by pressure within the time limits used. When the pressure is released the subsequent behaviour of the compressed part differs in the three groups. In the first (A), in which conduction had been affected only slightly or not at all, no further change occurred in the next 2 hr. In the second group (B), where there had been partial block, one nerve recovered and the other progressed to complete block in 2 hr. In the third group (C), in which block was complete or almost so, there was no recovery after 2 or 200 A B C Fig hr. Indeed, the reverse of recovery was sometimes observed. In five experiments the small potential remaining when the pressure was released disappeared in the course of half an hour just as though the pressure had been continued. In one case where the observation was continued for 131 hr. after the establishment of complete block the action potential recovered to about 30% of its original height. In eight experiments in which block was complete or almost so, the nerve was explored after removal of the pneumatic cushions by moving the recording electrodes centrally while stimulating at the top of the thigh as usual. The following results were obtained: Situation In mid-leg One cm. below lower edge of compressed part A few mm. above lower edge of compressed part In middle of compressed part A few mm. below upper edge of compressed part One cm. above compressed part Action potential Absent or minute Small-200V. (normally 2-mV.) Slightly larger-30o,v. Considerable increase-1.5 mv. Larger-2 mv. Still larger-3 mv. These results have been expressed diagrammatically in Fig. 4.

6 PRESSURE ON NERVE There was thus a sudden increase in the action potential in the lower part of the compressed length, a further increase as it was traversed, and another considerable one just above it. As it was thought that this result might be dependent on some local anatomical feature, an experiment was performed in which pressure was applied to the nerve in the middle of the leg. An identical result was obtained. The block is thus mainly situated at the extremities of the compressed part, and it is here that Calugareanu [1901] and Edwards & Cattell [1928] showed that deformation and displacement of nerve substance were most severe. Various changes were visible to the naked eye in the nerve when the pressure was released. The surface of the compressed part was moist, and if there was a film of blood over it this was bright red in colour. The nerve substance Compressed ~~~potion cm. Fig. 4. of the compressed length was rather pale and somewhat flattened; and the blood vessels on its surface were sometimes not obvious at all, sometimes pale red, and sometimes of a brownish hue. The vessels on the remainder of the nerve, though occasionally congested, showed no other abnormality. It was not possible to relate the appearance of the superficial blood vessels to the state of conduction in the nerve. Immediately after removal of the pneumatic cushions in experiments in which conduction had been abolished, the superficial blood vessels of the compressed part were seen to fill slowly from above and below. This reflux did not give the impression of an active circulation. In order to inquire further into the circulatory state a solution of Evans blue was injected intravenously. This dye remains in the plasma and does not normally leave the circulation for many hours. In the concentration used 120 mg./kg.) its presence was obvious from the deep blue colour which appeared in the superficial vessels of the external popliteal nerve within 10 sec. of the injection. Obviously the blue colour can only develop in vessels in which blood is circulating.

7 78 F. H. BENTLEY AND W. SCHLAPP In experiments in which, following the release of pressure, conduction was maintained completely (group A) or in part (one experiment of group B), injection of the dye showed that there was an active circulation in the previously compressed part, as the epineural vessels became deep blue in colour within a few seconds. There was often some blue staining of the nerve substar4ce itself, and it is thought that this appearance of the dye outside the blood vessels indicates that they have been damaged in the regions where staining occurred. In experiments in which the nerve was still blocked 2 or 3 hr. after the pressure had been released (one experiment group B, and all experiments group C) the injected dye showed in the longitudinal vessels of the nerve up to both edges of the compressed part, but the vessels of the latter remained red. The difference was a very striking one, and the sharp line of demarcation corresponded accurately to the limits where pressure had been applied. It was concluded that the early filling of the vessels after the release of the pressure was in fact a passive reflux and that there had been no active circulatory return. In view of what has been said regarding the situation of the block, it was interesting to observe that there was considerable blue staining of the nerve substance above and, to a greater extent still, below the compressed part. The staining extended for about 1 cm. on either side of it and also for a few mm. into it. It might be assumed from these experiments that the failure of conduction in the compressed part is due to local ischaemia. Yet an applied pressure of mm. Hg should have been sufficient to stop the circulation in the small vessels of the nerve trunk where the blood pressure might well be of the order of one-half of that in the carotid. Indeed, it was possible to show experimentally that local ischaemia was not responsible for the development of nerve block. In two experiments pressures of 60 and of 65 mm. Hg respectively were applied to the nerve for 2 hr. No failure of conduction was observed. Fifteen minutes before the pressure was released Evans blue was injected intravenously. Within a few seconds the dye was visible in the superficial blood vessels of the nerve up to the edge of the pneumatic cushions. Just before the pressure was released ligatures were tightly tied round the nerve trunk above and below in order to stop the circulation, and the pneumatic cushions removed. When the,compressed part was examined immediately afterwards there were sharp lines of demarcation between the red vessels of the compressed part and the blue -ones above and below it. Thus in spite of the stoppage of the circulation, conduction through the compressed part had persisted. It has been shown elsewhere [Bentley & Schlapp, 1943] that conduction ceases in about 30 min. in the nerve of a limb rendered anoxic by the application of a tourniquet. It was shown above that a pressure of 60 mm. Hg applied to a nerve trunk may produce ischaemia in portions 2 or 4 cm. long and yet con-

8 PRESSURE ON NERVE 79 duction is uninterrupted in 21 hr. The compressed part could not therefore have been anoxic. There seem to be only two ways in which it could have effected gaseous exchange-through the rubber membranes of the pneumatic cushions or by diffusion from the normally vascularized nerve above and below it. The first explanation is to a high degree unlikely, and it was excluded by distending the pneumatic cushions to a pressure of 185 mm. Hg with nitrogen containing 5% of carbon dioxide. The nerve was not blocked until 2 hr. 40 min. had elapsed. This time is the same as that found when the apparatus was.c To amplifier I I Fig. 5. distended with air, and does not indicate that diffusion of oxygen or of carbon dioxide through the rubber membranes of the pneumatic cushions plays any part in maintaining activity in the compressed nerve. The other explanation was much more acceptable, especially when the wellknown experiments of Kato [1924] regarding the diffusion of anaesthetic vapours along isolated nerves are borne in mind. The diffusion of oxygen along anoxic nerves was investigated as follows (Fig. 5). A tourniquet (A) was applied at the root of the limb, the external popliteal nerve cut at the ankle (B), freed up to the level of the knee (C) and threaded through a rubber tube 4-5 cm. long (D) and which was provided with side tubes (E, F). The ends of the tube D were plugged with vaseline and the

9 H. BENTLEY AND W. SCHLAPP skin sutured over the nerve and tube. The side tubes, which were allowed to protrude from the limb, were used to pass a stream of oxygen along the nerve, the inflow and outflow being checked by bubbling it through water. One hour after the application of the tourniquet and 50 min. after the oxygen supply was begun, the nerve was stimulated at the level of the knee 2 cm. above the tube (C). The action potential at the ankle 5 cm. below the tube was 80-85% of that which had been recorded immediately after the application of the tourniquet. It will be recalled that in a limb with a tourniquet in which the external popliteal nerve has been freed from its bed and replaced, conduction ceases in about 50 min. [Bentley & Schlapp, 1943]. The experiment described above shows that oxygen diffuses along the nerve in such a way as to maintain almost full activity over a length of 5 cm. It receives confirmation from a repetition using air instead of oxygen. As might be expected, the influence did not extend so far. The section potential was 75% of the normal size 2 cm. below the air tube and fell to 25% in the adjacent 2 cm. DISCUSSION It is clear that pressure may be applied locally to a nerve in such a way as to render it ischaemic without impairing conduction. Our experiments lead us to the conclusion that with applied pressures between 60 and 100 mm. Hg the maintenance of conduction in an ischaemic compressed portion of nerve, up to 4 cm. long, is due to the diffusion of oxygen from the neighbouring vascularized parts of the nerve. The observation that rapid stimulation of the nerve for j hr. did not accelerate the onset of block supports the view that the nerve had a means of replenishing its oxygen. When pressures between 100 and 200 mm. Hg are applied, however, partial or complete failure of conduction results. It is conceivable that oxygen diffusion ceases when the applied pressure exceeds 100 mm. Hg, thus rendering the nerve truly anoxic; on the other hand, the pressure may act directly on the nerve. The first explanation seems unlikely on theoretical grounds, and there is evidence in support of the second view: (1) The situation of the block at the extremities of the compressed part where deformation and displacement are known to be most severe is very suggestive of mechanical injury. We believe that the failure of the circulation to return when the pressure is released is due to concomitant injury of the blood vessels which is made evident by the considerable extravasations of dye which occur in these situations. (2) The time taken for the establishment of nerve block by direct pressure is much longer than that observed in ischaemia. (3) Recovery did not occur within 3 hr. of the release of a pressure which had produced complete block, and where the block had been incomplete it usually

10 1P.LD,.BS8URB ON NERVE 81 became complete subsequently. This is the reverse of what happens after ischaemia, where we have shown [Bentley & Schlapp, 1943] that recovery may occur when the nerve has been in an ischaemic condition for up to 4 hr. It is evident from these experiments and from those on ischaemia that pressure applied to a nerve can produce block to conduction in two different ways: (1) If a pressure of 130 mm. Hg or more is applied directly to a portion of probably deformation of nerve 2 or 4 cm. in length, the mechanical effects nerve substance at the boundaries of the compressed part-will produce a block to conduction. The block only becomes apparent in 40 min. and does not become complete for 2 or 3 hr. When the pressure is released there is no recovery during the next few hours-indeed, the block, if incomplete, may become more severe. (2) If the pressure is applied through the full thickness of the limb by means of a pneumatic cuff, conduction ceases in about 30 min. as a result of anoxia of the nerve, and recovery after release of the pressure occurs when the circulation is restored even though a pressure of 250 mm. Hg has been maintained inside the cuff for 3 hr. The difference between the effects of direct and indirect pressure is probably associated with differences in magnitude and distribution of pressure under a 4 cm. pneumatic cuff as compared with pressure directly applied to the nerve. It is not known whether the block that results from the application of direct pressure would recover in a few days, i.e. a transitory block, or would proceed to Wallerian degeneration. The partial recovery which occurred in 133 hr. is suggestive of the former view. SUMMARY 1. A method of applying pressure directly to nerves in the anaesthetized animal is described. 2. It is shown that pressures up to 100 mm. Hg do not produce block in 21-3 hr. At a pressure of 120 mm. of mercury there is some interference with conduction, while with pressures between 130 and 200 mm. Hg a block is first apparent in about 40 min. and is complete or almost so in 21-3 hr. 3. Repeated stimulation of the nerve does not accelerate the onset of block, and raising the blood pressure by injection of adrenaline or of posterior pituitary extract does not retard it. 4. Recovery does not occur.within 3 hr. of the release of a pressure which has produced complete block, but in one experiment observed for 13j hr. conduction recovered in about one-third of the fibres. Where the block is incomplete recovery may occur or it may become complete subsequently. 5. There is a critical value of about 130 mm. Hg for the production of nerve block if the pressure is applied for a period of 2-3 hr. This pressure is not related to the carotid blood pressure. PT. oii. 6

11 82 F. H. BENTLEY AND W. SCHLAPP 6. Pressure block has different characteristics from block due to ischaemia. Thus the time taken for the establishment of nerve block by direct pressure is much longer than that observed in ischaemia; and the absence of recovery within a few hours of the release of pressure is the reverse of what happens after the relief of ischaemia. 7. A pressure of 60 mm. Hg will render a 4 cm. length of nerve ischaemic, but does not affect conduction. Although the compressed part is ischaemic it obtains oxygen by diffusion from the adjacent vascularized nerve. 8. The block produced by pressure is mainly situated at the extremities of the compressed part, where deformation is most severe. 9. The deformation is associated with injury to the nerve vessels, and absence of recovery after release of pressure is accompanied by failure of return of the circulation in the vessels of the compressed part. The circulatory failure, however, is not an important factor in the production of pressure block. The expenses incurred in this work were in part defrayed by grants to one of us (F. H. B.) from the Medical Research Council and from the Dickinson Trust of Manchester University. REFERENCES Bentley, F. H. & Schlapp, W. [1943]. J. Phy8iol. 102, 62. Calugareanu, D. [1901]. J. Physiol. Path. gin. 3, 413. Clark, D., Hughes, J. & Gasser, H. S. [1935]. Amer. J. Physiol. 114, 69. Ebbecke, U. & Schaefer, H. [1935]. Pflug. Arch. ges. Physiol. 236, 678. Edwards, D. S. & Cattell, McK. [1928]. Amer. J. Physiol. 87, 359. Gasser, H. S. In Gasser, H. S. & Erlanger, J. [1937]. Electrical Signs of Nervous Activity. Philadelphia. Gaasser, H. S. & Erlanger, J. [1929]. Amer. J. Physiol. 88, 581. Grundfest, H. & Cattell, McK. [1935]. Amer. J. Physiol. 113, 56. Kato, G. [1924]. The Theory of Decrementless Conduction in Narcotised Region of Nerve. Tokyo. Lewis, T., Pickering, G. W. & Rothschild, P. [1931]. Heart, 16, 1. Meek, W. J. & Leaper, W. E. [1911]. Amer. J. Physiol. 27, 308. Weir Mitchell [1872]. Injuries of Nerves and their Consequences. Philadelphia.