Cyon thought that the nerve had a cardiac origin, but later investigators,

Transcription

1 Quart. J. Exper. Physiol. (1966) 51, THE ORIGIN OF THE RIGHT AORTIC NERVE IN THE RABBIT. By J: H. GREEN and P. F. HEFFRON. From the Departments of Physiology and Pharmacology, Middlesex Hospital Medical School, London, W.1. (Received for publication 12th April 1966) The right aortic nerve in the rabbit has been traced by dissection under the binocular microscope, and studied electroneurographically. In the middle part of its course it becomes a mixed baroreceptor-autonomic nerve as a result of contributions from the vagus and cervical sympathetic chain. It divides into two branches, a slender one going to the bifurcation of the brachiocephalic trunk, and a larger one passing into the thorax. Electroneurographic studies indicate that the slender branch bears most of the baroreceptor activity found in the aortic nerve, and that the bifurcation of the brachio-cephalic trunk is a baroreceptor area. The larger branch appears to be a cardiac nerve bearing inter alia efferent sympathetic fibres, the activity of which can be reflexly inhibited by increased baroreceptor activity from the area described. IN 1866, Cyon and Ludwig described a nerve in the neck of the rabbit which when the central end was stimulated caused a fall of blood pressure and a slowing of the heart. It was termed the depressor nerve. Ludwig and Cyon thought that the nerve had a cardiac origin, but later investigators, notably Koster and Tschermak [1902] described an aortic origin of it, and it has become known as the aortic depressor baroreceptor nerve, or, more simply, the aortic nerve. In 1924, Tello showed histologically that in the mouse embryo, although the left aortic nerve did indeed arise from the aortic arch, the right one appeared to arise from the bifurcation of the brachio-cephalic trunk: and similar histological observations were reported in 1935 by Nonidez in the embryos of cats, guinea-pigs, and rabbits, and in 1937 by Muratori in adult rabbits. The electroneurographic demonstration that the bifurcation of the brachio-cephalic trunk on the right side is, in fact, a baroreceptor area was made in cats by Stella in 1937, and in dogs in 1948 by Ueda and confirmed by Nakayama [1953]. In 1953 Green, studying common carotid baroreceptor ateas in the cat, named this baroreceptor region Area 1, and Neil [1956] using cats obtained typical baroreceptor reflexes from this area. But doubts still linger concerning the course, origin, and function of the right aortic nerve in the rabbit. In this latter species, unlike the cat and dog, the nerve is separate from the vagus and sympathetic trunk, and on naked eye dissection appears to arise in the thorax. In this investigation we had two objects in mind; to define the origin and course of the right aortic baroreceptor nerve in the rabbit: and to decide by experiment, whether or not the bifurcation of the brachio-cephalic trunk in the rabbit is a baroreceptor area, as it is in the cat and dog. 276

2 Rightaortic nerve Right - vagus nerve Cervical sympathetic chain Right - subclavian artery FIG. 1. Composite diagram of the anatomy of the right aortic nerve in the rabbit, which is easily distinguishable from the vagus and sympathetic trunk. The nerve joins the superior laryngeal nerve and runs with it to join the main vagal trunk. It appears to arise in the thorax but there are branches joining it from the brachio-cephalic trunk and the origin of the right common carotid and right subelavian arteries. - Rt. aortic nerve Cervical sympathetic- -Common carotid art. - Baroreceptor branch Rt. vagus - -Thoracic continuation I 1 1cm FIG. 2. A photograph of a dissection of the lower part of the right side of the neck of a rabbit, showing the right aortic nerve and the small twig from the brachio-cephalic bifurcation. [Toface page 276

3 Rabbit Aortic Nerve 277 METHODS Twenty-five rabbits were studied. They were anaesthetised with intravenous urethane (25% w/v solution). In a few, anaesthesia was induced with ether, and followed by intravenous urethane. The trachea was cannulated. Either the left femoral or the right common carotid artery was cannulated and connected to a pressure transducer, the output of which was displayed on one channel of a multichannel cathode ray oscilloscope. The right aortic nerve was exposed in the neck, and the chest was opened in the midline by splitting the sternum. Electroneurographic recordings were made using saline wick electrodes through A.C.-coupled amplifiers to a second channel of the multi-channel cathode ray oscilloscope. Photographic recording was employed. The upper part of six animals was perfused by a pump via the brachio-cephalic trunk, with oxygenated blood collected from the right atrium. Details of the perfusion system are contained in the paper by Duke, Green, Heffron and Stubbens [1963]. RESULTS The course of the right aortic nerve was traced by dissection using a stereobinocular microscope ( x 6 to x 40 magnification). Fig. 1 is a composite picture constructed from a series of ten rabbits, and it contains the salient features found in most of the animals. The nerve arises near the origin of the superior laryngeal nerve, which is itself a branch of the vagus. It follows a separate course between the vagus and the cervical sympathetic chain. It crosses over the sympathetic trunk, and receives one or more branches from it and from the vagus, so that the nerve which is now travelling down the medial side of this chain is a composite structure consisting of aortic and autonomic elements, and will be referred to as the composite nerve. At a variable point above the subclavian artery, this nerve splits into two unequal parts, the smaller one branching off to the bifurcation of the brachio-cephalic trunk, the larger one continuing into the thorax to terminate in a cardiac plexus deep to the ascending aorta. Thus the apparent course of the right aortic nerve is into the thorax, as indicated by the dotted line, and this represents the traditional view concerning the nerve. The prominence of this apparent thoracic destination can be seen in fig. 2, which is a photograph of a dissection, showing the lower part only of the cervical course of the right aortic nerve, that is, the part after it has crossed the cervical sympathetic chain. The slender nerve to the subclaviancarotid angle appears as a morphologically insignificant branch of the large nerve which continues into the thorax. A very fine twig from this bifurcation to the vagus is not infrequently present in addition to the slender nerve already mentioned. Especially prominent in this specimen are connections between the composite nerve and the vagus and the cervical sympathetic chain. In view of the situation in cats and dogs, one might suspect that the fine nerve, so fine as to be almost invisible to the naked eye, and which

4 278 Green and Heffron arises in the subclavian-carotid angle, is the true origin of the right aortic nerve; that it tracks upwards in the composite nerve, crosses the cervical sympathetic chain, and regains its separate identity in the final part of its course, before joining the vagus or the superior laryngeal nerve. If this is the case, one might further suspect that the apparent continuation into the thorax is in reality a cardiac nerve largely of efferent autonomic nature. CLIPPING THE BRACHIO-CEPHALIC TRUNK. Electro- i,l, 1.. L "I'-F - neurogram -, I - E.c.g. -k - 1 Time marker o0-1 sec. Signal CLIPPING THE RT. COMMON CAROTID ARTERY. 2l...A. lh -1 L. CLIPPING THE BRACHIO-CEPHALIC TRUNK. L-A.-X 1 -A CLIPPING THE RT. SUBCLAVIAN ARTERY. J-i.I11 LḶ.IdII Ito toilli~ll -1LLhLA...iL.A. r"- V " 1-W -T-1- IB I-- -T I -w- -"p -1 -" CLIPPING THE BRACHIO-CEPHALIC TRUNK. I -1- lul LILAIA 1 FIG. 3. The localisation of Area 1 in the rabbit. An electroneurogram of afferent activity in the right aortic nerve (upper trace), electrocardiogram (middle trace), and time marker and signal (lower trace). Strips 1, 3 and 5: clip applied below the bifurcation of the brachio-cephalic trunk at signal marker abolished activity. Strips 2 and 4: clip applied beyond the bifurcation (on right common carotid and subelavian arteries respectively) - activity continues. To investigate these possibilities we used electro-neurographic techniques. Right aortic nerve activity was recorded high in the neck in that part of its course where it is a separate structure lying between the vagus and the cervical sympathetic chain. The source of the baroreceptor impulse activity present in this nerve was localized in three ways. 1. The effects upon few fibre preparations of occluding in turn the arteries proximal and distal to the brachio-cephalic bifurcation were recorded. Fig. 3 shows such an experiment. The brachio-cephalic trunk was clipped in the first, third and fifth strips of record as indicated by the signals, and there was a marked diminution of activity lasting for the duration of the occlusion. In the second and fourth strips, clips were placed on the right

5 Rabbit Aortic Nerve 279 common carotid artery and the right subclavian artery respectively, and in neither case was there very much alteration in nervous activity. Thus the impulses registered in this preparation must have arisen from Femoral B.P. A n-70mm. Hg. Electroneurogrom. T iimme. F-AA 01 sec. ITRACTION OF RIGHT COMMON CAROTID ART. (towards the head) FIG. 4a. The effect of increase in longitudinal tension on brachio-cephalic baroreceptor area. Upper trace; femoral B.P.: middle trace; electroneurogram of a few-fibre preparation from the right aortic afferent activity: lower trace; time. At signal, traction was applied to the right common carotid artery in a headward direction. This caused a marked increase in activity. -- Electro-- neurodgram E.c.g. =- Time - 01 sec. JL J._ I SRACHIO-CEPHALIC TRUNK CLIPPED..TRACTION OF THE SRACHIO-CEPHALIC TRUNK. (Towards the heart) FIG. 4b. Rabbit. The effect of clipping the brachio-cephalic trunk followed by an increase in longitudinal tension upon brachio-cephalic baroreceptor area. Upper trace: electroneurogram of a few-fibre preparation from the right aortic nerve; middle trace: e.c.g.; lower trace: time. At solid signal brachio-cephalic trunk was clipped proximally to brachio-cephalic baroreceptor area, greatly reducing activity. At dotted signals traction was exerted towards the heart, causing a marked increase in activity. an area between the clips, that is, the bifurcation of the brachio-cephalic trunk. 2. Traction upon an artery, tending to pull it away from a baroreceptor area, is known to increase baroreceptor discharge. Fig. 4a shows the effect of traction on the right common carotid artery. Throughout the period of traction there was a considerable increase in activity, which must have originated from the cardiac side of the point of traction. Fig. 4b shows the effect of traction of the brachio-cephalic trunk towards the heart. Fig. 4b (upper strip) is a control. To exert traction on this artery it was necessary

6 280 Green and Heifron to occlude it, hence the low level of activity at the start of fig. 4b (middle strip). Traction was exerted during the periods indicated by the broken lines, and it will be seen that this manoeuvre was accompanied by a considerable increase in impulse traffic. The artery was released at the point indicated by the end of the continuous line (fig. 4b, lower strip) and activity rapidly resumed its control pattern. Thus traction away from the bifurcation, whether exerted from above or from below, produced an increase in activity of the right aortic nerve. 3. The upper part of the animals was perfused by an artificial circulation system via a cannula inserted into the brachio-cephalic artery. The heart Pumnp pressure 2O mm.h 9. electroneurogram. 180 time morker sec. Pump pressure Pump pressure 300 mm.h g..100 mm.hg FIG. 5. Rabbit. Activity in right aortic nerve during perfusion of the upper part of the animal via the brachiocephalic trunk. Upper trace: electroneurogram of right aortic activity; lower trace: time marker. Upper strip: pump produced rhythmic pressure changes at constant mean pressure. Lower strip: pump mean pressure reduced steadily from 270 mm. Hg. to 70 mm. Hg. with constant pulse pressure. was stopped and the pressure in the aortic arch allowed to fall to zero. As can be seen in fig. 5 the nervous discharge was synchronous with the perfusion pump even though aortic arch and other thoracic baroreceptors had been eliminated. Increasing the perfusion pressure (start of the lower strip of record) increased the discharge, but lowering the pressure decreased the pump-synchronous discharge, leaving only a continuous random discharge. In all the animals studied, section of the large thoracic branch of the composite nerve made little difference to the right aortic nerve discharge recorded high in the neck, but destruction of the slender branch to the subclavian-carotid angle abolished virtually all pulse-synchronous activity. In addition, although very little baroreceptor afferent activity was detectable in the larger thoracic branch, it did contain a great deal of sympathetic efferent activity. So we investigated whether a pressure increase in the brachio-cephalic artery would reflexly inhibit this sympathetic activity. In these experiments sympathetic activity was recorded from the thoracic branch of the composite aortic-autonomic nerve. The bifurcation of the brachio-cephalic trunk was isolated by tying off all arteries in communication

7 Rabbit Aortic Nerve 281 with it. A polyethylene cannula connected to a syringe was passed retrogradely along the right subclavian artery into this segment, so that the pressure therein could be raised, without being trasmitted elsewhere in the arterial tree. Thus we were dealing with an isolated arterial segment containing only this baroreceptor area. In fig. 6 the pressure was raised E le ctroneurogra.,.to a E WH.R.w2321ain. Signal seconds. FIG. 6. Rabbit. Reflex changes in sympathetic activity following pressure increase in isolated brachio-cephalic artery. Upper trace: sympathetic activity in thoracic extension of right aortic nerve recorded at slow speed to show respiratory and cardiac rhythms. Lower: rapid injection of saline into isolated brachiocephalic bifurcation at signals. during the signals and there followed a very marked inhibition of sympathetic activity. Lowering the pressure at the end of the signals restored the activity. DiscussioN The reflex effects of stimulating the aortic depressor nerves, namely bradycardia and hypotension, have been known in the rabbit for longer than in any other species. The main origin of the depressor traffic normally present in the nerve on the right side was described first of all in the cat and then in the dog. This paper determines it in the rabbit. It is clear from the experiments just described that by far the greater part of the pulse-synchronous activity in the rabbit's right aortic nerve arises from endings in the region of the bifurcation of the brachio-cephalic trunk. Thus proximal arterial occlusion, which lowered the pressure in the bifurcation and beyond, markedly reduced pulse-synchronous impulse traffic: but occlusion just distal to the bifurcation had little effect upon the nervous activity. Traction upon an artery away from a baroreceptor area increases the firing of the endings in the area [Green, 1954]: and the reflex effects of such traction [Sollman and Brown, 1908, 1912] are such as might be expected from baroreceptor stimulation. Baroreceptors are only pressure sensitive by virtue of the fact that changes in intraluminal pressure alter the degree of distension of the artreial wall. If a plaster cast is fitted round a baroreceptor area, no amount of intraluminal pressure rise will alter the impulse traffic from that area [Hauss, Asteroth and Kreuziger, 1948]. Arterial baroreceptors may be regarded as distortion receptors in the form of a reticulum such that lateral or longitudinal extension causes increased firing. Multi-fibre preparations nearly always exhibit, over and above the prominent pulse-synchronous activity so characteristic of baroreceptors, a VOL. LI, NO

8 282 Green and Heffron considerable background of continuous random activity strongly suggestive of chemoreceptor impulse traffic. In the cat Bianconi and Green [1960] have described functional chemoreceptor tissue in the region of the brachiocephalic bifurcation which they have named the 'right subclavian body'. A similar aggregate of tissue has been demonstrated histologically in the same region in the adult rabbit by Muratori [1937], who further showed that it was innervated by the right aortic nerve. Thus there are reasonable grounds for supposing that some of the random background activity may have arisen from the region of the carotid-subclavian angle. Some may also have arisen from the thorax, for although the large thoracic branch of the composite nerve was almost devoid of afferent pulse-synchronous activity, it did contain a great deal of non-rhythmic impulse traffic. The thoracic branch also contained considerable efferent sympathetic traffic; and as this nerve terminates in a cardiac plexus, we were probably dealing with cardiac sympathetic activity. The reflex effects of stimulating the depressor nerves have been known for a hundred years, and since the advent of electroneurography numerous studies have been conducted on the effects of baroreceptor stimulation upon sympathetic activity in cats [Adrian, Bronk and Phillips, 1932: Bronk, Ferguson and Solandt, 1934: Bronk, Ferguson, Margaria and Solandt, 1936: Gernandt, Liljestrand and Zotterman, 1946: Dowing and Siegal, 1963]. Indeed some of Adrian, Bronk and Phillips' experiments were performed on rabbits also, and we may now extend their observations in this species by noting that increased baroreceptor activity from the bifurcalion of the brachio-cephalic trunk inhibits cardiac sympathetic activity. Further work will be required to determine the reflex effects of stimulation of this baroreceptor area on the various components of the sympathetic nervous system, for Lofving [1961], Downing and Siegal [1963] and Heffron [1965] have produced evidence that the different sympathetic motor neurone pools do not necessarily all behave in the same way. In view of its origin, it might be better if the right aortic nerve were renamed the brachio-cephalic nerve.

9 Rabbit Aortic Nerve 283 REFERENCES ADRIAN, E. D., BRONK, D. W. and PHILLIPS, G. (1932). 'Discharges in mammalian sympathetic nerves', J. Physiol. 74, BRoNx, D. W., FERGUSON, L. K., MARGARIA, R. and SOLANDT, D. Y. (1936). 'The activity of the cardiac sympathetic centres', Amer. J. Physiol. 117, BRONE, D. W., FERGUSON, L. K. and SOLANDT, D. Y. (1934). 'The discharge of sympathetic impulses from the stellate ganglion and its realtion to cardiac reflexes', Amer. J. Physiol. 109, 15. CYON, E. DE and LUDWIG, C. (1866). 'Die Reflexe eines der sensiblen Nerven des Herzens anf die motorischen der Blutgefasse', Ber. s8chi8 Gee (Akad) Wiss 18, DOWNING, S. E. and SIEGEL, J. H. (1963). 'Baroreceptor and chemoreceptor influences on sympathetic discharge to the heart', Amer. J. Physiol. 204 (3), DUKE, HELEN N., GREEN, J. H., HEFFRON, P. F. and STUBBENS, V. W. J. (1963). 'Pulmonary chemoreceptors', Quart. J. exp. Physiol. 48, GERNANDT, B. E., LILJESTRAND, G. and ZOTTERMAN, Y. (1946). 'Efferent impulses in the splanchnic nerve', Acta physiol. scand. 11, GREEN, J. H. (1953). 'Further baroreceptor areas associated with the right common carotid artery in the cat', J. Physiol. 123, p. GREEN, J. H. (1954). Baroreceptor and chemoreceptor control of the circulation. Ph.D. Thesis (Lond.). HAUSS, W. H., KREUZIGER, H. and ASTEROTH, H. (1949). 'Uber die Reizung der Pressorezeptoren im Sinus Caroticus beim Hund', Z. Krei8l.-Forsch. 38, HEFFRON, P. F. (1965). An electroneurographic study of the factors influencing sympathetic activity with special reference to baroreceptors and chemoreceptors. Ph.D. Thes8i (Lond.). KOSTER, G. and TScHERMAK, A. (1902). 'UIeber Ursprung und Endigung des N. depressor und N. Laryngeus superior beim Kaninchen', Arch. Anat. u. Entwick. (suppl.), L6FVING, B. (1961). 'Cardiovascular adjustments induced from the rostral cingulate gyrus with special reference to sympatho-inhibitory mechanisms', Acta physiol. scand. 58, (suppl. 184). MuRATORI, G. (1937). 'Contributi morfologioi allo studio dei recettori aortico-arteriosi dei riflessi cardiopresso regulatori', Arch. ital. Anat. 38, NAKAYAMA-SOSOGU (1953). 'The circulatory and respiratory reflexes from the subclavicular artery and the brachio-cephalic artery', Jap. J. Physiol. 15, NEIL, E. (1956). 'Reflex responses elicited in the cat by perfusion of the root of the right subclavian artery', Arch. int. Pharmnwzodyn. 105, NONIDEZ, J. F. (1935). 'The aortic (depressor) nerve and its associated epithelioid body, the Glomus Aorticum', Amer. J. Anat. 57, NONIDEZ, J. F. (1935). 'The aortic (depressor) nerve and its associated epithelioid body, SoLI.MAN, T. and BROWN, E. D. (1908). 'A depressor reaction obtainable by traction on the carotid artery', Proc. Soc. exp. Biol. N.Y. 5, SOLLMAN, T. and BROWN, E. D. (1912). 'The blood pressure fall produced by traction on the carotid artery', Amer. J. Physiol. 30, STELLA, G. (1936). 'Afferent discharges in the depressor nerve', J. Physiol. 87, 78 p. TELLo, J. F. (1924). 'Developpement et terminaison du nerf d6presseur', Trab. Lab. Invest. biol. Univ. Madr., 22, UEDA, (1948). Quoted by Nakayama.