Principles of General Physiology

The second method is one in which the blood flow from the vein of an organ is estimated. If it comes in drops, these may be intercepted by falling on° to a lever which actuates a signal, electric or pneumatic. If more copious, it may be measured in a "tipper," such as that described by Condon (1913), or iii a siphon outflow recorder, such as that of Ishikawa and Starling (1912) or of Gunn (1913). Details of various methods will be found in Frank's article (1913).

Vasomotor Nerves.— The supply of the smooth muscle of the arterioles by both excitatory and inhibitory nerves has been referred to above (page 403) in the general discussion of excitation and inhibition. The name "vasomotor" should be applied to both classes, since both bring about movement of the vessel wall. Confusion is sometimes caused by using " vasomotor " as equivalent to " vaso-constrictor." The first clear proof of the existence of vaso-constrictor nerves was afforded, independently, by Brown-Sequard (1852) and by Claude Bernard (1852). They found that the blood vessels in the region supplied by the cervical sympathetic nerve were constricted when the peripheral end of the nerve was excited.

Fig. 235 is a copy of a picture by Lhermitte in the Luxembourg Gallery in Paris .laude Bernard is shown demonstrating to friends and pupils this effect on the ear of the rabbit ; at least, this appears to be the nature of the experiment At a later date (1858) Bernard proved the existence of vaso-dilator nerves by stimulating the chorda tympani nerve, and observing the greatly increased outflow from the vein of the submaxillary gland. The reader may, perhaps, find 1 ig. 236 ot interest in connection with the great physiologist

Most of the organs of the body have been shown to have a supply of both vasoconstrictor and vaso-dilator nerves. Fig produced in the tongue of the dog by&th produced by the cervical sympathetic nerve. FigT 109 figure by Retzius of the nerve plexus around arterioles Although nearly all the organs of the body are thus supplied with vasomotor nerves, it is remarkable that no experimental evidence of a satisfactory nature has been brought to show their presence in the brain (see Bayliss and Hill ™95) ; appears that the central nervous system is of such importance that when more blood is required by it, this blood has to be provided by rise of pressure, produced by vaso-constriction in the rest of the organism.

The coronary arteries of the heart are probably in a similar position. But here there appears to be no need for constrictors, since the heart is always at work, and increased supply is automatically provided by rise of aortic pressure and by the great sensibility of the coronary vessels to the metabolites produced by the heart in contraction. For some time the supply of vaso-constrictors to the lungs was in doubt. Bradford and Dean described their presence, Brodie and Dixon denied it. Fiihner and Starling (1913) finally proved it by the action of adrenaline.

Space does not permit of details of the anatomical origin of the various supplies to individual organs. These will be found in my article (1906, 3), and in the papers quoted there. The vaso constrictors are all contained in the sympathetic outflow, as described by Gaskell. The vaso-dilators have a more varied origin, especially from cranial and sacral automatic systems. Whether the sympathetic proper contains any vasodilator fibres is somewhat doubtful. Reference has been made (page 428) to the possibility of reversal of constriction under the action of drug?, etc.

The remarkable nature of the vaso-dilator supply to the limbs, skin of the trunk, and, probably, of the ears and face, and of the intestine requires mention. Strieker had described vascular dilatation in the foot of a dog when he stimulated the peripheral ends of dorsal roots in the sacral region, but the statement was not generally accepted until my work (1901, 2), on account of the apparent contradiction of the law of Bell and Magendie (Fig. 237). I showed that the fibres concerned have anatomical relationships similar to those of the ordinary sensory fibres, and

appear to be identical with them. I suggested that there might be a peripheral nerve network around the arterioles, common to both sensory fibres and vaso-dilator nerves. This view was confirmed by the work of Ninian Bruce (1910). Starting from the fact that paralysis of sensory nerves by cocaine prevents the application of oil of mustard from causing inflammation, he showed that the inflammation produced by this irritant is due to an axone reflex to the arterioles. It is unaffected by mere section of the nerve trunk, but disappears if the nerve fibres are allowed to degenerate. Thus a sensory fibre has a vasodilator branch to an arteriole, and, when the receptor organ is stimulated, the nerve impulse, as it reaches the branch, passes along it and causes dilatation of the arteriole (see the diagram of Fig. 145, page 474). It will be noted how the four classical characteristics of inflammation — heat, pain, redness, and swelling — fit in with this view : pain from the sensory component, heat, redness, and swelling from the vascular dilatation. I found also (1902, 3) that stimulation of

OF THE FIRST SACRAL DORSAL ROOT. — Nine da vs after removal of the spinal cord from the second lumbar segment downwards, leaving intact the dorsal root ganglia. The ventral roots were completely degenerated and inexcitable. the dorsal roots of the splanchnic area caused dilatation in the intestine, so that Upper curves in each fig., volume of intestine of cat, recorded by plethysmograph. Fall indicates arterial constriction. Lower curves, arterial pressure in aorta. Mercury manometer. The initial normal height was 90 mm.

mercury. Each division of the scale represents 2 mm. of mercury change of pressure. Upper signal, time in ten-second intervals. Lower signal, stimulation. 1, Stimulations, three in number, of the central end of the median nerve. Rise of blood pressure, caused by peripheral constriction, as shown by the volume of the intestine. 2, Stimulation of the central end of the vagus (depressor). Fall of blood pressure, caused by peripheral 3, Similar to previous curve. Showing effect of more prolonged stimulation in producing permanent fall of

blood pressure, probably owing to secondary effect of anaemia on the heart. the dilator fibres contained in the splanchnic nerves may not be of sympathetic oricrin. The relation of these anlidromic impulses, as I called them on Lingley's suggestion, to herpes has been indicated above (page 290). Affections of the Gasserian ganglion may also be mentioned. It is found in some cases that a nerve, which ordinarily causes vaso-constriction, may, after certain drugs such as ergotoxine (see the paper by Dale, 1906), produce dilatation in the same region. The obvious explanation is that usually given, namely, that the nerve contains both kinds of fibres, and that the constrictors are paralysed by the drug. Some effects of this kind have been discussed above,

Lower curve, arterial pressure. Zero. 20 nun. below time signal. The vaso-dilator supply was cut oft by previous section of the spinal cord in the middle of the lumbar region ; that is, on the cranial side of the outflow of these nerves. The central end of the median nerve (pressor) was stimulated at the time indicated by the upper signal. t"p)>er curve, arterial pressure. Zero, 30 mm. below time signal. Yaso»constrictor supply cut off by section of the sympathetic nerve in the neck.

A rise of blood prt-ssunoccurs when the central end of the median nerve is stimulated. This is accompanied by diminution in volume of the ear, although the only vasomotor nerves left were dilators. and it was pointed out that the possibility of the effect of the constrictor fibres being reversed by the drug has not yet been definitely excluded. Vasomotor Reflexes, — General peripheral constriction or dilatation can be produced reflexly, with rise or fall of arterial pressure. While nearly all sensory nerves produce a rise of arterial pressure, there is a particular nerve, the depressor, which always normally causes a fall.

The depressor nerves were discovered by Cyon and Ludwig (1866), who found that, in the rabbit, there is a branch of the vagus which proceeds to the heart and consists of afferent fibres from this organ. When the central end of this nerve is stimulated, with the main trunk of the vagus intact, a slowing of the heart beat is caused, accompanied by a fall of blood pressure. That the fall of blood pressure is not entirely due to the cardiac inhibition, was shown by the fact that it was still present when the vagus nerves were cut, and no change in the heart beat occurred. Fig. 127 (page 423) is a typical form of depressor curve in the rabbit with vagi cut. The fall of blood pressure is, in fact, produced by general vaso-dilatation in all organs of the body which are supplied by vasomotor nerves. Fig. 238 shows that it occurs in the intestine, and Fig. 120 (page 412) that it occurs in the leg.

The peripheral receptor ends of the depressor nerve are situated not only in the heart but in the arch of the aorta, and its function appears to be to protect Arterial pressure in cat, upper curve. Zero, 33 mm. below time signal. Upper signal line, drops of blood from vein of submaxillary gland. Cervical sympathetic cut, so that the gland was supplied with vaso-dilator fibres in the chorda tympani nerve, and these were the only vasomotor nerves present. The first part of the fall of pressure is accompanied by vascular dilatation in the gland,

shown by the more rapid succession of drops. The later continued fall, after ceasing the stimulation, is, no doubt, due to failure of the heart from insufficient the heart from too great a rise of blood pressure. We see in Fig. 106 (page 386) how it is excited at each heart beat, but it has been found difficult to show experimentally that a rise of aortic pressure, produced otherwise than by each heart beat, stimulates it. In most mammals the depressor fibres are contained in the trunk of the vagus, and it is not always possible to obtain their effect apart from the opposite pressor effect of the ordinary sensory fibres in the vagus trunk. In the cat the vagus acts as a depressor nerve only.

Fig. 238 gives instances of a reflex rise and a reflex fall of arterial pressure, and the plethysmograph curve of the intestine shows that the rise is produced by a peripheral vaso-constriction and the fall by dilatation. Now we have seen that there are both constrictor and dilator fibres leaving the central nervous system, so that there must be centres from which they arise. It has long been known that there is a particular part of the bulb which ;u-ts as centre for the former, although it is probable that wluit is called the " vasonmt or centre " is rather a nerve tract containing fibres from scattered centres. The vaso-dilator centre has not yet been localised.

It is evident, then, that reflex vaso-constriction or dilatation might each be Fu;. 242. Similar experiment to that of Fig. 241, hut on the rabbit, the central end of the depressor nerve itself being stimulated. There is very little fall of blood pressure, owing to the use of a mercury compensating arrangement. produced in two ways ; the former, either by excitation of the constrictor centre or by inhibition of tone in the dilator centre, supposing such tone to be present ;

VASCTLAK DILATATION i\ THK HIND LIMP. HV KXI ITATION OK DILATORS. — Abdominal sympathetic cut. Coincident with the fall in arterial pressure, due to the depre-^n- film-* in the vajrus, there is dilatation of the limh, althoujrh there were no vaso-constrictors whose the latter, by excitation of the dilator centre, or by inhibition of tone of the constrictor centre, supposing it to be in a state of tonic excitation. In early work on vascular reflexes, the existence of vaso-dilator nerves was not taken account of, so that^the peripheral dilatation produced from the depressor nerve was ascribed by Cyon and Ludwig to inhibition of the constrictor centre.

In 1893, in the course of investigations with this nerve, I found that the phenomena were not to be satisfactorily explained on this view alone, and suggested (p. 317) that, both in pressor and in depressor reflexes, inhibition of the one centre is associated with excitation of the opposite one. Ostroiimov, working with Heidenhain (1876), had already expressed the view FIG. 244. Experiment similar to that of the preceding figure. The reflex dilatation obtained after section of the vaso-constrictors in the abdominal sympathetic can be abolished by subsequent section of the spinal cord at the second lumbar nerve, by which operation the connection of the vaso-dilators with the centre is severed.

inhibiting its natural tonus. C, Vaso-constrictor fibre also ending in A, but exciting it. These two kinds of fibres arise from the dilator respectively. F, Afferent depressor fibre, dividing into two (+) excites the dilator centre. R, Pressor fibre of ordinary sensory nerve, causing inhibiting D.C. a, b, c, d, The respective synapses of these branches with the efferent neurones. The probable intermediate neurones are, for the that the reflex dilatation in the skin vessels produced by the depressor nerve is due to excitation of vaso-dilator fibres, but it does not seem to have occurred to these and subsequent investigators that both excitatory and inhibitory actions are concerned. After Sherrington's work on the reciprocal innervation of skeletal muscle, I took up the question again (1908, 2), and showed that this mode of innervation applies also to vasomotor reflexes, although, of course, the phenomena are complicated by the fact that both the centres and the effectors can be excited or inhibited. There are thus four cases to be considered, which must be done

At the signal, the central end of the dorsalis pedis nerve of the same leg was stimulated, causing a slight fall of blood pressure, with marked dilatation of the leg. Note that the usual effect of a sensory nerve is to cause reflex vaso-constriction in the body generally. At the signal, the central end of the anterior crural nerve of the same leg was stimulated. A rise of blood pressure is seen, accompanied by dilatation of the leg. Fig. 239 shows that stimulation of a sensory nerve from another region, "namely, the median of the arm, causes vaso-constriction in the leg. This fact is also shown in

C, Upper curve, volume of hind limb of dog. Lower curve, blood pressure. Vaso-dilators cut off by section of the lumbar and sacral dorsal roots. At the signal, the central end of the median nerve was stimulated. The rise of pressure is accompanied by constriction in the leg. D, Same experiment, but instead of the median nerve, the central end of a sensory root of the leg area, namely, the sixth lumbar dorsal root, was stimulated. Again there is the usual rise of general blood pressure, but the vessels of the limb itself dilate

This experiment shows that in the I.<*v on reflex there is inhibition of constrictor tone, and the proof is given in Fig. 9 of my paper of 1902, 3, that the dilators are excited, so that reciprocal innervation holds in this case. briefly here ; for further evidence the reader is referred to my two papers (1908, 2 and 3). ^ In pressor reflexes we have rise of arterial pressure produced by contraction of peripheral vessels. This is due, mainly, to excitation of the constrictor centre, which sends impulses causing the smooth muscle of the arterioles, already in a state of moderate tonus, to contract still more. Fig. 239 shows that this takes place, because the leg was supplied only by vaso-constrictors, the dilators having been cut. Figs. 240 and 124 (page 416), however, show that constriction can be detected in pressor reflexes when the organ under investigation is supplied only with dilator fibres. In such cases it must be due to the fact that the muscle of the arterioles was kept in a state of inhibition by impulses from the dilator centre, and that the afferent impulses which excite the constrictor centre also inhibit the dilator centre, thus removing the tonic inhibitory influence on the blood vessels, and allowing them to return to their normal state of. tone. It is to be remembered that, as is pointed out by Sherrington, inhibition cannot be

FIG. 247. EFFECT or STRYCHNINE IN CONVERTING THE DEPRESSOR FALL IN THE The fall is gradually abolished and its place taken by a rise. detected unless there is tonic excitation to be removed. It is, in fact, only in certain states favourable to tonic vascular dilatation, such as high temperature of surroundings and high blood pressure, that it is possible to detect inhibition of dilator tone, apparently on account of the absence of tone in ordinary conditions (see also Fig. 248 below).

When we turn to depressor reflexes, we find it quite easy to show that the constrictor centre is inhibited. Fig. 120 (page 412) shows this, since the dilators had been cut. Excitation of dilators is shown in the case of the chorda tympani nerve, which contains no constrictor fibres, in Fig. 241. Since, however, this nerve contains secretory fibres, which might be supposed to be excited from afferent fibres in the vagus nerve, although no secretion was observed, objection might be taken to this interpretation. Metabolites might be formed by the cells, and these, as we have seen, cause dilatation of the blood vessels. Fig. 242 is, therefore, more convincing, being the reflex from the depressor nerve of the rabbit, which cannot be held to cause reflex secretion.

Fofanov and Chalussov (1913) have confirmed these results, and show that vaso-dilatation in the tongue, the nasal mucous membrane, and the legs occurs when the central end of the depressor is stimulated, although the vaso-constrictor supply has been cut off. Fig. 243 is a copy of one of their curves. The case of the leg is interesting, as I had already pointed out (1902, 3, p. 292), on account of the fact that no dilators, other than the dorsal root fibres, can be detected, so that these must be excited from the centre in an opposite direction to that which would be considered to be the normal one. Fig. 244 is from an experiment of my own, also showing this fact.

Martin and Mendenhall (1915) have shown that there is vaso dilatation in the nasal mucous membrane when the depressor is stimulated, although the vasoconstrictors were cut. In Fig. 245 a diagram of the connections of the two vasomotor centres is given ; this may assist in following the somewhat complex state of affairs. Sherrington (1913, 2, p. 93) interprets these phenomena as being allied to the postural tonus of skeletal muscle. The automatic tonus of the arterial wall is postural as regards the contained blood. As it is only under special conditions that flexor tonus can be obtained, so it appears that tonus of the vaso-dilator centre is not usually to be detected.

At the signal, the ot-Mtnil end of the median nerve was stimulated. There was only a slight rise of blood pressure, because the animal had been eviscerated. Constriction of the ear is shown, preceded by slight dilatation. Same experiment as in Fig. 248, but after the injection of strychnine. Stimulation of the median m-rvc caused ililntati'ni of the ear, accompanied by a slight fall of arterial prf*Mirc. Loven Reflexes. — An interesting form of local vascular reflex was first described by Loven (1866). When the central end of the great auricular nerve, the sensory nerve of the ear in the rabbit, was stimulated, it was noticed that, although vaso-constriction was produced in other organs, in the ear itself vasodilatation occurred. A similar effect was obtained in the leg. Fig. 246 gives two tracings of this latter effect. It appears, thus, that an active organ may bring about a better blood flow to itself, not only by raising the general blood pressure, but by a local vaso-dilatation. I showed that double reciprocal innervation holds also in these reflexes (1902, 3, p. 292, and 1908, 2, pp. 351-353) ; since it appears that the dilators to the ear are probably antidromic in nature- (see Bayliss, 1906, 3, p. 330), we have evidence of another case of reflex stimulation of dorsal root sensory fibres.

The usual effect of strychnine in converting inhibition into excitation is shown in Fig. 247 to apply to the vasomotor centres. In this figure, the effect of gradually increasing doses in converting the depressor fall into a rise is seen. In the further analysis of the action of this drug I met with inexplicable results, until I realised that it must convert, not only the inhibition of the constrictors into an excitation in depressor reflexes, but also that of the dilator centre in pressor reflexes. Thus the vaso-dilators may be excited in a pressor reflex after strychnine, and one obtains conversion of constriction by inhibition of dilator tone into dilatation by excitation of the dilator centre, as shown in Figs. 248 and 249.