This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
This view is to some extent borne out by the different effect produced by a constant current upon these convulsions, according as it is passed transversely or longitudinally through the spinal cord. Ranke found that when passed transversely it has no effect, but when passed longitudinally in either direction it completely arrests the strychnine convulsions, and also the normal reflexes which are produced by tactile stimuli.
Ranke's observations have been repeated by others with varying result, and this variation may, I think, be explained by the effect of temperature. The effect of warmth and cold upon strychnine-tetanus is hat we would expect on the hypothesis of interference. With small doses of strychnine, warmth abolishes the convulsions, while cold increases them. When large doses are given, on the contrary, warmth increases the convulsions, and cold abolishes them.1
We may explain this result on the hypothesis of interference in the following manner :If a small dose of strychnine retard the transmission of nervous impulses so that the inhibitory wave is allowed to fall rather more than half a wave-length, but not a whole wave-length, behind the stimulant wave, we should have a certain amount of stimulation instead of inhibition. Slight warmth, by quickening the transmission of impulses, should counteract this effect, and should remove the effect of the strychnine. Cold, on the other hand, by causing still further retardation, should increase the effect. With a large dose of strychnine, the transmission of the inhibitory wave being still further retarded, the warmth would be sufficient to make the two waves coincide, while the cold would throw back the inhibitory wave a whole wave-length, and thus again abolish the convulsions.
The effect of temperature on the poisonous action of guanidine is also very extraordinary, and is very hard to explain on the ordinary hypothesis, although the phenomena seem quite natural when we look at them as cases of interference due to alterations in the rapidity with which the stimuli are transmitted along nervous structures.
1 Eunde and Virchow, quoted by Eckhard, op. cit. p. 44; Foster, Journal of Anatomy and Physiology, November 1873, p. 45.
Another cause of tetanus that is difficult to understand on the ordinary hypothesis of inhibitory centres is the similar effect of absence of oxygen and excess of oxygen. When an animal is confined in a closed chamber without oxygen, it dies of convulsions; when oxygen is gradually introduced before the convulsions become too marked, it recovers. But when the pressure of oxygen is gradually raised above the normal, the animal again dies of convulsions. This is evidently not the effect of mere increase in atmospheric pressure, but the effect of the oxygen on the animal, inasmuch as twenty-five atmospheres of common air are required to produce the oxygen-convulsions, while three atmospheres of pure oxygen are sufficient. This effect is readily explained on the hypothesis of interference by supposing that the absence of oxygen retards the transmission of impulses in the nerve-centres; so that we get those which ought ordinarily to inhibit one another coinciding and causing convulsions. Increased supply of oxygen gradually quickens the transmission of impulses until the waves first reach the normal relation, and then, the normal rate being exceeded, the impulses once more nearly coincide, and convulsions are produced a second time.1
The effect of various agents also in arresting or inhibiting muscular action suggests the possibility that such inhibition is due to interference with vibrations in muscle. The vibrations of the parts which occur in the muscle during the passage of a constant current have already been mentioned. When a constant current is passed for a length of time and then stopped, tetanic contraction of the muscle occurs and lasts for some time, but it can be at once arrested by again passing the constant current through the muscle.
The idea that coincidence or interference of contractile waves in muscle have much to do with the presence or absence of contraction of a muscle has been advanced by Kuhne, in order to explain the phenomenon observed by A. Ewald. When the sartorius of a frog is stimulated at each end by electric currents passing transversely through the ends, the secondary contraction which can be obtained from it is strongest in the middle of the muscle, while the points exactly intermediate between the middle and the end do not produce any secondary contraction at all. This absence of secondary contraction Kuhne thinks is due to interference, and the powerful secondary contraction from the middle to coincidence of waves.1
1 For other observations on interference as a cause of inhibition, vide Wundt, Untersuchungen zur Mechanik der Nerven und Nervencentren. 1876. (Stuttgart: T. Enke); Ranvier, Leqons d'Anatomie Generale. Annee 1877-78. (Paris: J. B. Bailliere et Fils); and Lauder Brunton 'On the Nature of Inhibition and the Action of Drugs upon it' (Nature, March 1883, and reprint).
Inhibition may also be produced by direct irritation of involuntary muscular fibre. Thus I have noticed, under Ludwig's direction, that stimulation of veins as a rule very frequently causes dilatation at the point of irritation, and if the muscular fibre of a frog's heart be injured by pinching at one point, that point is apt to remain dilated when the rest is contracted. Protoplasmic structures appear to be similarly affected, and the passage of an interrupted current through the heart of a snail will arrest its rhythmical pulsations, although the heart in this animal appears to be a continuous protoplasmic structure and destitute of nerves.2
1 Untersuchungen a. d. Physiolog. Inst, Heidelberg, 1879. Sonderabdruck, p. 40.
2 M. Foster, Pfliiger's Archiv.