§ 410. Effects on Animals—Physiological Action.—Gelsemine acts powerfully on the respiration; for example, Drs. Sydney Ringer and Murrell[461] found, on operating on the frog, that in two minutes the breathing had become distinctly slower; in three and a half minutes, it had been reduced by one-third; and in six minutes, by one-half; at the expiration of a quarter of an hour, it was only one-third of its original frequency; and in twenty minutes, it was so shallow and irregular that it could no longer be counted with accuracy. In all their experiments they found that the respiratory function was abolished before reflex and voluntary motion had become extinct. In several instances the animals could withdraw their legs when their toes were pinched, days after the most careful observations had failed to detect the existence of any respiratory movement. The heart was seen beating through the chest wall long after the complete abolition of respiration.
[461] Lancet, vol. i., 1876, p. 415.
In their experiments on warm-blooded animals (cats), they noticed that in a few minutes the respirations were slowed down to 12 and even to 8, and there was loss of power of the posterior extremities, while at short intervals the upper half of the body was convulsed. In about half an hour paralysis of the hind limbs was almost complete, and the respiratory movements so shallow that they could not be counted. In the case of a dog, after all respiration had ceased tracheotomy was performed, and air pumped in: the animal recovered.
Ringer and Murrell consider that gelsemine produces no primary quickening of the respiration, that it has no direct action on either the diaphragm or intercostal muscles, that it paralyses neither the phrenic nor the intercostal nerves, and that it diminishes the rate of respiration after both vagi have been divided. They do not consider that gelsemine acts on the cord through Setschenow’s inhibitory centre, but that it destroys reflex power by its direct action on the cord, and that probably it has no influence on the motor nerves. Dr. Burdon Sanderson has also investigated the action of gelsemine on the respiration, more especially in relation to the movements of the diaphragm. He operated upon rabbits; the animal being narcotised by chloral, a small spatula, shaped like a teaspoon, was introduced into the peritoneal cavity through an opening in the linea alba, and passed upwards in front of the liver until its convex surface rested against the under side of the centrum tendineum. The stem of the spatula was brought into connection with a lever, by means of which its to-and-fro movements (and consequently that of the diaphragm) were inscribed. The first effect is to augment the depth but not the frequency of the respiratory movements; the next is to diminish the action of the diaphragm both in extent and frequency. This happens in accordance with the general principle applicable to most cases of toxic action—viz., that paresis of a central organ is preceded by over-action. The diminution of movement upon the whole is progressive, but this progression is interrupted, because the blood is becoming more and more venous, and, therefore, the phenomena of asphyxia are mixed up with the toxical effects. Dr. Sanderson concludes that the drug acts by paralysing the automatic respiratory centre; the process of extinction, which might be otherwise expected to be gradual and progressive, is prevented from being so by the intervention of disturbances of which the explanation is to be found in the imperfect arterialisation of the circulating blood. Ringer and Murrell have also experimented upon the action of gelsemine on the frog’s heart. In all cases it decreased the number of beats; a small fatal dose produced a white contracted heart, a large fatal dose, a dark dilated heart; in either case arrest of the circulation of course followed.
§ 411. Effects on Man.—The preparations used in medicine are the fluid extract and the tincture of gelsemine; the latter appears to contain the resin of the root as well as the active principle. There are several cases on record of gelsemine, or the plant itself, having been taken with fatal effect.[462] Besides a marked effect on the respiration, there is an effect upon the eye, better seen in man than in the lower animals; the motor nerves of the eye are attacked first, objects cannot be fixed, apparently dodging their position, the eyelids become paralysed, droop, and cannot be raised by an effort of the will; the pupils are largely dilated, and at the same time a feeling of lightness has been complained of in the tongue; it ascends gradually to the roof of the mouth, and the pronunciation is slurred. There is some paresis of the extremities, and they refuse to support the body; the respiration becomes laboured, and the pulse rises in frequency to 120 or 130 beats per minute, but the mind remains clear. The symptoms occur in about an hour and a half after taking an overdose of the drug, and, if not excessive, soon disappear, leaving no unpleasantness behind. If, on the other hand, the case proceeds to a fatal end, the respiratory trouble increases, and there may be convulsions, and a course very similar to that seen in experimenting on animals. Large doses are especially likely to produce tetanus, which presents some clinical differences distinguishing it from strychnine tetanus. Gelsemine tetanus is always preceded by a loss of voluntary reflex power, respiration ceases before the onset of convulsions, the posterior extremities are most affected, and irritation fails to excite another paroxysm till the lapse of some seconds, as if the exhausted cord required time to renew its energy; finally, the convulsions only last a short time.
[462] See Lancet, 1873, vol. ii. p. 475; Brit. Med. and Surg. Journ., April 1869; Phil. Med. and Surg. Reporter, 1861.