The experiments reported in this article are in full agreement with the facts known about the action of Ca and Mg salts in tetanic animals. In the concentrations used here both Ca lactate and Mg lactate suppressed the muscular convulsions in the tetanic salamander larvæ. The Mg lactate, however, appears to be more effective than the Ca lactate. At any rate the suppression of the tetanic convulsions does not seem to be a specific action of the calcium.
The most important result seems to be the fact that the salts used, though they prevented the muscular convulsions, did not prevent the other symptoms of tetany which in the salamander larvæ are very definite and constant. The permanent spasmodic contractions and the paralysis of the muscles developed in spite of the presence of the Ca and Mg, Furthermore, the muscular contractions and the paralysis developed even in such thymus-fed animals in which the convulsions had been suppressed completely; this was the case in one of the animals of the Mg series.
From the experiments of Biedl and others it is likely that the tetanic convulsions are due to lesions of the central nervous system, since convulsions of a leg can be prevented by isolating it from the central nervous system by cutting the nerves which connect the muscles with the central nervous system. Evidently these lesions of the central nervous system are the chief factor in tetany, while the convulsions of the muscles are only an effect. In the larvæ of salamanders these lesions find a definite expression in the permanent paralysis of almost the entire muscular system.
In the writer's opinion, MacCallum's hypothesis that the tetany toxin has a special affinity for Ca, thereby diminishing the Ca content of the organism, cannot be disproved at present. But the present experiments seem to prove, first, that the tetany-producing substance causes permanent lesions of the nervous system, which lead to permanent spasmodic contractions and paralysis of the muscle even in the absence of tetanic convulsions, and second, that these cannot be prevented by either Ca or Mg. For the most part they result in an early death of the animals no matter whether or not Ca or Mg has been applied.
In connection with this fact we wish to mention Biedl's claim that no one has yet succeeded in prolonging the life of parathyroidectomized animals by the application of Ca. From MacCallum's paper, on account of the lack of controls, it cannot be seen whether his parathyroidectomized dogs lived longer with Ca treatment than without.
That in spontaneous tetany Ca treatment may effect a cure, as is evident from the report by Howland and Marriott, does not prove that in this case Ca has inhibited tetany as a disease. In spontaneous tetany the period of the action of the tetany-producing substance may be a very short one and the mere prevention of the tetanic convulsions may keep the patient alive until normal function of the glands involved has been restored. The pathological changes which the central nervous system undergoes in this short period may not be severe enough to endanger the life of the patient after the cessation of the action of the tetany toxin.
In the light of the facts presented our experiments lead to the following conclusions:
1. The thymus gland excretes a tetany-producing substance which in the normal animal is antagonized in an unknown way by the parathyroids.
2. In animals devoid of parathyroids (salamander larvæ, parathyroidectomized mammals) this substance may, according to MacCallum, reduce the Ca content of the organism; but by far the most dangerous and important quality of this substance is its highly injurious effect upon the central nervous system, which causes permanent spasmodic contractions of the muscles and paralysis of almost the entire muscular system.
3. It is possible to prevent the muscular contractions by introducing Ca salts into the body, though this can be done more effectively by means of Mg salts.
4. No substance, however, has been found so far to antagonize the tetany toxin and to prevent the development of the lesions of the central nervous system caused by the tetany toxin.
5. This explains why in spite of the application of Ca or Mg and in spite of the suppression by these substances of the tetanic convulsions the other symptoms of tetany develop and frequently lead to the death of the animal.
6. Accordingly the most important function of the parathyroids is to prevent the tetany toxin, by antagonizing it, from coming into contact with the central nervous system.
Pre-existing neuronal pathways in the leg imaginal discs of Drosophila