RESTORATIVE EFFECT OF SALTS OF MAGNESIUM AND CALCIUM AFTER LETHAL DOSES OF SODIUM OXALATE.
The experiments presented in this paper brought out the following facts. Intramuscular injections of sodium oxalate into rabbits in doses of 0.18 and 0.2 gm. proved to be invariably fatal, death generally occurring in a comparatively short time. The symptoms consisted in excitation and tonic and clonic convulsions of diminishing strength if death was delayed. Some animals succumbed in the first convulsion. From the experiments in which magnesium or calcium was added, it was evident that massage of the site of the oxalate injection is unmistakably an aggravating factor. In the experiments with the addition of magnesium or calcium, doses of 0.2 gm. of oxalate were used, with or without massage. The character of the effect which follows an addition of magnesium and calcium was studied in animals which received oxalate in doses above the minimal lethal one. Nevertheless, there was practically in all cases clear evidence that the effect of the additional injections was in the nature of an antagonism to the oxalate effects. An injection of 0.6 gm. of magnesium not only alleviated or abolished the excitation and convulsions, characteristic of oxalate poisoning, but also reduced the mortality by 30 per cent. When the dose of magnesium was only 0.4 gm. per kilo of body weight and the site of the injection of the oxalate was not massaged-a condition in which 0.2 gm. of oxalate alone was invariably fatal-the mortality was reduced by 80 per cent. The favorable effect of injections of calcium chloride depended upon the quantity injected and the length of the interval elapsing between the injection of the oxalate and that of the calcium. When the site of the oxalate was massaged and only 5 cc. of the calcium solution were injected, the animals succumbed to the oxalate poisoning. When 10 cc. of calcium were given 1 minute after the oxalate injection, the animals survived. When the site of the oxalate injection was not massaged, then even 5 cc. of the calcium were sufficient to save life. A curative effect of calcium upon oxalate poisoning has been claimed by previous writers. This is not difficult to explain and probably consists in the simple chemical process which can be demonstrated in vitro. Oxalates precipitate calcium salts in vitro and have the same effect within the animal body. By virtue of this precipitation the calcium of the body is reduced below the amount indispensable to maintain life. Loeb said: "It is due to the presence of Ca- (and K-) ions in our blood that our muscles do not contract rhythmically." The convulsive movements in oxalate poisoning may be due at least partly to a reduction of the calcium content of the fluids of the animal body. In our experiments it required an injection of 10 cc. of calcium chloride to restore the calcium content to the indispensable amounts; the injection of 5 cc. was effective only when the site of the oxalate injection was not massaged. The fact that calcium salts are antagonistic to the effects of magnesium salts, which are practically only inhibitory in their nature, does not exclude the possibility that under certain conditions calcium may also exert an inhibitory effect. The following is an instructive illustration. Prolonged perfusion of a nerve muscle preparation with sodium chloride abolishes the irritability of the motor nerve endings; addition of calcium chloride restores it. On the other hand, perfusion with calcium chloride alone promptly abolishes this irritability. In one case it restores the irritability while in the other it inhibits it. It is different with regard to the action of magnesium upon oxalate poisoning. Superficially it seems that there is a direct contradiction between the results reported in a previous communication; and the experiments reported in this paper. The first series of experiments demonstrates that oxalate and magnesium act synergetically, while in the present series evidence is brought forward that magnesium acts antagonistically to the poisonous effects of the oxalate. However, this seeming contradiction may be explained on the assumption that oxalates, especially in larger doses, aside from their calcium-precipitating property, exert by means of a yet unknown factor a further toxic effect which favors the development of excitation and convulsions, which in turn lead to exhaustion and death. The employment of carefully selected doses of a magnesium salt will reduce or abolish the excitation and spastic attacks and thus will prevent exhaustion and hence save life. We may thus say that the favorable antagonistic action of magnesium against large, fatal doses of an oxalate is merely symptomatic in its nature-similar, for instance, to the favorable effect of chloroform upon strychnine, convulsions-while the synergetic action of subminimal doses of magnesium and oxalate may be considered as specific in nature. The precipitating action of the oxalate decreases the calcium content and thus increases the effectiveness of the inhibitory action of the subminimal dose of magnesium.
Gates
F L
FL
Department of Physiology and Pharmacology of The Rockefeller Institute for Medical Research.