Abstract
We have observed that 10 to 20 times more tetanus antitoxin given intravenously is required to protect guinea pigs and rabbits against a multiple lethal dose of the toxin injected intramuscularly than intravenously. Table I gives the results of a representative experiment.
In further experiments we found that free antitoxin was present in the blood of the intramuscularly-injected animal at the time of death. These observations, we believe, have an important bearing on the pathogenesis of tetanus. They show that the death of the animal cannot be due to toxin reaching other muscles or the central nervous system by way of the circulating blood.
After excluding the Danysz phenomenon as a factor in our results we were faced with the alternative that either, contrary to Abel's 1 , 2 , 3 conception, tetanus toxin reaches the central nervous system by way of the peripheral nerve, or that a secondary toxic substance is formed in the muscle which is not neutralized by antitoxin. The first substance we suspected was acetylcholine. This phase of the work is still going on.
In searching for this hypothetical substance, toxin and muscle were mixed in vitro. It was found that when injected intramuscularly, the “muscle toxin” was 4 to 8 times more lethal than the pure toxin and 8 times more effective in causing local tetanus. In Table II we present a protocol of one of the many experiments we have carried out with this phenomenon.
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