100 Distribution and Action of Soluble Substances in Frogs. 



Animals in which strychnine produced an early definite depression and 

 a paretic state are survived by the controls. 



Strychnine, then, is readily distributed in the cardiectomised animals and 

 produces there vital phenomena similar to those seen in normal frogs, that is, 

 tetanus and paralysis. The paralysis in the cardiectomised frogs is central 

 and is not due to fatigue. The occurrence of a violent tetanus in these 

 animals refutes conclusively the theory of Verworn, that the paralysing action 

 of strychnine is due to its paralysing effect upon the heart. 



Morphine. — When about 10 or 15 mgrm. of morphine have been injected 

 into a normal frog, no effects will be noticed until a few days later, when it 

 may develop a tetanus. A cardiectomised frog, however, reacts to morphine in 

 an entirely different manner. A small dose of morphine, 6 or 8 mgrm. for 

 a medium-sized frog, will bring out a tetanus in 40 or 50 minutes. After 

 a larger dose, the tetanus is preceded by depression and weakness. After 

 a still larger dose, the effect is paralysis with very little evidence of hyper- 

 excitation. In short, in cardiectomised frogs morphine affects the central 

 nervous system very rapidly, the effects being nearly like those of 

 strychnine, that is, tetanus with smaller doses, and paralysis with larger 

 doses. The most plausible explanation of the surprising fact is, perhaps, 

 this : — The central circulation receives secretions from all organs and tissues, 

 and conveys them rapidly to all parts of the body ; the action of each 

 secretion, therefore, and of all substances taken up into the circulation, 

 is modified by the neutralising effects of various secretions. In the absence 

 of the circulation there are no such modifying effects to interfere with the 

 specific action of some substances. 



The experiments demonstrate that in the absence of the central 

 circulation substances may be distributed through the body by a mechanism 

 which in some instances may act even more promptly than the cardiac 

 mechanism. In contradistinction to the central apparatus we may 

 designate the distributing agent in question as a peripheral mechanism. 

 The path of distribution employed by this mechanism can be nothing else 

 than the tissue spaces. About 15 years ago we* insisted that these are 

 more or less efficiently connected throughout the body, and present a 

 unity, a system of their own. A similar peripheral mechanism, working 

 through a similar path, is probably active in the distribution of mesolymph 

 in animals still without a cardio-vascular apparatus. In animals possessing 

 such an apparatus the peripheral mechanism may perhaps have the 

 significance of a phylogenetic phenomenon. 



* Adler and Meltzer, 'Jour, of Exper. Med.,' 1, 512, 1896. 



