367 



less strong ones a slow and gradual effect; while below a certain 

 concentration it can no more occur. 



If the poisoning-process in a calf-nmscle, which is left in situ is 

 studied here — again with a stimulation-interval of three minutes — 

 the process mentioned sub 1 is never observed, because the vera- 

 trin-concentration in the blood never reaches a sufllcient heigiit. 

 On emploj'ing large doses (e.g. 15 mgr. per 50 Gr. frog) the heart 

 is arrested after a short time as Boehm ') describes it and the muscle 

 is in no other relation — not considering a more intensive contact 

 with the veratrin-solution — than in a muscle-trough of Keith 

 Lucas, filled with a solution of the concentration at which the 

 process mentioned sub 2 occurs; the conduct of the muscle is indeed 

 in absolute accordance with this. On using smaller doses (1 — -2 mgr. 

 per 50 Gr. frog), the heart, at least during the first hours after 

 poisoning, keeps beating, only gradually diminishing its frequency; 

 consequently the quantity of veratrin carried to the muscle is 

 steadily increased and it should be borne in mind, that when the 

 veratrin-concentration exceeds a definite threshold, the second effect 

 of veratrin mentioned above will make its influence felt, i.o.w. 

 the poisoning will seem less intensive: conversely every contraction 

 will abolish part of the veratrin-effect and it may be supposed that 

 in this way interference takes place between the influence of the 

 two factors, determining the effect of the rate of poisoning, viz. the 

 application and the rendering inactive of veratrin, when their two 

 causes, i.e. the heart-action and the lapse of time between two con- 

 tractions, occur in a definite proportion. As a result of this inter- 

 ference a periodicity occurs in the poisoning-process, i.e. the effects 

 of stronger poisoning (higher, more prolonged second top) vary with 

 those of less strong poisoning. At length the regularity of these 

 oscillations is interrupted, because the heart-action diminishes under 

 influence of the effect of the poison and the relation above-mentiond 

 exists no more. 



A constant poisoning in a muscle in situ can only then be obtained 

 when the poison is applied without interference of the heart, e.g. 

 by subcutaneous muscular injection (Buchanan)'). 



2. Combination of veratrin and curare. 



De Boer') communicates the possibility of leaving only the second 

 shortening by simultaneous application of veratrin and curare. He 



1) Arch. f. exp. Path. u. Pharm., 71, 1913. • 



2) Journ. of Physiol. 1899. 



3) Contributions Amsterdam 1914 — 15 and Zeitschr. f. Biol. 65. 



