A CTION OF CER TAIN POISONS. 2 2 3 



act in the same way as sodium salts, namely, increase the strength 

 and length of the contractions, and ultimately bring the apex or 

 ventricle into a condition of systolic standstill. This series includes 

 such poisons as antiarine, digitalin, veratrine, and, to a less degree, 

 atropine. 



Further, my own experiments have shown that, just as the 

 alkaline sodium salt and the lactic acid solution can antagonise each 

 other on the apex muscle, so also muscarine and digitalin 1 can 

 antagonise each other ; and Luchsinger and his pupil Amalie Glause 

 have shown that all the members of the muscarine group behave in 

 the same way to atropine. The evidence, then, is strong that both 

 atropine and muscarine act directly upon the muscular tissue of the 

 heart in opposite directions. What the precise nature of these opposite 

 actions is, whether the poisons form loose chemical combinations with 

 the contractile tissue, as originally suggested by Langley and after- 

 wards by Einger and myself, or whether they act in some other way, 

 is at present unknown. 



The weakening effect of muscarine upon the muscular tissue is shown, 

 not only by the diminution of the strength of the contractions and the relaxa- 

 tion of the tissue, but also by the diminution of the conductivity. 



I know no more striking experiment to show the opposing action of 

 muscarine and atropine, than is afforded by a strip from the auricle of the 

 tortoise, which has been taught to respond vigorously and well to single 

 induction shocks sent through a pair of electrodes applied to one end of the 

 strip. With each induction shock a strong contraction occurs through the 

 whole strip. Now, let a little muscarine solution drop over the strip; immediately 

 the contraction is seen to consist of two parts first, that of the small piece of 

 muscle between the electrodes, and then, quickly following, the rest of the 

 muscle ; a little later, the pause between the contraction of the two parts of 

 the muscle becomes very marked, and a partial block often occurs, so that only 

 every second contraction of the piece between the electrodes is followed by a 

 contraction of the rest of the strip, that contraction itself being weaker ; finally, 

 the block is complete, and the only part which contracts is the small piece 

 between the electrodes. Now, apply a drop of atropine solution over the strip ; 

 like magic each contraction passes the block, and in a remarkably short time 

 the whole strip contracts to every induction shock as strongly and rapidly as 

 before. We see, in fact, in the strip a miniature representation of the action 

 of the two poisons on the whole heart. 



Again, the presence of the coronary nerve in the tortoise enables the 

 question, whether muscarine applied to the sinus stimulates inhibitory 

 mechanisms there, to be tested by means of the electrical changes which 

 occur in the isolated quiescent auricular muscle, when the sinus and 

 therefore the fibres of the coronary nerve are stimulated. I find 2 that, 

 whereas a crystal of salt applied to the sinus will produce the same 

 electrical variation as stimulation of the vagus nerve, muscarine applied 

 to the sinus produces no effect whatever; there is not the slightest 

 indication of any stimulating action. 



It has been further argued by Kobert 3 that, as a dose of muscarine, 

 which will easily cause standstill when applied to the sinus, will not 

 arrest the contractions of the isolated ventricle, therefore it acts 



1 Gaskell, Journ. Physiol., Cambridge and London, 1880, vol. iii. p. 12, PI. III. 



" Ibid,.. 1887, vol. viii. p. 404. 



3 Arch. f. cxper. Path. u. Pharmakol . , Leipzig, 1885, Bd. xx. S. 92. 



