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this primary decrease is not so marked and the inference is that the alkaloid 

 primarily stimulates the cardio-inhibitor center and increases its normal 

 function and perhaps the terminal branches of the vagus fibers, the pre-gangli- 

 onic, as well. After the secondary increase in the rate is established stimulation 

 of the vagus trunk fails to inhibit the heart, though stimulation of the intra- 

 cardiac ganglia is at once followed by the usual inhibitor phenomenon, arrest 

 of the heart in diastole. For this reason it is believed that nicotin acts on the 

 peripheral terminations of the pre-ganglionic fibers of the vagus as they 

 arborize around the intra-cardiac ganglia, depressing the receptor sub- 

 stance and suspending its function, that of conducting nerve impulses from 

 the vagus to the ganglion cells. Since stimulation of the pre-ganglionic 

 fibers of the accelerator apparatus fails to accelerate the rate of the heart- 

 beat, though stimulation of the post-ganglionic fibers has the usual ac- 

 celerating effect, the inference is that nicotin acts upon and suspends the 

 conductivity of their terminal branches in the ganglia. The acceleration 

 of the heart must therefore be attributed either to a stimulation of the 

 post-ganglionic fibers or of the cardiac muscle itself (Cushny). 



Pilocarpin and Muscarin. These alkaloids, whether administered in- 

 ternally or applied locally to the heart, diminish the frequency and the 

 force of the beat to such an extent that it very shortly comes to rest in dias- 

 tole. For the reason that the internal administration or the local applica- 

 tion of atropin in proper doses, which has a depressive action on the intra- 

 cardiac cell terminations, removes the inhibition and restores the normal 

 rhythm, the inference is drawn that both these alkaloids either increase the. 

 irritability of the nerve-cells or heighten the conductivity of the receptor 

 substance. The return of the heart-beat is attributed to a decline in 

 irritability to the normal level in consequence of the antagonistic action 

 of the atropin. 



Digitalin. The administration of digitalin gives rise to effects the 

 character and extent of which vary in different animals. In the frog, as a rule, 

 the only effect produced is a gradual increase in the duration and force of the 

 ventricular systole, with a corresponding decrease in the duration of the dias- 

 tole, until the heart comes to rest in the systolic state. As this effect is 

 observed after division of the vagus trunk and also after the suspension of 

 the activity of the intra-cardiac cell-fibers by atropin, it is evidently due to a 

 direct stimulation of the heart-muscle. In some instances, however, the 

 opposite effect is produced, viz. : a gradual increase in the length of the diastole, 

 a decrease in the duration of the systole, until the heart comes to rest in the 

 diastolic state. As this effect arises only when the vagus nerve is intact it is 

 very probably due to a stimulation of the cardio-inhibitor center and a con- 

 sequent increase of its functional activity. Though either effect may be 

 produced in the frog the predominant effect is the increase in the contrac- 

 tion of the heart-muscle rather than an inhibition of the beat. 



In mammals both effects are observed, viz. : a diminution in the rate of 

 the beat, a lengthening of the diastole and an increase in the vigor of the 

 systole, which are evidently due to a simultaneous stimulation of the cardio- 

 inhibitor center and of the cardiac muscle. Digitalin thus expends itself on 

 two opposing mechanisms; as to which gains the ascendency will depend on 

 the dosage and the character of the animal. 



