THE CIRCULATION OF THE BLOOD 32; 



still in diastole for a few seconds, and secondarily increased both in fre- 

 quency and force beyond the normal. If the vagus nerves be first divided 

 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- 

 omc, 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 them and suspending 

 their normal 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 accelerating 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 their terminal 

 fibers. 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 ^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 th e 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. 



