158 Prof. T. K. Fraser and Dr. J. Tillie. Gn the [Mar. 23, 



in extreme and permanent systole. The auricles contract for a short 

 time longer, but cannot empty themselves, and become arrested in a 

 dilated state. The heart no longer responds to stimulation, and the 

 muscle of the ventricle quickly acquires an acid reaction. After 

 arrest of the heart, respiration may continue irregularly for so long 

 as an hour, and for a time the frog can jump about actively. 



The action of small doses upon the heart is, in several respects, 

 essentially different from that of large doses. Several hours after the 

 administration of the precise minimum lethal dose, the cardiac pulsa- 

 tions become very slow. The slowing, however, is not due to a 

 lengthening of the systole, but to a great prolongation of the diastole, 

 and of the succeeding pause in the heart's action. Gradually, periods 

 of standstill occur in extreme diastole, and, when the heart sponta- 

 neously resumes beating, one or more auricular contractions precede 

 those of the ventricle. The systolic contraction is extremely power- 

 ful. The condition of diastolic arrest often lasts many minutes at a 

 time, and finally spontaneous pulsations cease. At this stage, the 

 dilated heart responds, by one or more contractions, to any form of 

 stimulation, but, if the stimulation be frequently repeated, the re- 

 laxation after each contraction becomes less and less, and the ven- 

 tricle slowly passes into moderate, but permanent, systole. During 

 these events, the inhibitory function of the vagus is not only retained, 

 but increased. The diastolic arrest of the heart is not dependent 

 upon " inhibition," however, for the condition is neither removed 

 nor prevented by the administration of atropine. The accelerator 

 action of the vagus is retained. The diastolic arrest is apparently 

 due, therefore, to a direct action of the poison upon the motor ganglia 

 and muscle of the heart. 



The action upon the blood-vessels was found to be very slight. One 

 part of the crystalline active principle in 10,000 parts of normal 

 saline solution (0"75 per cent.) produced, when circulated through 

 the vessels of a pithed frog, about the same effect as the pure saline 

 solution, whereas 1 part of Merck's purest digitalin (soluble in water) 

 in 50,000 parts of normal saline solution produced an extreme and 

 rapid reduction in the calibre of the vessels. This difference in action 

 upon the vessels is much accentuated by the fact that the lethal power 

 of the digitalin in frogs was found to be only about l/50th of that of 

 the active principle of the Acokanthera wood. 



In blood pressure experiments upon rabbits, the repeated adminis- 

 tration of small non-lethal doses by injection into the jugular vein 

 produced a remarkable slowing of the pulse, the vertical height of 

 each pulse curve indicating at the same time a great increase in the 

 force of the ventricular contraction. The blood pressure was usually 

 found not to be increased, and, when increased, was evidently not the 

 cause of the slow pulse. When rise of blood pressure from asphyxia 



