THE PHARMACOLOGICAL ACTION OF HARMALINE. 



257 



almost as important as arrest of the respiration in causing death. In the case of 

 smaller lethal doses, where death is clearly due to respiratory failure, the heart rate is 

 diminished soon after injection to a certain extent, and tends to remain at this point 

 till the respirations fail. For example, in Experiment 1 8, where a rabbit received a dose 

 which killed in three hours, the cardiac impacts were reduced from 46 to 27 per ten 

 seconds in twenty minutes, and were still 27 per ten seconds two hours later. The 

 heart is always arrested in diastole. In several experiments in which the heart 

 continued to beat after arrest of the respirations, the right vagus was exposed, and 

 stimulation of it with the coil at 70 mm. to 90 mm. was found to arrest the heart-beats. 



Further experiments were made to ascertain the action of harmaline on the isolated 

 heart, the frog's heart being used. 



In a first series of experiments the heart was perfused in situ through the hepatic 

 vein, the perfused fluid escaping through the cut aorta ; and in a second series the 



*'<*t *77me = Mint/tcS 



A-27 



Fig. 3. 



isolated ventricle alone was perfused by means of Schafer's frog-heart plethysmograph. 

 Only the latter series need be described, as the results were similar in both. As the 

 nutrient solution and as the solvent for harmaline a mixture of defibrinated ox blood 

 (one part) and Ringer's solution (two parts) was used. The bulb of the plethysmograph 

 which contained the heart was filled with Ringer's solution, and the contractions of the 

 ventricle were recorded by means of an air-piston recorder attached by a rubber tube to 

 the brass cylinder. 



Experiment 27 (fig. 3). — Strength of solution, 1 in 2000. 



A solution of 1 in 2000 within one minute arrested the contractions of the ventricle 

 in almost complete systole (fig. 3). Two minutes later the normal solution was turned 

 on, and the heart slowly dilated till it reached the condition of relaxation normal to the 

 end of diastole, whereupon it again resumed beating. The contractions gradually 

 improved till in fifteen minutes the rate and excursus were practically the same as 

 before harmaline. A second introduction of the harmaline solution produced the same 

 effect as before. 



