274 PROFESSOR C. R. MARSHALL ON 



Division of both vagi has relatively little effect on the respiratory action of 

 protocatechyl-tropeine. In many cases the respiration seemed to recover less readily 

 than in animals with uncut vagi ; and in a few cases the respiration did not recommence 

 spontaneously, as it probably would have done if the vagi had been intact. I have 

 observed the same effect after the administration of tetramethyl-ammonium chloride, 

 a substance which acts on the respiration in a manner similar to protocatechyl-tropeine. 



The experiments were made on etherised animals. The blood-pressure was taken 

 from the common carotid artery, and the injection made into the external jugular 

 vein in cats and the facial vein in rabbits. The respiration was recorded in most 

 experiments by means of a phrenograph with a tube connection to a tambour. 



In a normal animal the largest dose I have been able to give, namely, 0'045 g. 

 intraperitoneally to a rabbit weighing 720 g., produced only dyspnoea. The duration 

 of action of this dose and its influence on the frequency of the respiration is shown 

 in the following table : — 



Time in minutes 

 after injection 



10 20 25 30 40 50 60 90 120 



I 5 



No. of respirations I ^ M g7 153 lg5 135 m m 1Q5 7g g4 

 per minute ) 



When injected into the dorsal lymph sac of winter frogs, 0*04 mg. per gramme 

 body-weight caused slight slowing of respiration, but no other obvious symptoms ; 

 0*08 mg. per gramme body- weight induced marked slowing of the respiration, which 

 also took on a periodic character, groups of a bout six respirations being followed by an 

 interval up to half-minute duration of no breathing ; there was also some muscular 

 depression; 0"16 mg. per gramme body- weight caused almost complete cessation of 

 respiration and muscular paralysis; and 0"24 mg. per gramme body-weight eventually 

 produced complete paralysis of the respiration and death. As an example, the effect 

 after the injection of 0*16 mg. per gramme body- weight may be taken. In this 

 experiment the frequency of the respirations fell to one-half in ten minutes, to one- 

 eighth in twenty minutes, and to one-twentieth in seventy-two minutes after the 

 injection ; the frog was then pithed. 



Action on Vagal Endings. 



This was determined by observing on the blood-pressure the effect of electrical 

 stimulation of a divided vagus before and after injection of the drug, or the effect of 

 the drug after the injection of pilocarpine. When electrical stimulation was employed 

 the procedure was as follows : the vagus was stimulated at intervals until a practically 

 constant effect was obtained, the drug was then injected into the external jugular or 

 facial vein, and the vagus again stimulated at intervals until an effect as near as possible 

 identical with that previously obtained was reached ; or the injection was made during 

 continued stimulation of the vagus (fig. 2). 



