FiTCHETT. — Physiological Action of Tut in. 321 



Marshall (24) found that tutin diminished the number of heart-beats 

 and increased the frequency of respiration. 



As coriamyrtin belongs, pharmacologically, to the picrotoxin group, 

 and is therefore closely allied to some of the decomposition-products of 

 digitalixi — e.g., digitaliresin (30) — it was expected that tutin, which is so 

 closely related to coriamyrtin, might show the tonic action on the heart 

 that is characteristic of the digitalis bodies. In frogs and in mammals, 

 where the heart was examined after the breathing had ceased, it was found 

 invariably to be still beating. In one experiment on a cat (Exp. 153) the 

 heart-beat was distinctly audible with the stethoscope for two minutes and 

 a half after respiration had ceased. 



As it had been observed that tutin has apparently no action on_ striped 

 muscle (Exps. 135 to 138), and as no proof was forthcoming that it has 

 any action on unstriped muscle, it was not considered likely that it would 

 manifest any direct action upon cardiac muscle. As it might, however, 

 have some action on the extrinsic and intrinsic nervous mechanism of the 

 heart, it seemed best to begin the study of its action upon the circulation 

 by observing its effect upon the heart of a pithed frog, where one has to 

 consider muscle and intrinsic ganglia only. A number of experiments 

 were undertaken to determine this. Tracings* of the frog's heart-beat 

 were taken in the usual way with a lever arranged to write against a 

 blackened revolving cylinder. In some cases the tutin solution was painted 

 on the surface of the heart ; in others it was injected into a vein or into the 

 heart itself. The results obtained show that the rate of the beat was 

 slightly diminished : thus, in Exp. 140 the rate fell from 37 to 35 beats 

 per minute : in Exp. 141 from 32 to 30-8. then to 28-8. and then to 26-4 

 per minute ; and in other experiments from 20 to 14 and from 20 to 16. 



After injection of tutin the force of the heart-beat was increased, and 

 the beat was not impaired even with a concentration of tutin solution 

 greater than could possibly be reached by absorption of the poison from the 

 stomach in cases where the plant has been eaten. 



An irregularly beating heart was generally improved, the beat becoming 

 regular. So that it may be concluded that tutin has a purely beneficent 

 influence on the heart's contraction. 



Action on Mammalian Circulation. — This was studied by taking tracings 

 of the blood-pressure from one or other carotid arte^ry, and noting the effect 

 of injections of tutin solution into the jugular vein. The animal was anaes- 

 thetised (chloroform and paraldehyde) during the experiment, and was 

 not allowed to regain consciousness. It was found that injections of tutin 

 solution (0-5 per cent.) caused a rise of pressure : thus in Exp. 143 the 

 initial pressure was 3 in. ; in the course of an hour, during which the 

 animal received nearly 10 mlgm. tutin, the pressure rose gradually to 

 4|in."ln some cases the vagi were divided before the drug was injected, 

 but without affecting the result. The rate with which the blood-pressure 

 rises is proportional to the size of the dose given. In one experiment 

 (Exp. 145), where the abdomen had been opened and its contents handled, 

 a reflex cardiac inhibition seemed to be set up, for the tutin injection in 

 this case caused a marked fall in pressure, which was followed by a rise 

 on division of the vagi. It appears, therefore, that tutin increases the 



* As the tracings had to be sent to Edinburgh with the original thesis, it is im- 

 possible to reproduce them here, and this portion of the work has therefore been sum- 

 marised, and technical details have been omitted. 

 11— Trans. 



