408 SIR THOMAS R. FRASER AND MR ALISTER T. MACKENZIE ON 



G. Summary of the Pharmacological Action of Strophanthus sarmentosus. 



A. The minimum-lethal dose of Strophanthus sarmentosus is almost the same for rabbits 



and cats ; for frogs it is twice as great and for rats 200 times as great as for rabbits. 



B. The predominating features in the action are the effects on the heart and skeletal 



muscles. 



C. The spinal reflex disappears a considerable time after the administration of lethal 



doses of the extract, and not until the heart and respirations had been much 

 affected. This disappearance is due not only to reduced blood-supply but also 

 to a direct action on the cord. When applied to the skin of frogs, the extract 

 is capable of temporarily abolishing the function of sensory nerves in strong 

 solutions, such as from 1 in 1000 to 1 in 500. Slight dilatation of the pupil 

 accompanies the anaesthesia produced by placing such solutions on the eyeball of 

 warm-blooded animals. 



The function of motor nerves is slowly impaired owing to the action of the 

 extract on the nerve-ends, and, much later, it is abolished. Before abolition of 

 function, fibrillary twitches occur in the muscles. The occurrence of these 

 twitches is prevented by paralysing the nerve-ends with curara. 



D. Under the influence of S. sarmentosus, shortening of skeletal muscles is produced 



and, later, fibrillary twitches become conspicuous. When these twitches have 

 disappeared, the contraction of the muscle under stimulation is more gradual, 

 the amount of contraction is less, and the relaxation of the muscle is slower than 

 before ; stronger stimuli are needed to produce contraction ; and, soon, the 

 strongest direct electrical stimulation fails to cause contraction of the muscle. 

 At this time, the muscle is pale, rigid and acid in reaction. 



E. The effects of the extract on the heart are the most important of those produced. 



Small doses tend to produce a diastolic type of change, and large doses a 

 systolic type. This applies equally to application of S. sarmentosus to the outer 

 surface of the heart and to its administration through the blood-stream. With 

 small quantities, the rate of the heart's contractions is slowed, and the size of 

 the diastolic as well as of the systolic movements of the ventricles and auricles 

 and the strength of the systolic contractions of both are increased. These 

 changes are produced when a dilution of even 1 in 500,000 is perfused through 

 the heart. The slowing of the heart's rate is partly due to this increased range 

 of movement, but lengthening of the diastolic pause plays an important part 

 in the retardation. 



With large quantities, the heart's contractions may, at first, be modified in 

 the same way as with small quantities, but the diastolic expansions of the 

 ventricles afterwards become reduced, the quantity of blood entering them 

 becomes lessened, and the ventricles finally cease to contract and remain motion- 

 less in extreme systole. Previously to the final standstill, the ventricular pul- 



