1909.] Observations on the Rate of Action of Drugs, etc. 207 



set by the point at which heat coagulation takes place. But the matter 

 is not quite so simple. We find tiiat with rising temperature the con- 

 tractility (as tested by induction shocks, which are the shortest possible 

 stimuli) vanishes before heat contraction appears. 



There is, in fact, after a first augmentation, a change of an anti-excitatory 

 or inhibitory character, a true heat paralysis of the relaxed muscle before 

 the more profound abolition attributable to heat coagulation.* If the rise 

 of temperature does not go beyond a certain limited point, this heat 

 inhibition is temporarily followed by perfect recovery. Beyond this point, 

 i.e. if coagulation has occurred,! there is no recovery of contractility. In the 

 two examples below the temporary effect has occurred with a rise to 34° 

 — the permanent effect after a rise to 40°.:J: 



As regards the lower limit, we satisfied ourselves that the temperature 

 could be lowered to at least 0° without abolition of contractility, and in 

 our subsequent experiments we did not lower the temperature below 7°, 

 so that in all certainty any retardation observed at 7° was retardation of 

 chemical change as regards the drug and not the simple effect of cold 

 without drug. Thus, e.^., in the experiment of November 12 (fig. 1), we have 

 an undiminished contraction at 0° for at least half an hour ; the muscle 

 undrugged does not lose contractility until congelation actually sets in ; this 

 occurs at — 0°-6 to —1°. 



The variation of chemical change with temperature is most simply 

 expressed by Esson's formula§ 



KT„/KT, = (Ti/Tor, (1) 



which for our purposes becomes 



Lo/Li = (Ti/To)-, (2) 



or simply log Lo — log Li = 7« (log Ti — log To), (3) 



in which Lq and Li are the lengths of time required for the abolition of 



* "The Effect of Heat upon the Electrical State of Living Tissues,'' 'Roy. Soc. Proc.,' 

 vol. 81, B, p. 303, 1909. 



t We do not commit ourselves to the statement that heat-coagulation is an entirely 

 irreversible change. On the contrary, we think that slight degree of such change in the 

 living body can be entirely effaced. 



\ It has been observed that the contractility of a frog's muscle, suspended in saline 

 (0'5 per cent.) solution increases rapidly with rise of temperature from 28° up to 45°, the 

 maximum point. If the muscle be immersed directly in saline solution at 45°, the 

 contraction is instantaneous. Max Verworn, ' Allgemeine Physiologie,' 1897, p. 398. 



§ 'Phil. Trans.,' A, 1895, vol. 186, p. 861. Esson's formula has been shown in other 

 cases to accord better with observed results than does that of Arrhenius — 



