142 



W. J. V. OSTERHOUT 



Another investigation relates to anaesthesia. Much uncer- 

 tainty exists as to the mode of action of anaesthetics, and particu- 

 larly as to their effects on permeabihty. Most writers hold 

 that anaesthetics increase permeability, but some have taken the 

 opposite view. 



Without quantitative methods it would not have been possible 

 to give a definite answer to this question. It is, however, very 

 satisfactorily cleared up by means of the electrical method. 

 Very low concentrations of anaesthetics produce little or no effect, 

 but when the concentration is increased a point is soon reached 

 at which a decided decrease of permeabihty occurs. As the con- 

 centration increases still further this decrease becomes more pro- 

 nounced (and is maintained for several hours if the material is 

 allowed to remain in the anaesthetic). This change of per- 

 meability is completely reversible and involves no injury. 



If the concentration be still further increased the permeability 

 at first decreases and quickly falls to a minimum: the permea- 

 bility then rises rapidly to a point far above the normal, where 

 it may remain stationary for a time, but if the concentration be 

 sufficiently high it continues rising until death ensues. 



It is therefore evddent that typical anaesthetics, such as ether 

 chloroform, alcohol and chloral hydrate, increase or decrease 

 permeability, depending on their concentration. 



A question of great importance is: which of these effects is 

 responsible for anaesthesia. It seems that the "answer to this 

 question is clearly indicated by the fact that the decrease of 

 permeability is quickly and easily reversible, while the increase 

 of permeabihty is not. The increase of permeability is in most 

 cases almost completely irreversible; only exceptionally, when 

 the increase has gone but a little way, can a partial reversal be 

 secured. 



The distinctive mark of an anaesthetic is the reversibiUty of 

 its action, and it is quite e\adent that we have in this experiment 

 two distinct things, the anaesthetic effect which is associated 

 with a reversible decrease of permeabihty, and the toxic effect, 



