EFFECTS OBSERVED IN THE WHOLE ANIMAL 729 



from work on other tissues it is likely that lewisite can injure essentially 

 any type of cell. The HCl released from lewisite probably plays no role since 

 lewisite oxide is equally effective. 



Thus the important question as to the significance of vascular actions 

 in arsenical toxicity must remain unanswered. It has been said to be 

 reasonable for the blood vessels to be selectively affected because they are 

 initially in contact with the highest concentrations of arsenical as it leaves 

 the blood stream, but this applies to any inhibitor given in the same way, 

 particularly the mercurials and heavy metals which are not generally consid- 

 ered capillary poisons. If the vascular smooth muscle is indeed especially 

 susceptible to the arsenicals, this implies that they possess unique metabolic 

 properties; if this is true, further work on this problem would be interesting. 



Some Effects on the Metabolism in Whole Animals 



Certain changes induced in nitrogen, lipid, and respiratory metabolism 

 by the arsenicals, and the accumulation of keto acids in the blood, have 

 been discussed in previous sections. We shall now take up various metabolic 

 effects which may or may not have bearing on understanding the mechan- 

 isms by which the arsenicals exert their toxic actions. Several early workers 

 found that arsenite causes a loss of glycogen from the liver; by administra- 

 tion of high enough doses, essentially all the glycogen can be depleted within 

 3-5 hr. It was further noted that there is sometimes little or no glucosuria 

 accompanying this glycogen depletion. If glucose is given during arsenite 

 poisoning, no glycogen is formed and glucose appears in the urine. Glycogen 

 falls in other tissues but muscle glycogen is fairly resistant. We must note 

 carefully the difference in the responses to large toxic doses and to the 

 small chronic doses such as have been shown to increase weight. Delhougne 

 (1934) reported that with very small doses (0.001 0.003 mg arsenite daily 

 in the food), rats increase in weight and, in contrast to the above obser- 

 vations, the liver and muscle glycogen increase by 34% and 55%, respec- 

 tively, the lipid and nitrogen contents not changing appreciably. We must 

 thus entertain the possibility that small doses can reduce glycogen utiliza- 

 tion, whereas larger doses can by some mechanism stimulate the breakdown 

 of glycogen. 



This situation can be better understood if we look at the changes in 

 the blood glucose of arsenical-treated animals. Changes in the glucose level 

 had been reported early, but the unreliability of the work and the variations 

 in dosage and the arsenical used confused the picture. Almost 100 years 

 ago it was reported that arsenical medication favorably influences the 

 course of diabetes, but subesquent study did not confirm the ability of 

 the arsenicals to prevent induced glucosuria. Van Dyke (1925) found that 

 intravenous arsenite in doses considerably subtoxic (4 mg/kg) causes a 

 distinct hyperglycemia in rabbits and that this occurs after bilateral splanch- 



