726 6. ARSENICALS 



in rats and a large effect in pigs and fowl. Administration of sodium caco- 

 dylate (Liebesny and Vogl, 1923) and arsenite (Knell, 1936) in small doses 

 to human subjects brought about no marked tonic effects, although some 

 increase in erythrocyte and hemoglobin was noted. The question of efficacy 

 of mechanism has never been satisfactorily settled. It has been commonly 

 thought that arsenicals depress catabolic processes, thus shifting the bal- 

 ance toward assimilation, but such a mechanism has never been established. 

 The history of the uses of arsenic by various peoples, especially in Austria, 

 is a fascinating story and well told in the book "Arsenik" by Allesch (1959). 



Theory of the Capillaries as the Site for Arsenical Toxicity 



Arsenite has been thought by many workers to be one of the most potent 

 and specific capillary poisons, and most, if not all, the toxic effects observed 

 to be due to capillary dilatation and damage, and the consequent loss 

 of fluid through them. Indeed, it has been postulated that the beneficial 

 effects believed to result from low-dosage arsenic intake, as described above, 

 are based on vasodilatation and a better supply of blood to the tissues. 

 Certainly one of the most complex and confused problems in the field of 

 the arsenicals is their action on the blood vessels, particularly the capillaries, 

 and the role this may play in causing the symptoms and lesions long recog- 

 nized as characteristic of poisoning. Since this has some bearing on many 

 of the efl'ects of the arsenicals, it will be necessary to determine as far as 

 possible the nature of the vascular action. 



There is no doubt that the arsenicals at sufficiently high levels can 

 relax vascular smooth muscle, cause leakage of plasma into the tissues, and 

 bring about a multiple hemorrhagic state; the pertinent question is whether 

 such actions occur in the usual clinical or toxic doses. We have seen (page 

 713) that arsenicals commonly lower blood pressure following parenteral 

 administration, and it has generally been assumed that this is primarily 

 the result of vasodilatation, although cardiac depression and central vaso- 

 motor inhibition have also been considered. Unterberger and Boehm (1874) 

 claimed that arsenite causes a paralysis of the splanchnic vessels and that 

 they are no longer responsive to nerve stimulation, and others have observed 

 similar effects. Arsenite vasodilatation has been noted in isolated frog 

 legs, rabbit ears, and rabbit kidneys, rather high concentrations being 

 required to give significant changes (Tscherkess, 1926), but Lendle and 

 Reinhardt (1931) could not repeat these results on the frog legs, some res- 

 ponding by dilatation and some by constriction at arsenite concentrations 

 of 0.11-0.77 mM. Elhnger and Schmitt (1933) studied the mesenteric cir- 

 culation of the frog and found that arsenite first accelerated and then slowed 

 the blood flow. A visible change in the capillary walls was thought to occur 

 during the slowing, and diapedesis was observed, so that a direct action 

 on the vessel walls was assumed. No change in the vascular resistance of 



