EFFECTS ON TISSUE FUNCTIONS 941 



actions of the mercurials on the heart have been well studied but the 

 mechanisms involved, and whether these actions involve metabolic distur- 

 bances, are not known. Hepp (1887) observed that the toxic effects of the 

 organic mercurials differ from those produced by Hg++, and that ethyl- 

 Hg++ stops the frog heart in diastole. Dreser (1893) studied the cardiac 

 effects of several complexes of Hg++, both in vivo and on perfused isolated 

 frog hearts. Cardiac depression was noted after injection of around 2.5 mg 

 of the rhodanate, succinimide, and cyanide complexes of Hg++, and stand- 

 still of the isolated heart was brought about by 0.45 mM of the thiocyanate 

 complex. These and other early investigations showed only that the heart 

 can be depressed by mercurials and that the relative potencies depend on the 

 substances with which the Hg++ is complexed. For example, Miiller et al. 

 (1911) showed that compounds of the type R — Hg — OH or R — Hg — CN are 

 around 10 times as cardiotoxic in cats as compounds of the type R — C — 

 Hg — C — R in which the Hg is bonded to two C atoms, and that the toxicity 

 is related to the rate at which these compounds react with sulfide. The first 

 serious study of the effects of the mercurials on the heart was undertaken 

 by Salant and his co-workers in Georgia from 1921 to 1931, the results of 

 which will be discussed throughout the following sections. 



(A) Isolated heart preparations. The effects of the mercurials depend on 

 the species, the type of preparation, the mercurial used and its concentra- 

 tion (Table 7-21). As would be expected, there is generally depression of 

 contractile amplitude, rate of beating, and rate of conduction, the last lead- 

 ing to varying degrees of a-v block and dissociation of the atria and ven- 

 tricles. Ventricular standstill often occurs before the atria cease to beat. 

 Tachycardia and fibrillation are frequently seen in animals poisoned acutely 

 with the mercurials, but are not noted in isolated preparations, although 

 occasionally with low concentrations, or initially, some increase in rate and 

 contractile amplitude may be observed. The ventricular dysrhythmias in 

 vivo may be in part the result of altered a-v and ventricular conduction, 

 but in isolated preparations there is little evidence for the appearance of 

 rapidly discharging ectopic foci. Most of these effects are irreversible, or 

 only partially reversible at the lowest concentrations and with short expo- 

 sures, but dimercaprol or cysteine is occasionally able to reverse rather ad- 

 vanced degrees of depression (Ruskin and Johnson, 1949). The selective de- 

 pression of the rat atrial rate is marked; at 0.0013 vaM Hg++ the rate is 

 reduced 35% in 15-20 min while the amplitude is unaffected, and at 0.0025 

 raM the rate may be inhibited 90% and the amplitude some 15% greater 

 than normal (Berman, 1951). Glutathione and dimercaprol effectively pro- 

 tect both the atria and ventricles. 



The development of contracture is not nearly as common with the mer- 

 curials as with iodoacetate, and in fact has been noted only in frog and turtle 

 hearts. Rat atria treated with p-MB are slowly and markedly depressed 



