944 7. MERCURIALS 



• 



but no elevation of resting tension is seen even after 2 hr (Webb and Hollan- 

 der, 1959). It may well be that the mercurials so readily depress membrane 

 functions — pacemaker discharge, conduction, etc. — that the hearts cease 

 beating before they are depleted of ATP. Mendez (1946) noted that frog 

 heart treated with 0.56 mM p-MB stops beating quite soon and before full 

 contracture has developed; however, if the heart is electrically stimulated 

 it can be put into complete rigor. It has been observed many times that the 

 heart stops in diastole in vivo following intravenous injections of the mer- 

 curials. 



(B) Cardiac effects in whole animals. Sudden death during or following 

 the intravenous injection of diuretic mercurials clinically has usually been 

 attributed to ventricular fibrillation. In animals (usually cats and dogs) 

 the mercurials produce the following cardiac effects: initial cardiac depres- 

 sion, disturbances in a-v conduction leading occasionally to a temporary 

 ventricular bradycardia, atrial flutter or fibrillation (rarely), slowing of 

 ventricular conduction, and often ventricular tachycardia before the ter- 

 minal fibrillation (Jackson, 1926 a, b; Salant and Nadler, 1927; Macht, 

 1931 b; DeGraff and Lehman, 1942). The effects may be quite complex and 

 are undoubtedly due to a variety of actions. McCrea and Meek (1929) felt 

 that one of the major actions is a descending stimulation followed by a de- 

 pression of the cardiac conducting tissue. The innervation of the heart 

 probably plays a role in the initiation of the dysrhythmias, since atropini- 

 zation or cutting the vagi in dogs prevents ventricular fibrillation due to 

 mersalyl (Jackson, 1926 a). It is also known that epinephrine potentiates 

 the fibrillatory action of the mercurials. The fall in blood pressure invariably 

 observed during intravenous infusion of the mercurials must induce sym- 

 pathetic activity and a rise in plasma catecholamines. Various salts of Hg++ 

 apparently are not so likely to induce dysrhythmias as the organic mer- 

 curials and are more directly depressant (Salant and Kleitman, 1922). 

 These effects are not dependent on the vagi since they occur after atropini- 

 zation. However, Hg++ can produce conduction disturbances and dysrhyth- 

 mias in dogs, and occasionally ventricular fibrillation (McCrea and Meek, 

 1929). The intravenous lethal dose depends on the mercurial, the species 

 used, and the rate of injection; in most cases it falls between 10 and 50 mg 

 Hg/kg for the common diuretic mercurials (DeGraff and Lehman, 1942; 

 Chapman and Shaffer, 1947; Lehman et al., 1950; Farah et al., 1951). Inor- 

 ganic Hg++ is somewhat more toxic, the lethal dose usually being around 

 one third to one half that for the organic mercurials. The toxicity of Hg++ 

 is dependent on the blood pH, being least between 7.4 and 7.6, and increas- 

 ing on either side, especially between 7.14 and 7.35 (Salant and Nadler, 

 1927). Since comparable experiments have not been run on isolated 

 hearts, it is impossible to understand the mechanism for this sensitive pH 

 dependence; it is difficult to accept that a direct effect of pH could 



