EFFECTS ON TISSUE FUNCTIONS 945 



alter 2- or 3-fold the sensitivity of the heart to the Hg++ ion, and it is 

 more likely that secondary changes due to the alteration of the pH are 

 responsible. 



The electrocardiographic changes in dogs are similar for all the diuretic 

 mercurials tested and for HgCl,, and are primarily the result of conduction 

 disturbances. They may be summarized briefly as follows: depression and 

 change of configuration of the st segment, increase in height of the t wave, 

 widening and notching of the qrs complex, widening of the p wave, and 

 increase of the p-r interval (McCrea and Meek, 1929; Farah et al., 1951). 

 In the rat there is an initial flattening of the t wave, and eventually the 

 p wave may disappear (Gessler and Kuner. 1960). Most of these changes 

 are, of course, simply due to the slowing of conduction throughout the 

 myocardium. The t wave changes are different from those seen with most 

 metabolic inhibitors and are perhaps related more to a membrane effect 

 than a metabolic disturbance. It is interesting that p-MB acts differently 

 than the mercurial diuretics in that no qrs changes are seen, even at doses 

 2-3 times the lethal doses of the other mercurials, and death is not due to 

 fibrillation but to ventricular asystole (Farah et al., 1951). The lethal dose 

 of p-MB is also about 4 times as great as for the other mercurials. 



(C) Transmembrane potentials and ionic shifts. The membrane charac- 

 teristics of rat atria are changed markedly by 0.05 mM p-MB, although 

 the rate of action is rather slow (this is probably not due to slow penetra- 

 tion into the atria since the potentials are recorded from cells at the sur- 

 face) (Webb and Hollander, 1959). During the first 20-30 minutes there is 

 no significant alteration of the contractile behavior, but there is a progres- 

 sive reduction in the magnitude of the action potential, an acceleration of 

 the repolarization rate, and a slowing of conduction. It is possible that these 

 early effects arise from selective action on the cell membranes. During the 

 next hour these changes continue but, in addition, contraction becomes im- 

 paired. At 1 hr the changes may be summarized as follows: no significant 

 change in resting potential ( + 2.1%), a severe depression of the action 

 potential magnitude ( — 29%), a faster repolarization ( + 51%) leading to 

 a shorter action potential (—60%), a decrease of the developed tension 

 ( — 48%), a slowing of conduction (—38%), and a prolongation of the 

 latent period (+61%). Even during this later period it appears that the 

 contractile depression is due mainly to the shortening of the action potential, 

 and to some extent to its reduced magnitude, and there is little evidence 

 for direct effects on the contractile systems. It may well be that p-MB 

 penetrates into the cells rather poorly and that some of the other mercurials 

 would not have so selective an action on the membrane. Stein et al. (1960) 

 reported that mersalyl (0.2 mM) causes a faster repolarization and contrac- 

 tile depression in guinea pig atria, but no changes in either the resting or 

 action potential magnitudes were observed. The failure of the mercurials 



