946 7. MERCURIALS 



to affect the resting potential in either rat or guinea pig atria indicates 

 that no marked changes in intracellular K+ occur during the duration of the 

 experiments, so that appreciable depression of ion pumps or increase in ion 

 permeabilities seem not to be a characteristic of the action on the heart. 

 It is difficult to interpret the cardiac ionic changes noted by Gessler and 

 Bass (1960) in rats poisoned with HgClg, because the electrolyte changes 

 resulting from the renal effects (either polyuria or anuria) probably com- 

 plicate the picture. However, with a dose of HgClg sufficient to produce a 

 long-lasting polyuria there is only a minor fall in the myocardial K+/Na+ 

 ratio (1.78 to 1.60), and, although plasma K+ rises, the tissue/plasma ratio 

 for K+ certainly does not drop very much, although Gessler and Kuner 

 (1960) felt that the qt changes are perhaps correlated with alterations of 

 this ratio. The results on isolated atria support the concept that the major 

 effect is on the ionic flux rates during membrane activation. 



The various regions of the heart respond differently to the mercurials 

 as they do to other inhibitors and drugs. Isolated pig ventricle fibers are 

 not appreciably affected by 0.26 milf p-MB but the Purkinje fibers are 

 more sensitive (Kleinfeld et al, 1964). The action potential magnitude in 

 the ventricle may fall around 10% within 15 min but there is little further 

 change, while the resting potential and action potential duration are not 

 significantly modified. In the Purkinje fibers, on the other hand, the magni- 

 tude of the action potential is rapidly depressed, falling approximately 25% 

 within 10 min, after which another rapid fall occurs between 20 and 30 min. 

 Since the resting potential is unchanged for 20 min, there is initially a 

 marked decrease of the overshoot; the resting potential later falls gradually. 

 The duration of the action potential is surprisingly not altered in contrast 

 to the results in atria. Although no evident explanation for these differences 

 is at hand, it was considered that the greater glycolytic activity of the 

 Purkinje fibers might predispose them to inhibition. We have seen, however, 

 that the glycolytic pathway is probably less sensitive than the cycle to the 

 mercurials. 



(D) Cardiac innervation and responses to acetylcJwline and epinephrine. 

 Salant and Kleitman (1922) noted that Hg++ exerts some vagal blocking 

 action in the cat heart, but Jackson (1926 b) could find no acceleration of 

 the heart and no evidence of vagal block by mersalyl in dogs. Salant and 

 Brodman (1929 a) reinvestigated this question and established that Hg++ 

 first sensitizes the heart to the vagus and later blocks the vagal endings. 

 It is during the first sensitization phase that dysrhythmias are apt to occur, 

 which is reasonable since acetylcholine is profibrillatory as a result of its 

 marked shortening of the action potential duration. Hg++ and p-MB at 

 0.01-0.1 niM antagonize the effects of acetylcholine on the frog heart, the 

 mercurials being allowed to act for 3-40 sec and then washed out (Pohle 

 and Matthias, 1959). It was concluded that the acetylcholine receptors may 



