CELLULAR AND TISSUE FUNCTION 



215 



of Ca+"'". However, there are some reservations in accepting this explanation 

 completely. In the first place, Ca++ stimulates atrial contractility and would 

 be expected to counteract most depressants in a nonspecific manner. In 

 the second place, reducing the Ca++ from 1.22 mM to 0.91 mM does not 

 alter the contractility, although further reduction to 0.61 mM depresses 

 43%. Malonate at 15 mM would reduce the Ca++ from 1.22 mM to 0.82 mM 

 and a small contractile depression may result from this. The total Ca++ in 

 Locke solution is 2.16 mM and 20 mM malonate would reduce the free 

 Ca++ to 1.31 mM, which alone could not produce the 90% depression seen 

 by Venturi and Schoepke. In the third place, monocarboxylate ions, such 

 as acetate, lactate, and pyruvate, at 20 mM depress the contractile am- 

 plitude 40-45% and these do not deplete the Ca++. 



The modifications in the electrocardiogram following intravenous injec- 

 tions of malonate into turtles were studied by Lenzi and Caniggia (1953). 

 At a dose of 4.4 millimoles/kg malonate the following occurred: brady- 

 cardia, slowing of the a-v conduction, a tendency for the shortening of 

 repolarization and electric systoles, with eventually a total a-v block 

 and a prolongation of the depolarization time (see accompanying tabula- 

 tion). Pacemaker and conduction depression are thus evident, and it is 



quite possible that similar changes would be observed in mammals, con- 

 sidering the general behavior of the heart in cats and rabbits treated with 

 malonate (Forssman and Lindsten, 1946). The electrocardiogram from the 

 embryonic chick heart is not altered by 4 mM malonate (Boucek and Paff, 

 1961). 



In contrast to the depressant effects of malonate on the whole heart and 

 isolated atria, the rat ventricle strip is usually strongly stimulated, as first 

 noticed by Masuoka et al. (1952). Substrate-depleted and hypodynamic strips 

 recover to almost the initial contractile amplitude upon addition of 10 mM 

 malonate at pH 6.2 (which was used to facilitate penetration of the mal- 

 onate), and simultaneously the stimulatory action of succinate is blocked. 

 The ability of glucose to induce recovery is augmented by malonate, and 

 that of pyruvate is slightly reduced (Berman and Saunders, 1955). This 

 interesting positive inotropic action was analyzed in detail because it was 



