THE ACTIONS OF METHYL FLUOROACETATE ON THE PAPILLARY MUSCLE OF THE CAT WITH COMPARATIVE EXPERIMENTS ON THE ACTIONS OF METHYL CHLOROACETATE

¹ Department of Pharmacology, Cornell University Medical College, New York 21, N. Y.
² Kurume Medical College, Fukuoka-Ken, Japan

The results of the present experiments describe the toxic effects of MFA and MClA on the cat's papillary muscle in vitro. The principal action of these substances is to cause a deterioration of the contractile mechanism of the myocardium. This effect can be opposed to some extent by pyruvate, and this fact is shown to provide support for the concept of competitive antagonism between MFA and pyruvate. The conducting system of the papillary muscle is relatively insensitive to the action of either MFA or MClA. On the other hand, those electrical events associated with the restorative processes of the fiber are profoundly altered as a result of fluoroacetate poisoning. These effects on contraction and repolarization processes develop with comparative slowness after the exposure of the muscle to MFA or MClA. In contrast, the stronger oxidative poisons, like simple anoxia or cyanide, disrupt both mechanical and electrical events rapidly and simultaneously. It is suggested, therefore, that the toxic actions of MFA, and probably those of MClA arise from an inhibition of pyruvate metabolism and in essence are equivalent to the effects of substrate depletion. It is concluded that the development of ominous arrhythmias and conduction disturbances, in the heart of the intact cat poisoned with MFA, occur as a consequence of a primary disintegration of the contractile mechanism. Finally, the specific accumulation of citrate, demonstrable in the tissues of an animal poisoned with MFA, can be shown for the poisoned papillary muscle in vitro. In this regard, MClA is unlike MFA in that citrate cumulation does not occur, although the toxic effect on the papillary is similar to that of MFA. On the basis of this finding it is suggested that a causal relationship between citrate cumulation and the characteristic pharmacologic effects of MFA is uncertain.