ACTION OF NARCOTICS AND LOCAL ANESTHETICS ON THE RESPIRATION OF HEART MUSCLE

¹ Department of Pharmacology, Harvard Medical School, Boston

1. In concentrations producing a moderately severe failure of the isolated dog heart the narcotics pentobarbital, chiorobutanol, paraldehyde, and propazone markedly reduce the respiration of dog and guinea pig heart muscle slices, while the local anesthetics cocaine, procaine, and tetracaine have no effect even in several times the corresponding concentrations.

2. The increase in the respiration of guinea pig heart slices caused by pyruvate is nearly completely prevented by pentobarbital and chlorobutanol in concentrations which produce only a moderately strong inhibition of respiration in the presence of glucose or acetate or in the absence of added substrate. The R. Q. of guinea pig heart slices incubated in pyruvate is 1.2 and is not changed by pentobarbital. The endogenous R. Q. and the R. Q. in the presence of glucose remain likewise unchanged.

3. From the respiratory data it appears that oxidation of succinate to fumarate in guinea pig heart slices is not inhibited by pentobarbital and chlorobutanol and proceeds at a rapid rate. However, the increase in respiration ascribed to the further oxidation of succinate is strongly inhibited. In the presence of sufficiently large concentrations of succinate and narcotic, carbon dioxide production ceases and almost the whole oxygen uptake can be accounted for by the oxidation of all the succinate to fumarate.

4. None of the above named narcotics and local anesthetics inhibits the anaerobic glycolysis of dog and guinea pig heart slices in concentrations producing a moderately severe failure of the isolated dog heart.

5. The inhibitory aetion of the narcotics on the respiration of the myocardium is not considered to be the cause of their depressant action on the functional activity of the heart.