Inotropic Effects of Purines and Pyrimidines on the Isolated Heart

Abstract

Hypoxanthine, guanine, thymine, and uracil were found to be positively inotropic for failing left ventricle preparations of the dog heart. Inosine, guanosine, thymidine, uridine, and their corresponding bases were found to be positively inotropic for failing rabbit hearts perfused with an artificial medium. Adenosine and cytidine and their corresponding bases were found to be negatively inotropic. Inosine, guanosine, uridine, and their constituent bases, and thymine were found to be positively inotropic for nonfailing rabbit hearts perfused with an artificial medium. Compounds that had hydroxyl groups in addition to one in the six position (xanthine, uric acid, 5-hydroxyuridine, barbituric acid and alloxan) had no consistently positive inotropic effects. The methylated purine, caffeine, was always positively inotropic. Compounds containing other substituents in the four or six position (6-mercaptopurine; 6-chloropurine; 2,4,6-trichloropyrimidine; 4-carboxypyrimidine) had no consistently positive inotropie effects. The carboxy derivative of uracil, orotic acid, was always a positive inotrope. Parent ring compounds such as purine, pyridine, and benzene had no consistent inotropic effects, while pyrimidine was always positively inotropic. Four consistently negative inotropic substances were found among all these compounds: xanthine, alloxan, 6-chloropurine, and 4-carboxypyrimidine. It was concluded that the constituent bases of naturally occurring nucleosides have cardiac effects similar to those of the nucleosides and that their inotropic effects are characteristic in both failing and nonfailing hearts.