Malonate and fluoride effects on metabolism and contraction of electrically stimulated heart strips

¹ Department of Pharmacology, School of Medicine, University of Southern California, Los Angeles, California

The effect of malonate and fluoride on the oxidation of C¹⁴-labeled substrates by electrically stimulated rat heart strips was investigated in an apparatus which permitted simultaneous recording of oxygen consumption and contractile activity. Malonate stimulated the force of contraction when glucose was the substrate, but not in the presence of pyruvate. Malonate had no significant effect on the rate of oxidation of glucose-1-C¹⁴, glucose-6-C¹⁴ or pyruvate-2-C¹⁴, indicating that its effect on contraction was not related to a) stimulation of glucose metabolism, b) inhibition of the Kreb's cycle, or c) stimulation of the phosphogluconate pathway. Malonate-2-C¹⁴ was oxidized by the ventricle strips, and the possibility exists that utilization of malonate as a substrate may account, at least in part, for its stimulation of contraction. The stimulation of contraction by fluoride was accompanied by significant alterations in metabolism. The oxidation of glucose and acetate was inhibited, whereas pyruvate oxidation was stimulated; these findings were interpreted in terms of known actions of fluoride on enzyme systems.