Effect of phenformin on the metabolism of glucose, pyruvate and acetate in guinea-pig heart.

In the isolated perfused heart of the guinea-pig, phenformin could be shown to have a characteristic effect on cardiac performance and metabolism. In the working heart, phenformin (1 mmol1/1) decreased dp/dt and increased the end diatolic pressure; this reduced heart performance could not be explained by changes in the content of energy-rich compounds. Furthermore, phenformin increased lactate production in hearts perfused with glucose as substrate and inhibited the utilisation of pyruvate, but not of acetate. The activity of the purified pyruvate dehydrogenase complex was not influenced by phenformin, but the active form of the pyruvate dehydrogenase complex (PDHa) was diminished. This effect may be explained by an inhibition of the pyruvate dehydrogenase phosphatase. An inhibition of pyruvate dehydrogenase and, coincidently, of oxygen consumption might contribute to the development of lactic acidoses and, particularly, might be deleterious for the heart.