[The effect of mildronate on disorders of the cardiac contractile function in rats caused by an excess of free fatty acids and ischemia]. / Vliianie mildronata na narusheniia sokratitel'noi funktsii serdtsa krys, vyzyvaemye izbytkom svobodnykh zhirnykh kislot i ishemiei.

Oral administration of mildronate, 3-(2,2,2-trimethylhydrazine)propionate, an inhibitor of carnitine-dependent metabolism, in a dose of 50-100 mg/kg for 10 days promoted a rapid restoration of contractility of Langendorf perfused rat heart preparations during postischemic perfusion and protected the rat hearts against inhibition of contractile function resulting from continuous perfusion with palmitic acid. Mildronate inhibits gamma-butyrobetaine hydroxylase, depresses carnitine biosynthesis and reduces carnitine-dependent fatty acid metabolism. The cardioprotective effect of mildronate is particularly manifest upon continuous administration.

[Effect of DL-carnitine and gamma-butyrobetaine hydroxylase inhibitor 3-(2,2,2-trimethylhydrazinium) propionate on isoproterenol-induced changes in the metabolism of the rat myocardium]. / Vliianie DL-karnitina i ingibitora gamma-butirobetaingidroksilazy 3-(2,2,2-trimetilgidrazinii) propionata (TGP) na vyzyvaemye isoproterenolom izmeneniia v metabolizme miokarda krys.

3-(2,2,2-trimethyl hydrazinium) propionate (THP) is known as an inhibitor of gamma-butyrobetaine hydroxylase in rat liver tissue. At the same time, THP, administered per os at a dose of 100 mg/kg within 10 days, prevented the isoproterenol-induced (subcutaneously, 50 mg/kg) acylcarnitine accumulation. This effect of THP, accompanied by a distinct decrease of free carnitine in rat myocardium, occurred due to inhibition of carnitine biosynthesis from gamma-butyrobetaine. THP protected the myocardium energetics against isoproterenol action as the drug prevented the acylcarnitine accumulation. Although D,L-carnitine (200 mg/kg, per os, 10 days) inhibited also the isoproterenol-stimulated acylcarnitine accumulation in rat myocardium and fatty acids of blood serum, in did not exhibit any favourable effect on myocardium bioenergetics. Inefficiency of D,L-carnitine as cardioprotective drug may be a result of intensification of fatty acids metabolism occurring simultaneously with isoproterenol-mediated myocardium ischemia. Use of inhibitors of carnitine-dependent oxidation of fatty acids oxidation (as exemplified by THP) in order to correct myocardium metabolism is of importance especially in relation to impairing effects caused by catecholamines.