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Effects of Grisorixin on the Distribution of Thallium-201 and on the Oxidative Metabolism in Cultured Myocardial Cells

Divisions of Nuclear Medicine and Nephrology, Harbor-UCLA Medical Center, Torrance, California
Department of Pharmacology, U195 INSERM, University of Clermont 1, Clermont-Ferrand, France
Allan Hancock Foundation, University of Southern California, Los Angeles, California

Correspondence: For reprints contact: J. C. Maublant, MD, Nuclear Medicine, Centre Jean Perrin, 63011 Clermont-Ferrand, France.

ABSTRACT

Previous experiments in the dog and guinea-pig have shown that grisorixin, a monocarboxylic ionophore, can significantly increase the coronary blood flow and the myocardial uptake of ²⁰¹Tl, as well as have a stimulant effect on the heart. In this study, cultures of myocardial cells were used in order to isolate the cells from the vascular and extracardiac influences so that any ionophorous effect on ²⁰¹Tl could be evidenced. The effects of grisorixin on the oxidative metabolism were simultaneously studied. The technique described by Harary was used to prepare the cultures. The activity of the ¹⁴CCO₂ produced by oxidation of [¹⁴C]glucose and [¹⁴C]octanoate added to the medium of culture and the intra/extracellular ratio of ²⁰¹Tl concentrations (Tl i/e) were measured. In the controls (n = 8), the Tl i/e was 40 ± 10 while it was 17 ± 6 (p < 0.05) in the cells that received ²⁰¹Tl and grisorixin at the same time (n = 4), and 19 ± 5 (p < 0.05) in the flasks where ²⁰¹Tl was injected after grisorixin (n = 7). A significant decrease of the [¹⁴C]octanoate oxidation was found in the flasks treated with grisorixin (n = 4, –50 ± 16%, p < 0.01) while the [¹⁴C]glucose oxidation was not significantly lowered (n = 3; –11 ± 12%). The conclusion is that grisorixin decreases both the intracellular concentration of ²⁰¹Tl and the fatty-acids oxidation in cultured myocardial cells. The beneficial effects previously observed in vivo were probably the consequence of the strong coronary dilatation and of an indirect stimulation.