Effects of amiodarone on 5'-deiodination of thyroxine to tri-iodothyronine in rat myocardium.

The present work studied the effects of amiodarone (AMD) and iopanoic acid (IA) on the conversion of thyroxine (T4) to tri-iodothyronine (T3) by rat myocardium. In vivo: male Wistar rats weighing 200-250 g were injected i.p. with AMD (2.5 mg/100 g body weight per day for 12 days) or IA (5 mg/100 g body weight every 12 h for 72 h). Hearts were then removed and processed as in the in-vitro studies. In vitro: hearts were homogenized in Krebs-Ringer phosphate buffer (pH 7.4) and AMD (0.1 mmol/l) or IA (10 mmol/l) plus dithiothreitol (8 mmol/l) and 0.01 microCi [125I]T4 or [125I]T3 were added. After incubation for 2 h at 37 degrees C, radioactive compounds were identified by paper chromatography. Both AMD and IA given in vivo blocked T4 and T3 conversion significantly (P less than 0.005). When added in vitro, AMD failed to inhibit T4 deiodination to T3 whereas IA induced a significant (P less than 0.005) decrease in T3 generation. Deiodination of [125I]T3 by heart homogenates was not altered by AMD or IA. While the expected increase in circulating T4 (P less than 0.001) and decrease in T3 (P less than 0.001) did occur after AMD or IA treatment, plasma TSH in AMD-treated rats was decreased (P less than 0.001), while in IA-treated animals it was increased (P less than 0.001), thus indicating that AMD did not inhibit pituitary type-II 5'-monodeiodinase.(ABSTRACT TRUNCATED AT 250 WORDS)