Dose-relation of thyroxine-induced changes in myocardial energy stores

Experimental hyperthyroidism was produced in guinea pigs by daily intraperitoneal injection of l-thyroxine (T4) in various doses (0.7, 0.35, 0.175, and 0.07 mg/kg/day) for 7 days. Controls received solvent only. The following metabolites were determined in heart muscle (freeze-stop technique, enzymatic tests): Pi, adenosine tri-, di-, and monophosphates (ATP, ADP, AMP), creatine phosphate (CP), glucose 6-phosphate (G-6-P), fructose diphosphate (FDP), pyruvate, and lactate. Thyroxine induced a dose-related decrease of CP and a corresponding increase of Pi even in the lowest dose used in this study (0.07 mg/kg) and became more pronounced with increased doses. No remarkable changes of adeninenucleotides (ATP, ADP, AMP) were observed. G-6-P and FDP levels were markedly elevated in all dosages. Besides other possible effects (thyroxine-induced activation and induction of enzymes) the dose-related decrease of CP and increase of Pi may be due to the increasing contractility. In the physiological and pathophysiological range of thyroxine doses (T4 less than 20 mug%) high energy phosphates stores are dose-related decreased but not to a critical level. In the toxic range heart failure as a consequence of a deficit of CP may occur.