Heart Mitochondrial Function in Acute and in Chronic Hyperthyroidism in Rats

The effects of acute versus chronic hyperthyroidism on rat heart mitochondria were explored. Acute, severe hyperthyroidism with an 18% loss of body weight was induced by injecting subcutaneously 10 μg/100g/day of triiodothyronine for 6 to 14 days, and chronic, anabolic, moderate hyperthyroidism was induced by placing triiodothyronine in the drinking water at a dose of 25 or 50 μg/100 ml for 15 to 60 days. Mitochondrial function was assessed polarographically using α-ketoglutarate as the oxidizing substrate, and mitochondrial structure was assessed indirectly from changes in rates of swelling in decimolar alkaline salt solutions in vitro. The P-O ratios of heart mitochondria isolated with Nagarse incubation from both types of hyperthyroid rats decreased slightly (15%) but significantly (P = 0.05). Simple dilution of the hyperthyroid mitochondrial suspensions effected a 75% increase in the P-O ratio of the acutely treated rats but only a 19% increase in that of the chronically treated rats. Significantly increased susceptibility to swelling in vitro was exhibited only by the mitochondria of the chronically triiodothyronine-treated rats. On the other hand, only those of the acutely treated rats showed significant increases in the activity of Mg2+-stimulated mitochondrial ATPase. These data suggest that the mechanisms whereby excess thyroid hormone in vivo affects the function and structure of isolated rat heart mitochondria vary with the mode of induction and the duration of the hyperthyroid state.