Parathyroid ablation in dystrophic hamsters. Effects on Ca content and histology of heart, diaphragm, and rectus femoris.

Cumulative evidence indicates that there is an increased accumulation of calcium in dystrophic muscle and that this may have a pathophysiological role in the progression of the dystrophic process. The accumulation may be related to a defect of the plasma membrane. Because parathyroid hormone (PTH) stimulates calcium influx into the cytosol, the chronic effects of surgical ablation of the parathyroid glands on muscle Ca, Mg, protein synthesis, and histology, as well as plasma creatine phosphokinase (CPK), Ca, and Mg, were studied in normal and dystrophic (BIO 14.6) hamsters. Thyroparathyroidectomized (TPTX) hamsters receiving replacement doses of l-thyroxine were killed at age 90 d, 55 d after TPTX. In intact dystrophic hamsters, the Ca content in the heart was 20 times higher than in normal animals and was reduced by half in TPTX dystrophic hamsters. Similar results were observed in diaphragm and rectus femoris. No abnormalities in Mg content were observed in intact or TPTX dystrophic hamsters. Ether-extractable fat of the heart and diaphragm was reduced in dystrophic hamsters and was not modified by TPTX. Protein synthesis was enhanced in the diaphragm of dystrophic hamsters but was not changed by TPTX. The concentration of CPK in plasma was elevated in dystrophic hamsters and fell significantly after TPTX. In the latter animals, microscopic examination of the heart showed lesser signs of dystrophy, particularly in the degree of fibrosis. To determine the degree of dystrophy at the age when TPTX was performed, identical analyses were made in 35-d-old hamsters. Definitive histological signs of dystrophy were observed, and although the Ca content in heart, diaphragm, and rectus femoris was elevated, the values were lower than in 90-d-old intact and TPTX dystrophic hamsters. This indicates that chronic TPTX in dystrophic hamsters reduces, but does not arrest, the dystrophic process. In normal hamsters, a 50% reduction in plasma Ca concentration was observed 6 h after TPTX; 55 d after TPTX, however, plasma Ca was within normal limits in both normal and dystrophic hamsters. No parathyroid tissue was observed in serial sections of the trachea and adjacent tissues in TPTX animals. This suggests that in chronically TPTX hamsters fed a standard laboratory diet, plasma Ca can be maintained by mechanisms independent of parathyroid function. THE DATA INDICATE THAT IN DYSTROPHIC HAMSTERS TPTX CAUSES A MARKED REDUCTION IN: (a) muscle Ca accumulation, (b) levels of plasma CPK and, (c) intensity of histological changes in the heart. These changes were independent of the levels of plasma Ca and were not observed in normal hamsters. We conclude that PTH accentuates the dystrophic process, probably by enhancing the already increased Ca flux into muscle (apparently caused by defective sarcolemma). We postulate that normal secretion of PTH may have a deleterious effect in congenital or acquired conditions associated with altered plasma membranes.