Pathogenesis of heart myofibril lesion in experimental vitamin D-induced cardionecrosis.

Multifocal cardionecrosis has been produced in rats by treatment with 3 x 100,000 iu vitamin D3 (calciol). The effects of hypervitaminosis D on rat heart myofibril structure and total protease activity was investigated. Proteolytic enzyme activity of heart muscle homogenate was determined in two independent ways, and was approximately two times higher in the necrotic heart homogenate than in the control rat heart. Electron microscopic examinations showed structural derangements. Myofibrils isolated from necrotic heart exhibited significant changes of ultrastructure in the region of Z-line and I-band. Myofibril enzyme activity (Mg(2+)-ATPase) measurements demonstrated functional deficits as well. Under different conditions of myofibril isolation, it was shown that both ultrastructural and enzymatic lesions appear to be mediated by calcium-activated proteolytic enzymes operating in situ. Our results indicate that the increased proteolytic activity caused by vitamin D treatment leads to the in situ damage of proteins of the heart contractile system.