MORPHOLOGIC RESPONSE OF MYOCARDIUM TO FREEZE-THAW INJURY IN MOUSE STRAINS WITH DYSTROPHIC CARDIAC CALCIFICATION

To investigate the pathogenesis of dystrophic cardiac calcification in mice, we studied myocardial and skeletal muscle (diaphragm) necrosis induced by freeze-thaw injury through the abdominal portion of the dia phragm in DBA/2, C3H/He, and C57BL/6 (control) mice. Two mice from eac h mouse strain were euthanized 6, 12, 24, and 36 h after the initial f reeze-thaw injury; 6 mice from each strain were euthanized 2, 4, 7, 14 , and 28 days after injury, The hearts and diaphragms were studied by light and electron microscopic techniques. Myocardial and diaphragmati c mineralization in response to injury occurred only in DBA/2 and C3H/ He mice and was present as early as 2 days after initial myocyte injur y. Ultrastructurally the mineralized deposits first accumulated in mit ochondria as early as 24 h after injury, with subsequent complete mine ralization of the mitochondria and surrounding sarcoplasm by 48 h. The se results suggest that the pathogenesis of dystrophic cardiac calcifi cation in DBA/2 and C3H/He mice may be related to disturbed myocyte ca lcium metabolism, leading to mitochondrial calcium overload and myocar dial calcification.