ALTERED NUCLEUS CYTOPLASM RELATIONSHIP AND DEGENERATIVE STRUCTURAL-CHANGES IN HUMAN DILATED CARDIOMYOPATHY

We investigated systematically the structure of the myocardium obtaine d from patients with dilated cardiomyopathy undergoing transplantation because of intractable heart failure. Hearts were explanted at the ti me of surgery from 12 patients (10 men and 2 women, aged 31-57 years, ejection fraction < 20%) and numerous samples were taken for light and electron microscopy. Biopsies from the left ventricle of 8 patients d uring operations for atrial septal defect served as control tissue. Th e most obvious qualitative findings were focal hypertrophy and atrophy of myocytes, enlargement and bizarre shape of nuclei, lack of contrac tile material and occurrence of numerous small mitochondria. On a quan titative level, the nuclear density was reduced (18 %, p < 0.05) but t he nuclear profile area was significantly increased (85 %, p < 0.001). Thus the nucleus/cytoplasm relationship was altered. The volume densi ty of the contractile filaments was decreased (25 %, p < 0.001), but t he mitochondrial volume density was unchanged. There was an increase i n cell width (39 %, p < 0.01) and of the connective tissue content (= fibrosis) (112 %, p < 0. 001). It is suggested that the nuclear abnorm alities may be the primary event in the pathogenesis of dilated cardio myopathy. These may then lead to a reduced transcriptional rate which most probably is the cause of the lack of myofilaments and other degen erative changes. The deterioration of the structural quality of the hy pertrophied myocytes results finally in atrophy and fibrosis and may b e the structural correlate of functional disturbances in dilated cardi omyopathy.