ABNORMALITIES OF CONTRACTILE STRUCTURES IN VIABLE MYOCYTES OF THE FAILING HEART

We examined the incidence and severity of abnormalities of contractile structures of residual viable cardiomyocytes in the left ventricular free wall, septum and right ventricular free wall of 0 dogs with chronic heart failure produced by multiple intracoronary microembolizations and in septal biopsies of 13 patients with chronic heart failure. The abnormalities were evaluated by transmission electron microscopy and classified as either (i) type-1, defined as complete interruption of myoribrils; (ii) type-2, defined as disconnection of end-sarcomeres from the intercalated disc, or (iii) type-3, sarcomere abnormalities defined as Z-bands irregularities and/or focal myofilament disarray. In the left ventricular free wall of dogs, type-1 abnormalities were present in 33 +/- 8% of myocytes, type-2 in 26 +/- 8%, and type-3 in 63 +/- 9%. The incidence of a type-3 abnormality but not type-1 or type-2 was greater in the left ventricular wall compared with the septum and right ventricular wall (P < 0.05). Among abnormal myocytes, 29 +/- 3% of myofibrils were interrupted, 18 +/- 4% of end-sarcomeres were disconnected from the intercalated disc and 12 +/- 2% of sarcomeres were abnormal. The severity of a type-1 but not type-2 or type-3 abnormalities was greater in the left ventricular wall compared with the septum and right ventricular wall. A similarly high incidence of abnormalities was observed in septal myocytes of patients. The results indicate that abnormalities of contractile structures are common among viable myocytes of the failing heart. The incidence of these abnormalities is sufficiently high to warrant serious consideration of their potential role in the progression of left ventricular dysfunction that characterizes the heart failure state.