Autophagic response to sublethal injury in cardiac myocytes

Fetal mouse hearts maintained in oxygenated organ culture media continue to beat for a period of weeks. Study of the ultrastructure of the myocytes after the first day in culture revealed that most of the cells were normal, however an occasional cell had autophagic vacuoles within the cytoplasm which contained degenerating organelles indicating that focal cytoplasmic injury had occurred. Deprivation of oxygen and glucose for a period of time followed by resupply resulted in increased numbers of autophagic vacuoles. In this study, fetal mouse hearts were maintained from 1 to 4 h in glucose-free media in an atmosphere of 95% N-5% CO 2 after which resupply of O 2 and glucose was maintained for as long as 24 h. Many cells recovered without apparent residual injury while others contained autophagic vacuoles in an otherwise normal cytoplasm. The contents of the vacuoles ranged from those in which organelles were readily identified to those characteristic of residual bodies. Mitochondria, glycogen and tubular structures were seen most frequently in the vacuoles but occasionally myofilaments were identified. It is suggested that focal cytoplasmic injury which occurred during oxygen and glucose deprivation stimulates the formation of membrane to enclose the irreversibly damaged components permitting localized lysosomal digestion without causing further injury to the cell. The fetal mouse heart organ culture provides an excellent model for studying the sequential autophagic changes which occur in response to sublethal injury.