Biochemical and ultrastructural changes in rat liver plasma membranes after temporary ischemia

In this study we have attempted to correlate reversible and irreversible cell damage induced by in vivo or in vitro ischemia with characteristics of the plasma membranes of liver parenchymal cells, as detected biochemically and ultrastructurally. The effects of in vivo or in vitro ischemia appeared to be similar. It was virtually impossible to isolate a substantial membrane fraction from ischemic livers, probably because of changes in the physical properties of the membranes by ischemia. The isolated membranes of ischemic liver cells show ultrastructural changes including the occurrence of many vesicular profiles and alterations in junctional complexes expressed by extended and smudged electron densities along the lateral surfaces. The microvilli of the bile canaliculi disappeared after only 15 min ischemia and cytoplasmic densities associated with junctional complexes also appeared extended and smudged. These changes correspond with the alterations observed in ischemic isolated membranes. After 30 min in vivo ischemia the activity of 5'-mononucleotidase used as a marker enzyme for plasma membranes, decreased by 75%, whereas the activity of thymidine 5'-phosphodiesterase was reduced only slightly. The changes in these enzyme activities were more prominent after in vitro ischemia than after in vivo. The morphological and biochemical changes observed in rat hepatocyte plasma membrane during the early stage of injury have no value in predicting the occurrence of necrosis in a later phase of the process since profound changes occur in plasma membrane properties after even short periods of ischemia (i.e. during the reversible stage).