Response of the Isolated Perfused Hepatic Parenchyma to Hypoxia

Abstract

Isolated perfused livers from male rats were subjected to hypoxia by ligation of lobes and by perfusion with hypoxic blood respectively. Specimens for study under the electron microscope were taken before and at the conclusion of periods of hypoxia of both types and during the recovery phase lasting 2 hours. The rate of flow of bile was reduced by hypoxia[long dash]more after 1 to 2 hours than after 30 minutes. Recovery after restoration of access to oxygen was only transient. Differences were found in the appearance of the hepatic parenchyma when the methods of inducing hypoxia were compared. In ligated specimens, the biliary canaliculi were closed; whereas more and larger vacuoles were found, the amount of glycogen was less and the cells were more eroded (even though the plasma membrane was not ruptured more frequently) in preparations perfused anaerobically. After 30 minutes the electron microscopy of the liver showed many changes after anaerobic perfusion or ligation for more than 1 hour in contrast to the focal vacuolization of the cytoplasm which was the only change detected by the light microscope after anaerobic perfusion for similar periods of time. Changes in fine structure included nuclear clumping and margination, loss of mitochondrial granules, alteration in distribution and greater decrease in the amount of glycogen than accounted for by fasting in situ, and cellular swelling. Other changes were flattening and disruption of the plasma membrane, vesiculation and disorganization of the endoplasmic reticulum and vacuolization of the cytoplasm. The cytoplasmic vacuoles contained acid phosphatase, an enzyme normally associated only with lysosomes, as well as isolated portions of cellular organelles. It is postulated that 3 cellular changes[long dash]disorganization of endoplasmic reticulum, disruption and flattening of cellular membrane and vacuolization of cytoplasm[long dash]probably contribute to the loss of viability of the cell. Biochemical events correlated with these morphologic changes, although complex, should be followed more easily when the sequence of cellular alterations are used to design experiments for the purpose of elucidating cellular mechanisms of importance in shock or the clinical entities in which hypoxia and/or ischemia are features.