The Relative Roles of Oxygen Concentration and Delivery in Maintaining Cell Function and Viability.

This report is a comprehensive summary of 3 years work directed at the investigation of the relative roles of oxygen and substrate in maintenance of normal cell function. The brain was selected as the initial organ of study due primarily to the fact that CNS dysfunction is a leading cause of death secondary to severe trauma and hemorrhage. A clinically relevant model combining hypotension and hypoxia had been developed in the rat by the investigators and has been used throughout this study. In the final series of experiments, attention was directed to the effects of glucagon on hepatic cellular energetics during low flow states. The framework within which these studies were carried out was based on a broad hypothesis of cellular alterations in shock and trauma. This hypothesis states that with shock and diminished tissue perfusion, there seems to be an initial alteration in the cell membrane with changes in its capability to properly perform. Na probably enters the cell, NA plus K ATP-ase is activated, ATP is used and the mitochondria are stimulated. Cyclic AMP decreases which may result in alterations in insulin, glucagon, catacholamines, and corticosteroids. Further Na enters the cell the cell swells, with mitochondrial swelling as well. Metabolic capability decreases as these alterations in cation content and hydration of the cell and intra-cellular organelles occur.