Intracellular monitoring of experimental respiratory failure

The view that intracellular changes during oxygen depletion are the primary cause of abnormal function and altered physiology was originally proposed by Paul Bert. From that time it remains a basic assumption that hypoxia in intact animals produces alterations of cell and organ function, and that by measuring the intensity of these disturbances or the intensity of the functional impairment produced by these disturbances, a clearer understanding of the impact and consequences of oxygen depletion should emerge. At present, intracellular changes are inferred from the measurement of extracellular signals such as blood pressure, arterial oxygen tension and pH, or hemoglobin saturation, which provide mean values of changes occurring over the entire body. However, cells and organs in different parts of the body respond differently to a given degree of hypoxia or ischemia, and measurements of extracellular variables cannot provide precise information about abnormalities in any specific organ. Extracellular variables also do not reflect adaptive responses of a specific organ such as autoregulation of its blood flow and the ability to alter energy demand in response to changes in energy production. Other factors include differences in metabolic rates and dependence upon oxidative and glycolytic reactions, cell heterogeneities within a tissue organ, redistribution of blood flow to various organs during hypoxia, or other insults, and other, yet unknown, cell-specific changes that result in a range of survival capabilities among organs. These considerations suggest the importance of direct monitoring of intracellular changes produced by cardiovascular or respiratory diseases. However, until recently, direct measurement was confined to the laboratory. In recent years, new technologies have developed that allow noninvasive measurements of intracellular events. During the past three years, a collaborative effort was pursued that investigated intracellular monitoring using two experimental models of oxygen depletion, arterial hypoxemia, and blood loss hypotension. The perspective that emerged from these studies raised the possibility that these methods, several of which are currently being employed to study and monitor hypoxia in human neonates, may be applied generally to the evaluation of human patients with hypoxic or ischemic disorders.