Our hypothesis is that trauma produces a complex array of physiological and biochemical alterations which are initiated and integrated by neuroendocrine mechanisms for the maintenance of homeostasis - defense of those processes most essential to survival. Probably the most critical process and the common denominator of all of these alterations is the production of energy since all of the physiological defense and repair mechanisms begin to deteriorate when energy resources become depleted. To the extent that shock produces hypoxia in tissues, glucose becomes the sole source of energy production. In concert with our overal hypothesis, we believe that metabolism in the liver adjusts to promote a continuing supply of glucose for energy production during hypovolemic shock. With severe or persisting shock, these adjustments become impaired. The consequent decline in blood glucose is associated with hemoconcentration thought to result from fluid accumulation by skeletal muscle. These studies are directed toward investigation of the mechanisms responsible for the changes in glucose metabolism in liver and muscle obtained from fed and 24-hr fasted rats during the successive stages of hypovolemic shock. The specific objectives of this study are to: a) characterize and correlate the hemodynamic, metabolic and ultrastructural alterations that occur in liver and muscle during persisting shock; b) determine the gluconeogenic capacity, status of energy metabolism and ultrastructure of livers removed from rats during defined stages of shock; c) investigate mechanisms that may inhibit gluconeogenesis during shock including: biochemical factors, oxygen deprivation and hepatic responsiveness to the counter-regulatory hormones; d) determine the relationship between the degree of flow deprivation in """"""""red"""""""" and """"""""white"""""""" muscles to the changes in high energy phosphate levels, metabolic indicators of cellular hypoxia and cell ionic contents; e) investigate the potential rate limiting steps in the glycolytic pathway of muscle; f) correlate these cellular biochemical changes with ultrastructural changes and physiological indices of vascular decompensation, with the goal of evaluating the role of skeletal muscle as a sink for fluid loss from the vascular compartment; g) investigate possible alterations in substrate utilization which may persist in vitro using the isolated soleus and extensor digitorum muscles.
| Pearce, F J; Drucker, W R (1987) Glucose infusion arrests the decompensatory phase of hemorrhagic shock. J Trauma 27:1213-20 |
| Connett, R J; Pearce, F J; Drucker, W R (1986) Scaling of physiological responses: a new approach for hemorrhagic shock. Am J Physiol 250:R951-9 |
| McEnroe, C S; Pearce, F J; Ricotta, J J et al. (1986) Failure of oxygen-free radical scavengers to improve postischemic liver function. J Trauma 26:892-6 |
| Pearce, F J; Connett, R J; Drucker, W R (1985) Phase-related changes in tissue energy reserves during hemorrhagic shock. J Surg Res 39:390-8 |
| Chadwick, C D; Pearce, F J; Drucker, W R (1985) Influences of fasting and water intake on plasma refill during hemorrhagic shock. J Trauma 25:608-14 |
