ObjectiveTo determine the effect of trauma on arginase, an arginine-metabolizing enzyme, in cells of the immune system in humans. Summary Background DataArginase, classically considered an enzyme exclusive to the liver, is now known to exist in cells of the immune system. Arginase expression is induced in these cells by cytokines interleukin (IL) 4, IL-10, and transforming growth factor beta, corresponding to a T-helper 2 cytokine profile. In contrast, nitric oxide synthase expression is induced by IL-1, tumor necrosis factor, and gamma interferon, a T-helper 1 cytokine profile. Trauma is associated with a decrease in the production of nitric oxide metabolites and a state of immunosuppression characterized by an increase in the production of IL-4, IL-10, and transforming growth factor beta. This study tests the hypothesis that trauma increases arginase activity and expression in cells of the immune system. MethodsSeventeen severely traumatized patients were prospectively followed up in the intensive care unit for 7 days. Twenty volunteers served as controls. Peripheral mononuclear cells were isolated and assayed for arginase activity and expression, and plasma was collected for evaluation of levels of arginine, citrulline, ornithine, nitrogen oxides, and IL-10.

The dose-response relation between plasma glucose and brain lactate and the relation of these parameters to intracellular pH during severe cerebral ischemia have not been well characterized over a wide range of plasma glucose levels. Experiments to delineate these relations in the gerbil model of global ischemia were performed by using phosphorus-31 nuclear magnetic resonance spectroscopy to measure intracellular pH and a new method to measure brain lactate. Ischemia increased final brain lactate linearly 4 /tmol/g for every 100 mg/dl increase in plasma glucose up to 650 mg/dl (p=0.0001, ^=0.9); beyond 650 mg/dl, saturation of the glucose transport-glycolysis system occurred. Plasma glucose correlated better with ischemic intracellular pH than did brain lactate. However, when brain lactate levels are compared with intracellular pH during ischemia, the relation may be threshold rather than linear. A narrow transition zone, during which ischemic intracellular pH decreased precipitously with increasing brain lactate, was observed between 17 and 22 fimoUg; below 17 fimollg, intracellular pH remained stable at 6.8-6.9, whereas above 22 /imol/g, intracellular pH decreased maximally to about 62. The marked decrease in intracellular pH that occurs when brain lactate surpasses 17 /unol/g suggests that this sudden drop in intracellular pH may account for the "lactate threshold" for increased cerebral ischemic damage. (Stroke 1990^21:936-942) S ince the observation by Myers and Yamaguchi 1 that glucose infusion increased brain injury from cardiac arrest, the ability of hyperglycemia to enhance cerebral ischemic damage after transient ischemia has become well accepted. "5 The increased ischemic brain damage in the presence of hyperglycemia is believed to be related to increased production of lactate and to the accompanying increase in tissue acidosis. Hyperglycemia produces substantial increases in brain lactate during ischemia, Received September 6, 1989; accepted February 22, 1990. glycolytic inhibitor can block hyperglycemia-enhanced damage. 7 Measurement of interstitial pH and calculation of intracellular pH (pHj) during cerebral ischemia indicate that increased acidosis accompanies increased tissue lactate. -10Nevertheless, hyperglycemia studies are often restricted to comparisons of normoglycemic animals with animals that have been made hyperglycemic by one dose of glucose.2 -6 The dose-response relation between blood glucose and brain lactate over a wide range of blood glucose levels has not been well described in a model of severe cerebral ischemia. Furthermore, the relation between brain lactate and brain pHj during severe global ischemia has not been well characterized over an extensive range of hyperglycemia. The understanding of such relations is especially important in light of the recent finding that brain pathology may be enhanced more by lactic acidosis than by other types of acidosis. 11In these experiments, the relation between plasma glucose, brain lactate, and intracellular pH is described over a wide...

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