Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms
D. B. Allen, J. J. Maguire, M. Mahdavian, C. Wicke, L. Marcocci, H. Scheuenstuhl, M. Chang, A. X. Le, H. W. Hopf and T. K. Hunt
Department of Anesthesia, University of California, San Francisco, USA.
BACKGROUND: "Respiratory burst" activity, ie, O2- production, is dependent
on PO2, temperature, pH, and glucose concentrations within the physiologic
range. OBJECTIVES: To determine whether environmental conditions
characteristic of wounds may limit human neutrophil respiratory burst
metabolism and to clarify the degree to which bactericidal oxidant
production depends on local PO2. METHODS: Human blood and wound neutrophils
were stimulated with phorbol myristate acetate. Oxygen consumption and
superoxide production were measured over a range of 30 to 300 mm Hg PO2, 0
to 40 mmol/L glucose, pH 6.0 to 8.0, and 30 degrees C to 37 degrees C. The
apparent Michaelis Menten constant for oxidant production with respect to
PO2 was calculated. RESULTS: Oxygen consumption and O2- production were
dependent on PO2 throughout the range tested. Half-maximal oxidant
production occurred in the range of 45 to 80 mm Hg PO2 and maximal at PO2
higher than 300 mm Hg. These data agree with the highest previous
estimates. Oxidant generation was also dependent on pH, temperature, and
glucose concentration, but to a lesser extent. CONCLUSIONS: Leukocyte
bacterial killing capacity as measured by oxygen consumption and superoxide
production are substantially impaired at the low oxygen tensions often
found in wounds. Changes in pH, temperature, and glucose concentration have
lesser but nonetheless significant consequences. The data provide a
plausible mechanism for the vulnerability of some wounds to infection and
for the previous finding that increasing oxygen tension at wound sites
enhances bactericidal function. Thus, the data serve as a basis for future
studies on prevention of wound infection.