Both surgical trauma and infection can disturb the proteinase to proteinase inhibitor balance in the circulation. We sought to assess the effect of Candida albicans infection (INFX) on postoperative mortality, to correlate mortality with total serum proteolytic activity (PA), and to assess the impact of exogenous proteinase inhibitors (PI) on this mortality. Mice underwent midline laparotomy (LAP) and immediate postoperative intravenous C. albicans infection. LAP + INFX shortened mean survival compared to INFX or LAP alone. Quantitative renal cultures confirmed that death in the LAP + INFX and INFX groups was due to Candida sepsis. PA was measured using an 125I-labeled protein assay, yielding micrograms of acid-soluble peptides/100 μl of serum. In control, sham-operated, and LAP groups, PA averaged <9.0, and mortality was 0. In INFX and LAP + INFX groups, PA averaged > 14.5 and mortality was high. To determine if high PA was related to high mortality, LAP + INFX mice were treated immediately preoperatively with a single dose of PI (1 mg α1-proteinase inhibitor, 1 mg antithrombin, and 1000 KIU aprotinin). Mean survival increased with PI treatment. In conclusion, the addition of Candida infection to surgical trauma hastened mean time to death. More rapid death correlated with elevated PA and may reflect systemic imbalance in the proteinase to proteinase inhibitor ratio in the circulation. PI improved survival, suggesting that proteinase inhibition may prove useful in the future in the treatment of fungal sepsis in surgical patients.
ASJC Scopus subject areas