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Effect on Mortality Rate in a Septic Rat Model

Richard A. Pearce, MD; Richard J. Finley, MD, FRCS(C); Robert A. Mustard, Jr, MD, FRCS(C); John H. Duff, MD, FRCS(C)

Arch Surg. 1985;120(8):937-940.

Abstract
• Neutrophil-derived oxygen-free radicals may play a role in organ dysfunction associated with generalized sepsis. A rat model was used to test the effects of two free radical scavengers, dimethyl sulfoxide (DMSO) and 2,3-dihydroxybenzoic acid (2,3-DHB), on mortality from intra-abdominal sepsis produced by cecal ligation and perforation. Being an iron-chelating agent, 2,3-DHB may have an additional bacteriostatic effect. Therapeutic regimens included no treatment; gentamicin sulfate (2 mg given intraperitoneally [IP] every eight hours); DMSO (2 g/24 hr given IP every eight hours in divided doses); 2,3-DHB (35 mg/kg given IP every eight hours); and combinations of gentamicin with each free radical scavenger. No statistically significant improvement in survival was obtained by therapeutic intervention with gentamicin alone, DMSO alone, 2,3-DHB alone, or gentamicin in combination with DMSO. When used in combination with gentamicin, 2,3-DHB yielded a statistically significant improvement in survival when compared with gentamicin alone or with no treatment. These results show that 2,3-DHB when used in combination with gentamicin has a beneficial effect on mortality following intra-abdominal sepsis in this model.

(Arch Surg 1985;120:937-940)

Author Affiliations
From the Department of Surgery, University of Western Ontario, London. Dr Mustard is a Fellow of the Medical Research Council of Canada.

Footnotes
Accepted for publication Dec 12, 1984.

Presented before the Fourth Annual Meeting of the Surgical Infection Society, Montreal, April 30, 1984.

Reprint requests to Department of Surgery, Wellesley Hospital, 160 Wellesley St E, Toronto, Ontario, Canada M6A 5A5 (Dr Mustard).

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