INHIBITION OF NITRIC-OXIDE SYNTHASE DOES NOT AFFECT SURVIVAL IN A RATMODEL OF ABDOMINAL SEPSIS

The effect of inhibiting nitric oxide (NO) synthesis during sepsis was studied in a caecal perforation model on Wistar rats. This model indu ces severe abdominal sepsis with a 48-h mortality >90% in untreated an imals. The survival time in hours (median values with the 95% confiden ce intervals in parentheses) for the control group was 15 (11.5-27.0)h . Treatment with the inhibitors of NO synthesis, N-G-monomethyl-L-argi nine (LNMMA), 30 mg kg(-1) body weight (BW) or S-(2-aminoethyl)-isothi ourea (AET), 3 mg kg(-1) BW, given either once or twice after sepsis i nduction did not affect survival in this model. Survival time when LNM MA was given once was 13 (11-22)h and when given twice it was 14 (8-41 ) h. The corresponding survival times were 9 (4-28)h and 11 (5-27)h fo r treatment with AET. In conclusion, this study demonstrates that surv ival in the present model of live multiplying bacterial sepsis is not affected by either LNMMA or AET. Testing the potential clinical effect s of inhibition of NO synthesis during sepsis should not be confined t o short-term studies of haemodynamic changes induced by lipopolysaccha ride.