Inhibition of nitric oxide synthase does not affect survival in a rat model 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 induces severe abdominal sepsis with a 48-h mortality > 90% in untreated animals. The survival time in hours (median values with the 95% confidence intervals in parentheses) for the control group was 15 (11.5-27.0) h. Treatment with the inhibitors of NO synthesis, NG-monomethyl-L-arginine (LNMMA), 30 mg kg-1 body weight (BW) or S-(2-aminoethyl)-isothiourea (AET), 3 mg kg-1 BW, given either once or twice after sepsis induction did not affect survival in this model. Survival time when LNMMA 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 for treatment with AET. In conclusion, this study demonstrates that survival in the present model of live multiplying bacterial sepsis is not affected by either LNMMA or AET. Testing the potential clinical effects of inhibition of NO synthesis during sepsis should not be confined to short-term studies of haemodynamic changes induced by lipopolysaccharide.
Strand
O A
OA
Department of Infectious Diseases, Ullevål Hospital, Oslo, Norway.
Kirkebøen
K A
KA
Giercksky
K E
KE
D000818:Animals; D002432:Cecum; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007416:Intestinal Perforation / Q000201:enzymology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000201:enzymology*; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D000338:beta-Aminoethyl Isothiourea; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase