TOPICAL KETAMINE INHIBITS ALBUMIN EXTRAVASATION IN CHEMICAL PERITONITIS IN RATS

Background. As ketamine has local anaesthetics actions and local anaes thetics are known to have anti-inflammatory effects, ketamine could be expected to be an anti-inflammatory agent. Here we sought to determin e whether ketamine is indeed anti-inflammatory in chemical peritonitis induced by HCl in rats. Methods. Peritonitis was elicited by applying 0.02 M HCl on the surface of the cecum or appendix and quantified by measuring the extravasation of intravenously injected Evan's Blue boun d to albumin extracted From those tissues. Three experimental sets wer e performed. In the first set, four groups of 10 rats each received: 1 %, 2%, and 4% ketamine and 1% lidocaine. In the same animal, before in duction of peritonitis one area was topically pre-created with 0.9% sa line (control site) and another area was topically pre-treated with 1% , 2% or 4% ketamine or 1% lidocaine (experimental site). In the second set, two groups of 10 rats each received: 2% ketamine or 1% lidocaine . Ten min after the induction of peritonitis, the control site was top ically treated with 0.9% saline, while the experimental site was treat ed with 2% ketamine or 1% lidocaine. In the third set 20 rats, divided into two groups, were pre-treated either with 2% S(+)ketamine or 2% R (-)ketamine before the induction of peritonitis instead of the previou sly employed racemic version of the drug. Results. Treatment of the ce cum or appendix areas with ketamine or lidocaine before the induction of peritonitis decreased the extravasation of Evan's Blue-albumin from 5.7 +/- 0.7 mu g/100 mg tissue to 4.5 +/- 0.8, N.S. with 1% ketamine; from 5.9 +/- 0.8 to 4.1 +/- 0.7, P<0.01 with 2% ketamine; from 4.8 +/ - 0.7 to 3.5 +/- 0.6, P<0.05 with 1% ketamine and from 5.9 +/- 0.6 to 3.6 +/- 0.8, P<0.01 with 1% lidocaine. Treatment of the areas of perit onitis with 2% ketamine or 1% lidocaine decreased the extravasation of Evan's Blue-albumin from 5.6 +/- 0.5 mu g/100 mg tissue to 4.4 +/- 0. 6, P<0.05 and from 6.0 +/- 0.8 to 5.0 +/- 0.7, P<0.01. Administration of the isomer S(+)ketamine to colonic areas before the induction of pe ritonitis reduced the extravasation of Evan's Blue-albumin from 6.5 +/ - 0.7 mu g/100 mg tissue to 4.1 +/- 0.6, P<0.01; while the isomer R(-) ketamine was inactive. Conclusions. These results indicate that topica lly applied ketamine inhibited the development of chemical peritonitis . This action of racemic ketamine was due to the isomer S(+)ketamine.