Topical ketamine inhibits albumin extravasation in chemical peritonitis in rats.
BACKGROUND
As ketamine has local anaesthetic actions and local anaesthetics are known to have anti-inflammatory effects, ketamine could be expected to be an anti-inflammatory agent. Here we sought to determine 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 bound to albumin extracted from those tissues. Three experimental sets were 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 induction of peritonitis one area was topically pre-treated with 0.9% saline (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 topically treated with 0.9% saline, while the experimental site was treated 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 previously employed racemic version of the drug.


RESULTS
Treatment of the cecum 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 micrograms/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 4% ketamine and from 5.9 +/- 0.6 to 3.6 +/- 0.8, P < 0.01 with 1% lidocaine. Treatment of the areas of peritonitis with 2% ketamine or 1% lidocaine decreased the extravasation of Evan's Blue-albumin from 5.6 +/- 0.5 micrograms/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 peritonitis reduced the extravasation of Evan's Blue-albumin from 6.5 +/- 0.7 micrograms/100 mg tissue to 4.1 +/- 0.6, P < 0.01; while the isomer R(-)ketamine was inactive.


CONCLUSIONS
These results indicate that topically applied ketamine inhibited the development of chemical peritonitis. This action of racemic ketamine was due to the isomer S(+)ketamine.
Hirota
K
K
Department of Anaesthesiology, University of Illinois College of Medicine at Chicago, USA.
Zsigmond
E K
EK
Matsuki
A
A
Rabito
S F
SF
D000287:Administration, Topical; D000418:Albumins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001065:Appendix / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002432:Cecum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006851:Hydrochloric Acid / Q000009:adverse effects; D007536:Isomerism; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008012:Lidocaine / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005070:Evans Blue; D007649:Ketamine; D008012:Lidocaine; D006851:Hydrochloric Acid