KETAMINE ATTENUATES ENDOTOXIN-INDUCED LEUKOCYTE ADHERENCE IN RAT MESENTERIC VENULES

Objectives: To determine the influence of ketamine on endotoxin-induce d leukocyte adherence and venular microhemodynamics. Design: Randomize d, controlled trial. Setting: Experimental laboratory. Subjects: Thirt y male Wistar rats. Interventions: The rats were pretreated with ketam ine (10 mg/kg iv) or 0.9% saline, and both groups were given endotoxin (Escherichia coli lipopolysaccharide; 5 mg/kg iv). The control group received two doses of 0.9% saline. Measurements and Main Results: The rates of leukocyte adherence and changes in microhemodynamics were mon itored in rat mesenteric venules, using in vivo video microscopy, The number of adherent leukocytes was determined on-line in 10-min interva ls from 60 mins before until 2 hrs after endotoxin administration. Ven ular diameters, red blood cell velocity, volumetric blood flow, and th e venular wall shear rate were monitored before and at 10, 30, and 60 mins after endotoxin exposure. A 6.3-fold increase in the number of ad herent leukocytes was observed 10 mins after administration of endotox in when compared with control animals (5.87 +/- 0.69 vs. 0.93 +/- 0.21 adherent cells/100 mu m; p <.001), This increase remained unchanged f or 120 mins. In ketamine-pretreated rats, a 2.6-fold increase in leuko cyte adherence occurred during the first 20 mins after endotoxin expos ure (2.40 +/- 0.46 vs, 0.93 +/- 0.21 adherent cells/100 mu m; p < .01) . However, no difference in the number of adherent leukocytes between ketamine-pretreated and control animals was found after this 20-min pe riod. In animals of the control group, no increase in leukocyte adhere nce occurred during the entire observation time. Diameters of mesenter ic venules did not change after endotoxin exposure in any of the group s. Red blood cell velocity and venular blood flow in the endotoxin-tre ated groups decreased 10 mins after the injection of endotoxin when co mpared with controls, but these values did not show any difference whe n they were compared between ketamine and saline-pretreated animals. S imilarly, venular wall shear rate in the endotoxin-treated groups decr eased 10 and 30 mins after injection of endotoxin, However, no signifi cant difference occurred between ketamine and saline-pretreated animal s. Conclusions: Pretreatment with ketamine attenuates endotoxin-induce d leukocyte adherence by a shear rate-independent mechanism, suggestin g reduced expression of adhesion molecules. These results indicate tha t ketamine exerts an anti-inflammatory effect, which might be benefici al in septic patients.