Elimination of 2-arachidonoylglycerol action by direct hemoperfusion through immobilized polymyxin B fibers: an experimental study in conscious guinea pigs.

Direct hemoperfusion through a network of immobilized polymyxin B fibers is used for the treatment of septic shock, but the mechanism underlying the clinical benefits remains unclear. The aims of the present study were to assess the actions of direct hemoperfusion through immobilized polymyxin B fibers on effects of exogenous endotoxin or 2-arachidonoylglycerol in conscious guinea pigs; and to examine the underlying mechanisms. In the present study, colonic motion was monitored continuously by telemetry using a force transducer attached to the taenia caecum, while blood pressure was monitored with a carotid artery catheter. To establish a hemoperfusion circuit in a freely moving, conscious guinea pig, catheters were implanted in the carotid artery and the jugular vein, tunneled subcutaneously, exteriorized at the back of the neck in contact with a lightweight tethering spring, and attached to a swivel device at the top of the cage. On the day after the operation, lipopolysaccharide (Escherichia coli, O111:B4; 1 mg/kg) or 2-arachidonoylglycerol (1 mg/kg) was given intraperitoneally (i.p.) and direct hemoperfusion through immobilized polymyxin B fibers was carried out for 2 h. The results showed that in guinea pigs treated with direct hemoperfusion through immobilized polymyxin B fibers, relaxation of colonic longitudinal muscle caused by lipopolysaccharide or 2-arachidonoylglycerol was significantly suppressed, as were decreases in blood pressure. We conclude that the actions following exogenous administration of 2-arachidonoylglycerol were eliminated by direct hemoperfusion through immobilized polymyxin B fibers. These results suggest that effectiveness of direct hemoperfusion through immobilized polymyxin B fibers in endotoxemia involves elimination of 2-arachidonoylglycerol action.