Morphine attenuates leukocyte/endothelial interactions

Gram-negative sepsis and subsequent endotoxic shock after surgery remain pr oblematic in the United States and throughout the world. While morphine is widely prescribed for postoperative trauma pain management, there are repor ts that morphine may compromise the immune system and contribute to postope rative sepsis. The current study tested the hypothesis that morphine attenu ates leukocyte rolling and sticking in both arterioles and venules via nitr ic oxide production. Nude mice implanted with slow-release morphine pellets were used in this study. The dorsal skinfold chamber model for intravital fluorescence microscopy on awake mice was used. Leukocyte/endothelial inter actions were evaluated after bolus injection of oxidized low density lipopr otein. Morphine was found to significantly attenuate leukocyte rolling and sticking in both the arterial and venular side of the microcirculation. Thi s attenuation was reversed by simultaneous implantation of naloxone pellets . The mechanisms of this attenuation were further investigated by administr ation of the nitric oxide synthase inhibitors NG-nitro-L-arginine (NOLA) an d aminoguanidine (AIS) in drinking water, NOLA was found to significantly r everse this morphine-induced attenuation of leukocyte rolling and sticking in both arterioles and venules, However, AG did not have the same effect. T he results indicate that morphine interferes with leukocyte/endothelial cel l interactions via stimulation of nitric oxide production. (C) 2000 Academi c Press.