enisoprost and Burns

Balb/c mice were transfused with .2 mL of C3H/HeJ mouse blood. 5 days later, the mice were gavaged with 10(10) 14C-labeled Escherichia coli, and a 20% full thickness flame burn was inflicted. Additional animals were treated with enisoprost (prostaglandin E1 (PGE1) analog) 200 micrograms/kg/day orally for 3 days before burn. Bacterial translocation was determined by both radionuclide counts (dpm) and viable colony counts 24 h post burn. Neutrophil accumulation was evaluated by the measurement of myeloperoxidase (MPO) in the liver. In addition, splenic macrophages were separated and cultured for 24 h with or without 10 micrograms/mL of LPS. Tumor necrosis factor, interleukin-1 (IL-1), IL-6, and PGE2 were measured in the cell culture supernatants. Consistent with previous work, enisoprost significantly reduced translocation. MPO in the liver was significantly greater in the control group compared to the enisoprost group. There was a significant correlation between MPO content and the degree of bacterial translocation (p < .05). Lipopolysaccharide-stimulated macrophage production of IL-1, IL-6, and PGE2 were significantly greater in the enisoprost group.

Topics: Alprostadil; Animals; Bacterial Physiological Phenomena; Blood Transfusion; Burns; Chemotaxis, Leukocyte; Dinoprostone; Escherichia coli; Female; Interleukin-1; Interleukin-6; Intestinal Mucosa; Intestines; Liver; Macrophages; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Multiple Organ Failure; Neutrophils; Peroxidase; Tumor Necrosis Factor-alpha

The aim of this study was to investigate the ability of two prostaglandin E1 (PGE1) analogues, misoprostol and enisoprost, to alter bacterial translocation following burn injury. Balb/c mice were treated with misoprostol (n = 36) or enisoprost (n = 36) for 3 days with different doses (20 or 200 micrograms/kg/day) prior to receiving a 20% full-thickness burn and simultaneous gavage with 1 x 10(10) 14C-Escherichia coli. Animals were sacrificed 4 and 24 hr postburn, and blood, peritoneal fluid, mesenteric lymph nodes, spleen, liver, and lungs were harvested aseptically. Radionuclide counts, number of viable bacteria, and percentage of translocating bacteria remaining alive in each tissue suggested that the high doses of misoprostol or enisoprost decreased the magnitude of 14C-E. coli translocation, while the low dose of both drugs enhanced bacterial clearance. Therefore, both misoprostol and enisoprost reduce bacterial translocation, and modulate bacterial clearance in a dose-dependent manner.

Topics: Alprostadil; Animals; Ascitic Fluid; Burns; Carbon Radioisotopes; Cell Movement; Escherichia coli; Female; Immunity; Intestinal Mucosa; Intestines; Liver; Lung; Mice; Mice, Inbred BALB C; Misoprostol; Spleen

Bacterial translocation and related mortality rates were examined in previously transfused BALB/c mice that were gavaged with 14C radioisotope-labeled Escherichia coli before inflicting a 20% full-thickness flame burn. Radionuclide counts were measured in blood obtained by retro-orbital puncture 4 hours postburn, and survival was recorded for 10 days. Radionuclide counts in the blood correlated well with both radionuclide counts and numbers of viable bacterial in the tissues. Survivors had significantly less bacterial translocation as evidenced by blood radionuclide counts compared with nonsurvivors, and there was a significant inverse correlation between the degree of translocation and the length of survival. In the next experiment, the prostaglandin E (PGE) analogs misoprostol, enisoprost, or 16,16-dimethyl PGE2 were administered to transfused animals for 3 days before burn. Prostaglandin E analogs significantly reduced bacterial translocation as measured by blood radionuclide counts 4 hours postburn and improved survival. The data demonstrate that the intensity of bacterial translocation after burn injury is significantly associated with subsequent death. Improvement of survival by PGE analogs is associated with decreased bacterial translocation.

Topics: 16,16-Dimethylprostaglandin E2; Alprostadil; Animals; Burns; Colony Count, Microbial; Escherichia coli; Female; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Misoprostol; Prostaglandins E, Synthetic