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Ibuprofen and prostanoid release
451
Abstracts
Septic drugs
challenges
and immunomodulating
Caecal ligation and puncture was inflicted on burned mice to measure their resistance to an infectious challenge. Such treatment markedly reduced the survival rate from 63.7 to 20 per cent when carried out on day 10 after burning, but was ineffective if carried out on days 5 or 21 after burning. Other burned animals receiving caecal ligation and puncture were pretreated with either systemic cimetidine, ibuprofen, cyclophosphamide or topical cerium nitrate in carefully defined dosages and survival rates were again determined on post-burn day 10. All four immunomodulating compounds significantly improved the survival rates at this time compared with the findings in burned untreated animals. Zapata-Sirvent R. L., Hansbrough J. F., Bender E. M. et al. (19X6) Post-burn immunosuppression in an animal model. 4. Improved resistance to septic challenge with immunomodulating drugs. Surgery 99, (I), 53.
ibuprofen and prostanoid
release
In sheep with full skin thickness burns a local injection of E. coli endotoxin increased the tissue prostanoid content, which in turn induced an increase in pulmomary artery pressure, a decrease in mean arterial oxygen tension (Pao?) and an increased venous plasma content of thromboxane. In lymph the prostanoid content increased 10 to 15 times. An i.v. infusion of ibuprofen eliminated the increases in pulmonary artery pressure and lymph prostanoid content and the decrease in Paoz; however, the plasma prostanoid contents were decreased to subnormal potentially deleterious levels. Topically applied ibuprofen cream prevented the pulmonary dysfunction and the rise in plasma thromboxane levels and limited the burn lymph prostanoid content to only three to five times normal. The ibuprofen cream softened the eschar allowing a lOOO-fold increase in wound bacterial content. This deleterious effect could probably have been prevented by the incorporation of an antibacterial agent in the cream. Katz A., Ryan P., Lalonde C. et al. (1986) Topical ibuprofen decreases thromboxane release from the endotoxin stimulated burn wound. J. Trauma 26, (2), 157.
Smoke inhalation
studies in rabbits
Anaesthetized rabbits inhaled smoke (cooled to room temperature) from burning cotton for three sessions each of 2 to 3min. Such smoke inhalation produced a mean COHb level of 48 per cent, although the differences between pre- and post-inhalation PO, and Pcoz values were not significantly different. Lung tissue removed 24 h after smoke inhalation showed extensive loss of tracheal epithelium often extending down to the terminal bronchi. There was also considerable oedema and increased migration of polymorphonuclear cells. By l&l4 days after smoke inhalation there was reparative epithelial cell growth in the
trachea and major bronchi in spite of persisting inflammation and loss of intralobar bronchi. Inflammatory exudate extended into the alveoli. The increased vascular permeability associated with these lung tissue changes was measured using ‘)“m Tc““Tc-labelled dextran and a labelled erythrocytes, scintillation camera. Increased vascular permeability was shown by the increased pulmonary extraction of the labelled dextran compared to that of the reference tracer (labelled erythrocytes). Rowland R. R. R.. Yamaguchi K. T., Santibanez A. S. et al. (1986) Smoke inhalation model for lung permeability studies. J. Trauma 26, (2), 153.
Immunization with Pseudomonas aefuginosa flagellae antigens Mice were immunized with the two antigenic types of flagellae derived from strains of Ps. aeruginosa. Subsequent burning and infecting of these mice with whole live organisms of Ps. neruginosa indicated that they were protected from fatal sepsis. Protection was spccific for the flagella antigen of the challenge strain but independent of its somatic origin. When both antigens were used together for immunization protection was independent of both the flagella and somatic antigens of the challenge strain. Thus a divalent Ps. aeruginosu flagella vaccine might be of value for immunizing burned patients. Holder I. A. and Naglich J. G. (1986) Experimental studies of the pathogenesis of infections due to Pseudomonad aeruginosa. Immunization using divalent flagella preparations. J. Truumo 26, (2), 118.
Oxygen utilization
and CO poisoning
The toxic effects of the inhalation of 0.50 per cent carbon monoxide (CO) in air were measured in six dogs and compared with the effects of the inhalation of an air-nitrogen mixture in another six dogs which produced a similar decrement of arterial oxyhaemoglobin saturation. Measurements of arterial and mixed venous blood gases, thermal dilution cardiac output and arterial and venous oxy- and carboxy-haemoglobin saturation were measured. Oxygen consumption and extraction rates were also calculated. There were no significant differences in oxygen consumption or extraction in the two groups of animals subjected to equivalent reductions in arterial haemoglobin levels, despite the use of CO to produce desaturation in one group. This CO poisoning is mainly a hypoxic lesion with COHb replacing 0,Hb. Halebian P., Robinson N., Barie P. et al. (1986) Whole body oxygen utilisation during acute carbon monoxide poisoning and isocapneic nitrogen hypoxia. J. Trauma 26, (2), 110.
Haemodynamic
and respiratory
changes
Haemodynamic and respiratory changes were studied in sheep with deep burns covering 40 per cent of the body surface, half of which were maintained in an anaesthetized state post-burn and half of which were allowed to recover consciousness. Compared with the
Abstracts
Septic drugs
challenges
and immunomodulating
Caecal ligation and puncture was inflicted on burned mice to measure their resistance to an infectious challenge. Such treatment markedly reduced the survival rate from 63.7 to 20 per cent when carried out on day 10 after burning, but was ineffective if carried out on days 5 or 21 after burning. Other burned animals receiving caecal ligation and puncture were pretreated with either systemic cimetidine, ibuprofen, cyclophosphamide or topical cerium nitrate in carefully defined dosages and survival rates were again determined on post-burn day 10. All four immunomodulating compounds significantly improved the survival rates at this time compared with the findings in burned untreated animals. Zapata-Sirvent R. L., Hansbrough J. F., Bender E. M. et al. (19X6) Post-burn immunosuppression in an animal model. 4. Improved resistance to septic challenge with immunomodulating drugs. Surgery 99, (I), 53.
ibuprofen and prostanoid
release
In sheep with full skin thickness burns a local injection of E. coli endotoxin increased the tissue prostanoid content, which in turn induced an increase in pulmomary artery pressure, a decrease in mean arterial oxygen tension (Pao?) and an increased venous plasma content of thromboxane. In lymph the prostanoid content increased 10 to 15 times. An i.v. infusion of ibuprofen eliminated the increases in pulmonary artery pressure and lymph prostanoid content and the decrease in Paoz; however, the plasma prostanoid contents were decreased to subnormal potentially deleterious levels. Topically applied ibuprofen cream prevented the pulmonary dysfunction and the rise in plasma thromboxane levels and limited the burn lymph prostanoid content to only three to five times normal. The ibuprofen cream softened the eschar allowing a lOOO-fold increase in wound bacterial content. This deleterious effect could probably have been prevented by the incorporation of an antibacterial agent in the cream. Katz A., Ryan P., Lalonde C. et al. (1986) Topical ibuprofen decreases thromboxane release from the endotoxin stimulated burn wound. J. Trauma 26, (2), 157.
Smoke inhalation
studies in rabbits
Anaesthetized rabbits inhaled smoke (cooled to room temperature) from burning cotton for three sessions each of 2 to 3min. Such smoke inhalation produced a mean COHb level of 48 per cent, although the differences between pre- and post-inhalation PO, and Pcoz values were not significantly different. Lung tissue removed 24 h after smoke inhalation showed extensive loss of tracheal epithelium often extending down to the terminal bronchi. There was also considerable oedema and increased migration of polymorphonuclear cells. By l&l4 days after smoke inhalation there was reparative epithelial cell growth in the
trachea and major bronchi in spite of persisting inflammation and loss of intralobar bronchi. Inflammatory exudate extended into the alveoli. The increased vascular permeability associated with these lung tissue changes was measured using ‘)“m Tc““Tc-labelled dextran and a labelled erythrocytes, scintillation camera. Increased vascular permeability was shown by the increased pulmonary extraction of the labelled dextran compared to that of the reference tracer (labelled erythrocytes). Rowland R. R. R.. Yamaguchi K. T., Santibanez A. S. et al. (1986) Smoke inhalation model for lung permeability studies. J. Trauma 26, (2), 153.
Immunization with Pseudomonas aefuginosa flagellae antigens Mice were immunized with the two antigenic types of flagellae derived from strains of Ps. aeruginosa. Subsequent burning and infecting of these mice with whole live organisms of Ps. neruginosa indicated that they were protected from fatal sepsis. Protection was spccific for the flagella antigen of the challenge strain but independent of its somatic origin. When both antigens were used together for immunization protection was independent of both the flagella and somatic antigens of the challenge strain. Thus a divalent Ps. aeruginosu flagella vaccine might be of value for immunizing burned patients. Holder I. A. and Naglich J. G. (1986) Experimental studies of the pathogenesis of infections due to Pseudomonad aeruginosa. Immunization using divalent flagella preparations. J. Truumo 26, (2), 118.
Oxygen utilization
and CO poisoning
The toxic effects of the inhalation of 0.50 per cent carbon monoxide (CO) in air were measured in six dogs and compared with the effects of the inhalation of an air-nitrogen mixture in another six dogs which produced a similar decrement of arterial oxyhaemoglobin saturation. Measurements of arterial and mixed venous blood gases, thermal dilution cardiac output and arterial and venous oxy- and carboxy-haemoglobin saturation were measured. Oxygen consumption and extraction rates were also calculated. There were no significant differences in oxygen consumption or extraction in the two groups of animals subjected to equivalent reductions in arterial haemoglobin levels, despite the use of CO to produce desaturation in one group. This CO poisoning is mainly a hypoxic lesion with COHb replacing 0,Hb. Halebian P., Robinson N., Barie P. et al. (1986) Whole body oxygen utilisation during acute carbon monoxide poisoning and isocapneic nitrogen hypoxia. J. Trauma 26, (2), 110.
Haemodynamic
and respiratory
changes
Haemodynamic and respiratory changes were studied in sheep with deep burns covering 40 per cent of the body surface, half of which were maintained in an anaesthetized state post-burn and half of which were allowed to recover consciousness. Compared with the