R-100 improves pulmonary function and systemic fluid balance in sheep with combined smoke-inhalation injury and Pseudomonas aeruginosa sepsis

Background: Septic shock is a major cause of death in intensive care units around the world. The aim of the study was to investigate whether the novel drug R-100 (a superoxide degradation catalyst and nitric oxide donor) improves pulmonary function in a sheep model of septic shock caused by Pseudomonas aeruginosa and smoke inhalation. Methods: Eleven female sheep were prepared surgically and randomly assigned to a treatment group (n = 5) or a control group (n = 6) after inhalation of cooled cotton smoke and airway instillation of live P. aeruginosa (2.5 × 10 ¹¹ CFU) by bronchoscope under deep anesthesia and analgesia. The treatment group received an intravenous infusion of a total of 80 mg/kg of R-100 diluted in 500 mL of 5% dextrose. The control group was given 500 mL of 5% dextrose. All animals received intravenous lactated Ringer's solution to maintain a hematocrit level at baseline ± 3%. Blood gas and hemodynamics were measured at baseline and then analyzed every 3 h during the 24-h study period. Results are expressed as mean ± SEM. Results: The treated animals showed significant improvement in their pulmonary gas exchange (PaO ₂ /FiO ₂ ratio at 24 h: 246 ± 29 vs. 90 ± 40 mmHg control, P < 0.05). Pulmonary arterial pressures were reduced in the treated group (24 h: 26 ± 1 vs. 30 ± 2 cm mmHg control, P < 0.05). The treated animals also had an improved total fluid balance after 24 h (190 ± 45/24 h mL vs. 595 ± 234/24 h mL control, P < 0.05). Conclusions: Treatment with R-100 improves pulmonary gas exchange and blood oxygenation, and prevents a fluid imbalance in sheep subjected to smoke inhalation and P. aeruginosa.