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.
Bibliographical noteFunding Information:
The authors thank the staff of the Translational Intensive Care Unit at the University of Texas Medical Branch for their valuable assistance in conducting these studies. We would like to acknowledge the contributions of the late Dr. Daniel Traber and Mrs. Lillian Traber. Funded through Grants SCH84050, SHC85500, NIH GM097480, and through Radikal Therapeutics, inc. The funding agencies had no role in the study design or execution.
© 2017 The Author(s).
Copyright 2019 Elsevier B.V., All rights reserved.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)