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. 2017 Dec 28;15(1):266.
doi: 10.1186/s12967-017-1366-6.

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

Hiroshi Ito  1 , Erik Malgerud  1 , Sven Asmussen  1 , Ernesto Lopez  1 , Andrew L Salzman  2 , Perenlei Enkhbaatar  3
Affiliations

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

Hiroshi Ito et al. J Transl Med. .

Abstract

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 × 1011 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 (PaO2/FiO2 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.

Keywords: R-100; Redox; Sepsis; Smoke.

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Figures

Fig. 1
Fig. 1
Effects of R-100 on pulmonary gas exchange evaluated by PaO2/FiO2 ratio (a) and pulmonary shunt fraction (b). PaO2 is a oxygen partial pressure (mm Hg) in arterial blood. FiO2 represents oxygen partial pressure (mm Hg) in inspired air. Data are expressed as mean ± SEM. *P < 0.05 vs. control
Fig. 2
Fig. 2
Effects of R-100 on airway peak (a) and pause (b) pressures. Data are expressed as mean ± SEM. *P < 0.05 vs. control
Fig. 3
Fig. 3
Effects of R-100 on fluid output (urinary output) (a) and fluid input (intravenous lactated Ringer’s solution) (b). Data are expressed as mean ± SEM
Fig. 4
Fig. 4
Effects of R-100 on total body fluid accumulation over time. Data are expressed as mean ± SEM. *P < 0.05 vs. control
See this image and copyright information in PMC

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