Abstract
BackgroundSeptic 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.MethodsEleven 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.ResultsThe 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).ConclusionsTreatment with R-100 improves pulmonary gas exchange and blood oxygenation, and prevents a fluid imbalance in sheep subjected to smoke inhalation and P. aeruginosa.
Highlights
Septic shock is a major cause of death in intensive care units around the world
Body weight was similar in both groups (35.4 ± 0.8 kg in the treatment group vs. 35.2 ± 0.9 kg in the control), and there were no differences in body surface area between the groups (0.91 ± 0.01 m2 in the treatment group vs. 0.91 ± 0.01 m2 in the control)
The arterial COHb determined immediately after the smoke-inhalation injury averaged 69.1 ± 2.0% in the control group and 64.4 ± 2.5% in the R-100 group; these levels were not significantly different from each other indicating a similar degree of injury
Summary
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. It is well known that patients with acute lung injury (ALI), who develop sepsis have a poor prognosis [1, 2]. Excessive NO, especially iNOS-derived, is generally regarded as detrimental in sepsis pathophysiology, studies have instead shown that non-selective inhibition of NO production may cause pulmonary. It is worth noting that increased pressure in pulmonary circulation during sepsis is associated with a reduced patient survival [13]. Numerous studies besides our own have shown that administration of inhaled NO may normalize increased pulmonary arterial pressure [14,15,16]
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