Acute Hyperoxic Lung Edema Is Not Reduced by Granulocyte Depletion in Rats

Abstract

In order to study the role of neutrophils in hyperoxic lung edema, we induced a sustained granulocytopenia in rats by giving them a single intraperitoneal injection of 50 mg · kg”1 cyclophosphamide (CY) (CY-injected rats). Hyperoxic lung damage (FIO₂ = 1.0, 60 h) was assessed by measuring pulmonary water (PW). Exposure to hyperoxia coincided with the granulocytopenic period. After exposure to hyperoxia, the difference in PW between CY- and 0.09% saline solution-injected (S-injected) rats was not significant (PW (g) (x ± 1 SD): CY-injected rats: 1.49 ± 0.09; S-injected rats: 1.68 ± 0.09, NS). If neutrophils have a pathogenic role in hyperoxic lung injury, the absence of edema reduction in neutropenic rats could be explained by pulmonary infection, insufficient neutrophil depletion or cumulative lung toxicity of CY and oxygen. No pulmonary infectious agents could be detected in lung and bronchoalveolar lavage cultures. Although already severe, the neutrophil depletion was intensified by a second injection of CY (50 mg · kg”1). After exposure to hyperoxia, the number of neutrophils in lung lavage was much lower in these neutropenic rats (156 · 103 ± 33 · 103) than in S-injected rats (571 103 ± 100–103) (p < 0.001), but no significant reduction of PW was observed. No significant increase was observed in either PW or dry lung weight in CY-injected rats not exposed to hyperoxia. CY alone might not be responsible for the absence of edema reduction, but might amplify the toxic effects of oxygen on the lung. In conclusion, we could not demonstrate any reduction of lung edema due to granulocyte depletion. The role of neutrophils in hyperoxic lung injury has yet to be fully elucidated.

Pentoxifylline does not protect against hyperoxic lung injury in rats

“…lung injury in hyperoxia [4,5], there is also data to suggest that hyperoxic lung injury may occur in the absence of neutrophils, as shown in a previous study, where neutrophil depletion by cyclophosphamide did not affect lung oedema in rats exposed to hyperoxia [23]. The production of free radicals has been shown to contribute significantly to hyperoxia-induced lung injury, and a number of studies have shown an improvement in survival with the use of free radical scavengers.…”

Use of Iron Chelators in Preventing Hydroxyl Radical Damage: Adult Respiratory Distress Syndrome as an Experimental Model for the Pathophysiology and Treatment of Oxygen-Radical-Mediated Tissue Damage

“…Increased concentrations of GSH have also been found in the BAL fluid of hyperoxic rats [143]. In dogs, N-acetylcysteine, which induces the synthesis of GSH, had a beneficial effect on lung histology and on the hemodynamic changes caused by 100% oxy gen [144], Granulocytes are not essential for the develop ment of ARDS caused by hyperoxia [145], although lung injury becomes more serious during resolution of neutro penia [146], Adherence of neutrophils to endothelium is increased during hyperoxia [147], which is associated with the release of chemotactic factors from endothelial cells [148] and cytokines from alveolar macrophages [149],…”