Effects of pneumonectomy on nitric oxide synthase expression and perivascular edema in the remaining lung of rats

Abstract

Pneumonectomy is associated with high mortality and high rates of complications. Postpneumonectomy pulmonary edema is one of the leading causes of mortality. Little is known about its etiologic factors and its association with the inflammatory process. The purpose of the present study was to evaluate the role of pneumonectomy as a cause of pulmonary edema and its association with gas exchange, inflammation, nitric oxide synthase (NOS) expression and vasoconstriction. Forty-two non-specific pathogen-free Wistar rats were included in the study. Eleven animals died during or after the procedure, 21 were submitted to left pneumonectomy and 10 to sham operation. These animals were sacrificed after 48 or 72 h. Perivascular pulmonary edema was more intense in pneumonectomized rats at 72 h (P = 0.0131). Neutrophil density was lower after pneumonectomy in both groups (P = 0.0168). There was higher immunohistochemical expression of eNOS in the pneumonectomy group (P = 0.0208), but no statistically significant difference in the expression of iNOS. The lumen-wall ratio and pO2/FiO2 ratio did not differ between the operated and sham groups after pneumonectomy. Left pneumonectomy caused perivascular pulmonary edema with no elevation of immunohistochemical expression of iNOS or neutrophil density, suggesting the absence of correlation with the inflammatory process or oxidative stress. The increased expression of eNOS may suggest an intrinsic production of NO without signs of vascular reactivity

Effect of methylprednisolone on perivascular pulmonary edema, inflammatory infiltrate, VEGF and TGF-beta immunoexpression in the remaining lungs of rats after left pneumonectomy

“…Although a surgical procedure can trigger an inflammatory process, the neutrophil infiltrate is reduced 48 and 72 h after pneumonectomy (8). Despite the well-known effect of corticosteroid on neutrophil migration, we observed only a trend to a reduction of the neutrophil infiltrate after corticosteroid administration, which was not statistically significant.…”

“…In the present experimental model, as described before, the pO 2 /FiO 2 ratio showed absence of functional loss after pneumonectomy. Similarly, the administration of corticosteroid before the operation did not improve the levels of pO 2 after pneumonectomy (8).…”

“…In a previous study, we observed the formation of pulmonary perivascular edema in rats after left pneumonectomy without evidence of oxidative stress related to nitric oxide synthase or neutrophil migration (8). In the present study, we analyzed the effect of methylprednisolone on the partial O 2 pressure (pO 2 )/inspired O 2 fraction (FiO 2 ) ratio, pulmonary perivascular edema, neutrophil infiltrate, and the expression of TGF-β and VEGF in the remaining lung of rats after left pneumonectomy.…”

“…An index for semiquantitative quantification of perivascular pulmonary edema (perivascular edema index) was calculated on the basis of the relationship between the perivascular area and the vascular area (Figure 1), as described in Ref. 8.…”

“…A manual count of neutrophils present in the alveolar septa was performed by an observer blind to the study. Twenty non-coincident fields, enlarged to 400X, were quantified by the point-counting technique (8,10).…”