Effects of cardiopulmonary bypass on lung nuclear factor-kappa B activity, cytokine release, and pulmonary function in dogs

Abstract

Objectives: To study the effect of cardiopulmonary bypass (CPB) on nuclear factor-kappa B (NF-κB) and cytokine expression and pulmonary function in dogs.

Materials and methods: Twelve male mongrel dogs were divided into a methylprednisolone group (group M) and a control group (group C). All animals underwent aortic and right atrial catheterization under general anesthesia. Changes in pulmonary function and hemodynamics were monitored and the injured site was histologically evaluated.

Results: The activity of NF-κB and myeloperoxidase (MPO), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8, and the wet/dry (W/D) weight ratio were significantly higher after CPB than before CPB in both groups (P<0.01), with the lower values in group M than in group C, at different time points (P<0.01). Histological evaluation revealed neutrophilic infiltration and thickening of the alveolar interstitium in both groups; however, the degree of pathological changes was significantly lower in group M than in group C. The alveolar-arterial O2 tension difference (PA-aDO2) was significantly higher after CPB than before CBP (P<0.01), and lower in group M than in group C (P<0.01). The pulmonary compliance after removal of the aortic clamp obviously decreased in group C (P<0.05), with no significant change in group M.

Conclusion: CPB can significantly enhance the activation of NF-κB in lung tissues and increase the expression of inflammatory cytokines, thus inducing lung injury. Methylprednisolone can inhibit the NF-κB activation, thus inhibiting the release of cytokines and protecting the lung function.

Keywords: Acute lung injury; Cardiopulmonary bypass Cytokines; Methyl-prednisolone; NF-κB.

Figure 1

Lung function changes (mean±SD). Impacts of CPB on lung compliance, PA-aO2, and PaCO2 between the two groups. Data are expressed as the mean±SD (n=5 per group). #P<0.05, ##P<0.01, compared with the control group; *P<0.05, **P<0.01, compared with the T0 (T0: before CPB, T2: 30 min after aortic clamp removal, and T3: 90 min after aortic clamp removal)

Figure 2

Changes of cytokines levels (mean±SD). Changes of NF-κB P₆₅ activities of the two groups before and after CPB. NF-κB P₆₅ activity was measured by the Western blot assay. NF-κB P₆₅ activity indicates the intensity of bands on Western blot (IOD). Data are expressed as the mean±SD, (n=5 per group). ^##P<0.01, compared with the control group; ^**P<0.01, compared with the T₀ (T₀: before CPB, T₁: before aortic clamp removal, T₂: 30 min after aortic clamp removal, and T₃: 90 min after aortic clamp removal)

Figure 3

Changes of NF-κB P₆₅ activity (mean±SD). Changes of NF-κB P65 activities of the two groups before and after CPB. NF-κB P65 activity was measured by the Western blot assay. NF-κB P65 activity indicates the intensity of bands on Western blot (IOD). Data are expressed as the mean±SD, (n=5 per group). ##P<0.01, compared with the control group; **P<0.01, compared with the T0 (T0: before CPB, T1: before aortic clamp removal, T2: 30 min after aortic clamp removal, and T3: 90 min after aortic clamp removal)

Figure 4

W/D of lung tissues (mean±SD). Changes of wet/dry (W/D) weight ratios of the two groups before and after CPB. The W/D weight ratio was calculated after placing the lung tissue at 85 °C for 72 hr. Data are expressed as the mean±SD, (n=5 per group). ##P<0.01, compared with the control group; *P<0.05, **P<0.01, compared with the T0 (T0: before CPB, T1: before aortic clamp removal, T2: 30 min after aortic clamp removal, and T3: 90 min after aortic clamp removal)

Figure 5

MPO activity of lung tissues (mean±SD). Changes of MPO activities in lung tissues of the two groups before and after CPB. Myeloperoxidase (MPO) levels were measured using colorimetry. Data are expressed as the mean±SD, (n=5 per group). ##P<0.01, compared with the control group; **P<0.01, compared with the T0 (T0: before CPB, T1: before aortic clamp removal, T2: 30 min after aortic clamp removal, and T3: 90 min after aortic clamp removal)