Ventilator-induced lung injury (VILI) promotes ischemia/reperfusion lung injury (I/R) and NF-kB antibody attenuates both injuries

SummaryRationaleWhether the ventilator-induced lung injury (VILI) superimposed on ischemia/reperfusion injury (I/R) causes synergistic damage has not been well explored. Whether nuclear factor-kappa B (NF-kB) antibody has protective effects for both injuries is also unknown.MethodsI/R and VILI were produced in an isolated rat lung model. Hemodynamics, lung weight gain (LWG), capillary filtration coefficient (Kfc), cytokines, and lung pathology were assessed.ResultsVILI or I/R produced similar permeability pulmonary edema which was reflected by increasing Kfc and LWG. Cytokine (IL-1β) up-regulation occurred in both injuries. Pathologic examination showed edema and inflammatory cell infiltration in VILI or I/R. In addition, the alveoli were overdistended and even ruptured because of marked inhomogeneity of inflation in VILI. Furthermore, combined I/R and VILI produced further increases in Kfc, LWG, IL-1β, as well as more severe pathologic changes. Conversely, less permeability pulmonary edema, pathologic changes and IL-1 expression were found in groups pretreated with anti-NF-kB antibody.ConclusionVILI and I/R cause synergistic damage on the lung. I/R or VILI alone or combined can be attenuated by NF-kB antibody. NF-kB plays an important role in both forms of lung injury. We propose anti-NF-kB antibody pretreatment to be beneficial for VILI, I/R and lung transplantation.