Ventilator-induced lung injury (VILI) promotes ischemia/reperfusion lung injury (I/R) and NF-kappaB antibody attenuates both injuries.
BACKGROUND
Whether 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-kappaB) antibody has protective effects for both injuries is also unknown.


METHODS
I/R and VILI were produced in an isolated rat lung model. Hemodynamics, lung weight gain (LWG), capillary filtration coefficient (K(fc)), cytokines, and lung pathology were assessed.


RESULTS
VILI or I/R produced similar permeability pulmonary edema which was reflected by increasing K(fc) and LWG. Cytokine (IL-1beta) 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 K(fc), LWG, IL-1beta, 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-kappaB antibody.


CONCLUSIONS
VILI and I/R cause synergistic damage on the lung. I/R or VILI alone or combined can be attenuated by NF-kappaB antibody. NF-kappaB plays an important role in both forms of lung injury. We propose anti-NF-kappaB antibody pretreatment to be beneficial for VILI, I/R and lung transplantation.
Chiang
Chi-Huei
CH
Institute of Emergency and Critical Care Medicine, Medical School, National Yang-Ming University, Taipei, Taiwan. chiang01@vghtpe.gov.tw
Pai
Hsin-I
HI
Liu
Shiou-Ling
SL
D000704:Analysis of Variance; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D006439:Hemodynamics / Q000187:drug effects; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D014655:Vascular Resistance; D055397:Ventilator-Induced Lung Injury / Q000188:drug therapy* / Q000503:physiopathology
D007375:Interleukin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha