Effects of linear polyethylenimine and polyethylenimine/DNA on lung function after airway instillation to rat lungs

Lung transplantation is an acceptable treatment option for various end-stag e pulmonary diseases, but long-term survival currently lags behind that aft er transplantation of other solid organs. We hypothesized that gene transfe r to grafts before transplantation may be a useful method to deliver antiox idant and/or anti-inflammatory genes to modulate these processes. For this purpose, we assessed the efficiency of gene transfer and effects on lung fu nction of the synthetic polycation, linear polyethylenimine (PEI), after ai rway instillation to the lungs of Fischer rats. Twenty-four hours after gen e delivery, reporter gene activity in DNA/PEI treated rats was approximatel y 12-fold higher than that in rats treated with naked DNA, but by 72 hours there was no significant difference between groups and activity had decreas ed by at least 85%. Function of the transfected left lung was assessed by m easuring arterial PaO2 levels and was found to be significantly lower at 24 and 72 hours after gene transfer in the PEI/DNA group compared with the na ked DNA group. The deterioration in lung function correlated with histologi cal findings. Rats treated with PEI alone and sacrificed after 72 hours sho wed an impairment in lung function similar to tha seen with PEI/DNA treatme nt. Our studies highlight the importance of assessing the functional capaci ty of a graft after gene transfer to determine suitability for subsequent t ransplantation.