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Ann Thorac Surg 2002;73:432-437
© 2002 The Society of Thoracic Surgeons

Original article: general thoracic

Non-viral gene delivery to atelectatic and ventilated lungs

Uz Stammberger, MDa, Aima N. Uduehi, PhDa, Bartosz Kubisa, MDa, Thierry Roth, MDa, Ralph A. Schmid, MD*a

a Division of General Thoracic Surgery, University Hospital, Berne, Switzerland

* Address reprint requests to Dr Schmid, Division of General Thoracic Surgery, University Hospital, CH-3010 Berne, Switzerland
e-mail: ralph.schmid{at}insel.ch

Presented at the Thirty-seventh Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 29–31, 2001.

Background. Three different nonviral vectors and naked DNA were evaluated for in vivo transfer of plasmid DNA to rat lungs through airways in either atelectatic or ventilated lungs.

Methods. The F344 rats underwent instillation of 300 µg DNA (pCIluc, luciferase) to the left lung. Naked DNA, linear polyethylenimine, branched polyethylenimine, and lipid GL-67 (in either atelectatic or ventilated lungs) were assessed (n = 5 per group). After 24 hours, left lung PaO2 (mm Hg) and luciferase activity (RLU/mg) were measured. The median (range) was given, and the analysis of variance was applied, followed by the planned comparison on log-transformed data.

Results. In atelectatic lungs, lipid GL-67 was best (927 [330 to 4112] RLU/mg; p < 0.001 versus other groups of atelectatic lung; p < 0.001 versus all other groups), but highest luciferase activity in all groups was measured in ventilated lungs using linear polyethylenimine (1,240 [922 to 2519] RLU/mg; p < 0.001 versus other groups of ventilated lung; p < 0.001 versus all other groups). In comparison with naked DNA, all nonviral vector systems significantly impaired PaO2 24 hours after airway transfection (p < 0.001; naked DNA versus all other groups). Regardless of transfection technique, PaO2 was worst in lungs transfected by linear polyethylenimine.

Conclusions. Highest transfection was achieved with GL-67 in atelectatic lungs and with linear polyethylenimine in ventilated lungs. All gene delivery systems impaired gas exchange of the transduced lung in comparison with naked DNA.






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