Electroporation-mediated gene delivery of na+,k+-atpase, and enac subunits to the lung attenuates acute respiratory distress syndrome in a two-hit porcine model

Bryanna M. Emr, Shreyas Roy, Michaela Kollisch-Singule, Louis A. Gatto, Michael Barravecchia, Xin Lin, Jennifer L. Young, Guirong Wang, Jiao Liu, Joshua Satalin, Kathleen Snyder, Gary F. Nieman, David A. Dean

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Introduction: Acute respiratory distress syndrome (ARDS) is a common cause of organ failure with an associated mortality rate of 40%. The initiating event is disruption of alveolar-capillary interface causing leakage of edema into alveoli. Hypothesis: Electroporation-mediated gene delivery of epithelial sodium channel (ENaC) and Na+,K+-ATPase into alveolar cells would improve alveolar clearance of edema and attenuate ARDS. Methods: Pigs were anesthetized and instrumented, and the superior mesenteric artery was clamped to cause gut ischemia/reperfusion injury and peritoneal sepsis by fecal clot implantation. Animals were ventilated according to ARDSnet protocol. Four hours after injury, animals were randomized into groups: (i) treatment: Na+,K+-ATPase/ENaC plasmid (n = 5) and (ii) control: empty plasmid (n = 5). Plasmids were delivered to the lung using bronchoscope. Electroporation was delivered using eight-square-wave electric pulses across the chest. Following electroporation, pigs were monitored 48 h. Results: The PaO2/FIO2 ratio and lung compliance were higher in the treatment group. Lung wet/dry ratio was lower in the treatment group. Relative expression of the Na+,K+-ATPase transgene was higher throughout lungs receiving treatment plasmids. Quantitative histopathology revealed a reduction in intra-alveolar fibrin in the treatment group. Bronchoalveolar lavage showed increased surfactant protein B in the treatment group. Survival was improved in the treatment group. Conclusions: Electroporation-mediated transfer of Na+,K+-ATPase/ENaC plasmids improved lung function, reduced fibrin deposits, decreased lung edema, and improved survival in a translational porcine model of ARDS. Gene therapy can attenuate ARDS pathophysiology in a highfidelity animal model, suggesting a potential new therapy for patients.

Original languageEnglish (US)
Pages (from-to)16-23
Number of pages8
Issue number1
StatePublished - 2015

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine


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