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Ann Thorac Surg 2001;71:624-629
© 2001 The Society of Thoracic Surgeons


Original article: cardiovascular

A novel strategy of decoy transfection against nuclear factor-{kappa}B in myocardial preservation

Taichi Sakaguchi, MDa, Yoshiki Sawa, MDa, Norihide Fukushima, MDa, Motonobu Nishimura, MDa, Hajime Ichikawa, MDa, Yasufumi Kaneda, MDb, Hikaru Matsuda, MDa

a Department of Surgery, Course of Interventional Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
b Division of Gene Therapy Science, Osaka University Graduate School of Medicine, Osaka, Japan

Accepted for publication May 10, 2000.

Address reprint requests to Dr Sawa, Department of Surgery, Course of Interventional Medicine (E1), Osaka University Graduate School of Medicine, Yamada-oka 2-2, Suita, Osaka 565-0871, Japan
e-mail: sawa{at}surg1.med.osaka-u.ac.jp

Background. Nuclear factor-{kappa}B (NF{kappa}B) is critical for the transcription of multiple genes involved in myocardial ischemia-reperfusion injury. Therefore, we hypothesized that blocking NF{kappa}B would attenuate ischemia-reperfusion injury after prolonged myocardial preservation, resulting in an improvement in cardiac function.

Methods. Double-stranded oligodeoxynucleotides with a specific affinity for NF{kappa}B (NF{kappa}B decoy group) or a scrambled decoy group were transfected into rat hearts using a hemagglutinating virus of Japan–liposome method. After 16 hours of preservation in Euro-Collins solution at 4°C, the cardiac grafts were heterotopically transplanted into recipient rats of the same strain.

Results. Fluorescein isothiocyanate staining showed introduction of double-stranded oligonucleotides into the nuclei of endothelial cells and cardiomyocytes. After 1 hour of reperfusion the NF{kappa}B decoy group showed significantly higher degrees of recovery of left ventricular function as well as significantly lower levels of serum creatine phosphokinase, myocardial water content, tissue IL-8, and neutrophil infiltration than did the scrambled decoy group (p < 0.05).

Conclusions. Gene transfection of the NF{kappa}B decoy attenuates ischemia-reperfusion injury after prolonged heart preservation. As a result, this method appears to be a novel strategy for enhanced myocardial preservation.


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Baiya Krishnadasan and Edward D. Verrier
Ann. Thorac. Surg. 2001 71: 629-630. [Extract] [Full Text] [PDF]



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