ESTABLISHMENT OF NEW IMMUNOSUPPRESSIVE STRATEGY USING GENE TRANSFECTION TECHNIQUE

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BACKGROUND : Nuclear factor-kappaB (NFkappaB) is critical for the transcription of multiple genes involved in myocardial ischernia-reperfusion injury. Therefore, we hypothesized that blocking NFkappaB 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 NFkappaB (NFkappaB decoy group) or a "rambled decoy group were transfected into rat hearts using a hemagglutinating virus ofjapan-liposome method. After 16 "urs of preservation in Euro-Collins solution at 4 degrees C, the cardiac grafts were heterotopically transplanted into recipient rats of the same strain. RESULTS: Fluorescein isothiocyanatestaining showed introduction of double-stranded oligonucleotides into the nuclei of endothelial cells and cardiomyocytes. After 1 hour of reperfusion the NFkappaB 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 1L-8, and neutrophil infiltration than did the scrambled decoy group (p < 0.05). CONCLUSIONS : Gene transfection of the NFkappaB decoy attenuates ischemia-reperfusion injury after prolonged heart preservation. As a result, this method appears to be a novel strategy for enhanced myocardial preservation.