A novel strategy of decoy transfection against nuclear factor-kappaB in myocardial preservation.
BACKGROUND
Nuclear factor-kappaB (NFkappaB) is critical for the transcription of multiple genes involved in myocardial ischemia-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 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 degrees 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 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 IL-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.
Department of Surgery, Course of Interventional Medicine, Osaka University Graduate School of Medicine, Japan.
T
T
Sakaguchi
Y
Y
Sawa
N
N
Fukushima
M
M
Nishimura
H
H
Ichikawa
Y
Y
Kaneda
H
H
Matsuda
D000818:Animals; D015316:Genetic Therapy; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics*; D009926:Organ Preservation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000502:physiology
D016328:NF-kappa B