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Eur J Cardiothorac Surg 2004;26:960-967
© 2004 Elsevier Science NL

Adenovirus-mediated overexpression of inhibitor kappa B-alpha attenuates postinfarct remodeling in the rat heart

^a Ludwig Boltzmann Institute for Cardiosurgical Research, Medical University of Vienna, Vienna, Austria
^b Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
^c Department of Pathology, Medical University of Vienna, Vienna, Austria
^d Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria
^e Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria

Received 3 November 2003; received in revised form 14 July 2004; accepted 16 July 2004.

^* Corresponding authors. Address: Ludwig Boltzmann Institute for Cardiosurgical Research, c/o Institute of Biomedical Research, Medical University of Vienna, AKH-Wein, Währinger Gürtel 18-20, 1090 Vienna, Austria. Tel.: +43-1-40400-5221; fax: +43-1-40400-5229. (E-mail: b.k.podesser{at}cardiovascular-research.at).

Objective: The transcription factor nuclear factor kappa B (NF-kB) plays an important role in the inflammatory response following myocardial infarction. We hypothesized that NF-kB-blockade in an animal model of acute ischemia reduces the inflammatory response and therefore attenuates ventricular remodeling. Methods: Myocardial infarcts (MI) were produced in male Sprague–Dawley rats by ligation of the LAD and followed by adenovirus-mediated intramyocardial delivery of inhibitor kappa B-gene (n=10), the physiological inhibitor of the transcription factor nuclear factor kappa B, respectively, of a ß-gal reporter-gene (n=11). Sham-operated animals (n=10) received neither ligation nor gene transfer. Five days after MI IkB-expression levels were determined by western blotting. Seven weeks after MI in vivo cardiac function was evaluated by transthoracic echocardiography. Based on left ventricular endsystolic and enddiastolic diameters ejection fraction and fractional shortening were calculated. Only animals with MI involving more than 30% of the left ventricle were included. Data are given as mean±SD. Results: In IkB-transfected hearts IkB-levels were six-fold higher (P<0.05) than in ß-gal transfected hearts. Concerning in vivo hemodynamics IkB-treated hearts showed reduced systolic and diastolic left ventricular dimensions compared to the ß-gal MI-group (systolic 48±4 vs. 66±3mm; diastolic 67±5 vs. 84±6mm; P<0.01). Consequently fractional shortening (27.8±1.5 vs. 20.4±4.0%; P<0.01) and ejection fraction (63.4±3.6 vs. 49.1±8.3%; P<0.05) were preserved in IkB hearts compared to ß-gal MI-hearts. Conclusion: It can be concluded that overexpression of IkB leads to an improved cardiac function thereby attenuating postinfarct remodeling.

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