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Am J Physiol Heart Circ Physiol 287: H1362-H1368, 2004. First published May 6, 2004; doi:10.1152/ajpheart.00193.2003
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Vascular transfer of adenovirus is augmented by nitric oxide in the rat heart

Alexander Sasse, Zhaoping Ding, Martina Wallich, Axel Gödecke, and Jürgen Schrader

Institut für Herz und Kreislaufphysiologie, Heinrich Heine University, 40225 Duesseldorf, Germany

Submitted 26 January 2003 ; accepted in final form 16 April 2004

Reversible opening of the endothelial barrier remains a major obstacle when hearts are transfected via the coronary system. Our aim was to establish an experimental system permitting the continuous analysis of vascular transfer of virus in the intact heart. Isolated saline-perfused rat hearts were inverted and covered with a latex cap to collect interstitial transudate (IT) on the pericardial surface. Adenovirus (109 pfu/ml) was stably labeled with rhodamine fluorescent dye. Analysis of IT and coronary perfusate revealed that under baseline conditions, adenovirus in the IT reached 75% of its vascular concentration within 3 min. The nitric oxide-donors S-nitroso-N-acetyl penicillamine (SNAP) and bradykinin (BK) were the most effective substances to increase total IT volume and adenoviral interstitial concentration. Perfusion with 9% serum markedly reduced IT volume flow and delayed the SNAP/BK effect. Our findings demonstrate that SNAP and BK effectively increased coronary transfer of adenovirus suggesting that the inverted isolated heart is a suitable model to optimize vascular transfer of virus under standardized conditions.

endothelial permeability; transvascular and transcoronary gene transfer; S-nitroso-N-acetyl penicillamine; interstitial transudate



Address for reprint requests and other correspondence: J. Schrader, Institut für Herz- und Kreislaufphysiologie, Heinrich-Heine-Univ. Duesseldorf, Germany, Universitaetsstr. 1, 40225 Duesseldorf, Germany (E-mail: Schrader{at}uni-duesseldorf.de).







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