Submitted on March 10, 2003
Accepted on April 16, 2004
Vascular Transfer of Adenovirus is Augmented by Nitric Oxide in the Rat Heart
Alexander Sasse1, Zhaoping Ding1, Martina Wallich1, Axel Godecke1, and Juergen Schrader1*
1 Institut fuer Herz- und Kreislaufphysiologie, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
* To whom correspondence should be addressed. E-mail: Schrader{at}uni-duesseldorf.de.
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 the fluorescence dye rhodamine. 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 NO-Donors 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.
