Intrapericardial administration of adenovirus for gene transfer. Lamping, Kathryn G., C. David Rios, Jon A. Chun, Hiroaki Ooboshi, Beverly L. Davidson, Donald D. Heistad. Departments of Internal Medicine, Physiology, and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine and Veterans Administration Medical Center, Iowa City, Iowa 52242
APStracts 3:0325H, 1996.
Gene transfer to the heart has been accomplished with intravascular administration of adenoviral vectors. We hypothesized that administration of adenoviral vectors into the pericardial sac, by increasing duration of exposure to adenovirus, would result in gene expression in pericardium and perhaps myocardium, and therefore might provide an alternative method to intravascular administration for gene transfer. We injected replication-deficient adenovirus (average 1 x 1012 particles/ml in 3% sucrose; 1x1010 pfu/ml) containing cDNA encoding a nuclear-targeted bacterial -galactosidase into the pericardial sac of dogs. Samples of pericardium and heart were examined for enzymatic activity of -galactosidase and after histochemical staining with 5-bromo-4-chloro-3-indolyl- -D -galactopyranoside. One day after injection of adenovirus (1-3 ml), -galactosidase activity was highest in parietal pericardium and left atrial tissue, and lower in right and left ventricles. Histochemical expression of transgene was predominantly in visceral pericardium of atria and ventricles, and occasionally in epicardial myocytes, arterioles and venules. Pretreatment with doxycycline (5 mg) prior to adenovirus increased transgene activity in left ventricles. Thus, adenovirus injected into the pericardial sac provides an effective method for gene transfer to the visceral and parietal pericardium over atria and ventricles. 

Received 10 June 1996; accepted in final form 17 July 1996.
APS Manuscript Number H510-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996