Recombinant adenoviral gene transfer does not affect cardiac allograft vasculopathy.
BACKGROUND
Adenovirus serotype 5 has remained the pre-eminent vector in pre-clinical gene therapy applications in cardiac transplantation. Concerns over the potential effects of adenoviral vectors on the later development of cardiac allograft vasculopathy (CAV) are addressed in this study.


METHODS
Hearts (n = 22) harvested from Brown Norway rats were perfused ex vivo with either University of Wisconsin (UW) solution with no virus, Ad-CMV-LacZ or Ad-CMV-Null. Donor hearts were transplanted heterotopically into the abdomen of Lewis rats. All recipients received cyclosporine for the duration of the experiment. Transplanted hearts were recovered for analysis at 120 days. Sections of the heart were stained with elastic-van Gieson stain for morphometric analysis of the vessels to ascertain the degree of vascular luminal occlusion. Hematoxylin-eosin staining facilitated diagnosis of chronic rejection.


RESULTS
Seventy-seven percent of transplanted hearts showed signs of chronic rejection with no difference in the proportion of animals between groups (p = 0.797). No difference was noted in the degree of vascular luminal occlusion between the Ad-Null (0.57 +/- 0.22), Ad-LacZ (0.62 +/- 0.19) and UW (0.47 +/- 0.29) groups (p = 0.653).


CONCLUSIONS
Vascularized cardiac allografts transplanted from Brown Norway to Lewis rats demonstrated cardiac allograft vasculopathy CAV at 120 days. Adenoviral perfusion of the donor heart ex vivo did not affect the development of CAV.
Rao
Vinay P
VP
William J. von Liebig Transplant Center, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Branzoli
Stefano E
SE
Ricci
Davide
D
Miyagi
Naoto
N
O'Brien
Timothy
T
Tazelaar
Henry D
HD
Russell
Stephen J
SJ
McGregor
Christopher G A
CG
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013997:Time Factors; D014652:Vascular Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*
D007166:Immunosuppressive Agents; D016572:Cyclosporine