Abstract
In congenital heart disease with left- or right-sided obstruction, prostaglandin E (PGE)1 or PGE2 is infused to maintain ductus arteriosus (DA) patency. We hypothesized that transfection of the DA with PGE synthase would lead to a greater production of PGE2 in situ and, hence, patency of the DA. The cDNA for human prostaglandin synthase was sequenced and ligated into a eukaryotic expression vector. The negative control was created by ligating the cDNA encoding the bacterial protein chloramphenicol acetyltransferase into the same plasmid. Transfection (600 μg DNA) was achieved in lambs within the first 24 h of life using the hemagglutinating virus of Japan (HVJ)-liposome transfection method with a custom-made, basket-weave-perforated catheter. Echocardiography was performed to assess DA patency until the time of sacrifice. To confirm expression of the transgene, PGE2 concentration was measured in organ culture of the DA by immunoassay and by Western immunoblotting of homogenized DA tissue. Patency of the DA was demonstrated by color Doppler in all the lambs (7/7) in which the PGE synthase was delivered, whereas functional closure was seen in the control group (6/6). The PGE2 concentration in the culture medium of the explanted DA in the treatment group was 3-fold higher than that of the control groups. Western immunoblotting confirmed the presence of PGE synthase in the treatment group. Gene transfer of PGE synthase to the DA is feasible and will maintain patency for at least 1 wk.
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Abbreviations
- CAT:
-
chloramphenicol acetyltransferase
- DA:
-
ductus arteriosus
- ET-1:
-
endothelin-1
- HVJ:
-
hemagglutinating virus of Japan
- PGE2:
-
prostaglandin E2
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Acknowledgements
The authors thank Cameron Slorach, Echo Technologist, Hospital for Sick Children, Toronto, Ontario, Canada, for technical assistance during echocardiography of the animals.
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Supported by a grant from the Canadian Institutes of Health Research MT723 and from the Martin Foundation through the Hospital for Sick Children Foundation. M.R. is an endowed chair of the Heart and Stroke Foundation of Ontario and a Distinguished Scientist of the Canadian Institutes of Health Research MT 723.
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Humpl, T., Zaidi, S., Coe, J. et al. Gene Transfer of Prostaglandin Synthase Maintains Patency of the Newborn Lamb Arterial Duct. Pediatr Res 58, 976–980 (2005). https://doi.org/10.1203/01.PDR.0000182820.20333.2A
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DOI: https://doi.org/10.1203/01.PDR.0000182820.20333.2A
