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FIG 41.20 Movat pentachrome staining of the arterial duct (×400 magnification) Upper right panel shows the spontaneously contracted duct in 7-day-old piglet Upper left panel shows the duct, stented with a bare metal stent and immediately harvested Lower panels show examples of stented ducts representative of the bare and drug-eluting stent groups Note that there is negligible difference in lumen patency between the drugeluting stent and bare metal stent at 2 weeks but increased luminal compromise in the bare metal stent group at 4 and 6 weeks compared with the drug-eluting stent Bioengineering of the Arterial Duct for Therapeutic Gain Novel methodology is emerging for maintaining ductal patency into the postnatal period to sustain life and allow surgical intervention of duct-dependent cardiac malformations Maintenance of ductal patency has been described through surgical transfection of fetal lambs219; by targeting the ductal smooth muscle cells with an expression vector encoding a “decoy” mRNA of the fibronectin message, it proved possible to sequester the protein it binds, thereby preventing upregulation of fibronectin and arresting intimal cushions This approach emphasizes both the importance of fibronectin to the process of ductal closure and identifies a new therapeutic modality and target Although fetal surgery is likely not feasible in the clinical setting, an alternative approach of targeting chemotherapeutic agents given by systemic infusion to different vascular beds by unique peptide “zip codes” may offer bright therapeutic avenues.220 Humpl and colleagues investigated percutaneous postnatal transfection of a vector containing the gene for prostaglandin into ductal tissue, resulting in prolonged patency.221 These studies identifying and characterizing the cellular and molecular mechanisms involved in ductal patency and closure have advanced our understanding of this developmentally programmed fetal vessel The impact of these advances extends beyond the scope of ductal remodeling because they have provided insight into the pathogenesis of occlusive vascular diseases, processes that use similar pathways This work has also positioned the field toward further advances associated with the development of safe therapeutic measures to maintain ductal patency for infants with cyanotic congenital heart disease, ultimately translating into improved care and clinical outcome Annotated References Gross RE, Hubbard JP Surgical ligation of a patent ductus arteriosus A report of first successful case JAMA 1939;112:729–731 This landmark report ushered in the era of corrective surgery for congenital heart lesions An interesting irony, that it was management of the arterial duct by transcatheter approaches that also established minimally invasive management of congenital heart lesions Tynan M The murmur of the persistently patent arterial duct, or “the colonel is going to a dance” Cardiol Young 2003;13:559–562 Dr Tynan reminds us of the history of the clinical recognition of the arterial duct by Gibson and the importance of confirming our sources Coceani F, Olley PM The response of the ductus arteriosus to prostaglandins Can J Physiol Pharmacol 1973;51:220–225 This landmark paper was first to describe the actions of prostaglandins on the arterial duct Although the original hypothesis was that prostaglandin leads to ductal constriction, these investigators experimental findings became the underpinning for the understanding of the