No abstract

Percutaneous transluminal angioplasty has been shown to be both feasible and efficacious for the treatment of aortic coarctation. Recent reports, however, have indicated that the development of aortic aneurysms at or near the coarctation segment may complicate attempts to treat this lesion by catheter-based intervention. Accordingly, we examined the light microscopic features of coarctation segments excised at surgery (n = 31) or obtained at autopsy (n = 2) in 33 patients with coarctation of the aorta. Cystic medial necrosis, defined as depletion and disarray of elastic tissue, was observed in each of the 33 specimens. In the majority of coarctation specimens (22 of 33 or 67%) the extent of cystic medial necrosis, graded semiquantitatively on a scale of 0 (normal aorta) to 3 +, was severe (3 + ). The finding that cystic medial necrosis represents a consistent histologic feature of coarctation of the aorta provides a pathologic basis for the formation of aneurysms observed after balloon angioplasty of coarctation sites.Circulation 75, No. 4, [689][690][691][692][693][694][695] 1987. SINCE Gruintzig's successful development of percutaneous transluminal coronary angioplasty,l catheterbased interventional techniques have been applied to an increasingly wider assortment of cardiovascular disorders. Preliminary trials of pulmonary,2 mitral,3 and aortic4 balloon valvuloplasty have yielded encouraging results. While the initial experience with balloon dilation for coarctation of the aorta was reported to be similarly favorable,5-9 recent postangioplasty followup studies in such patients have indicated that aneurysm formation at or near the coarctation segment may be a consequence of this intervention.'0' 11 Several lines of evidence have strongly suggested that aneurysm formation after coarctation angioplasty might be related to underlying aortic histopathology. First, cystic medial necrosis has been observed as a predictable consequence of aortic banding in a canine preparation of cardiac hypertrophy.'2 Second, before

(1) Efficient, adenovirus-mediated, arterial gene transfer to endothelial and/or smooth muscle cells is feasible by percutaneous, clinically applicable techniques. (2) Consistent transfection of medial smooth muscle cells may be achieved when the endothelial layer is abraded. (3) Medial transfection is more efficient when an HBC, rather than a DBC, is used. (4) Percutaneous delivery of the adenoviral vector via HBC results in site-specific arterial gene transfer. Very-low-level extra-arterial transfection may occur, however, when the DBC is used.

Percutaneous adenovirus delivery of the gax gene to rabbit iliac arteries following endothelial denudation and vessel wall injury reduces neointimal hyperplasia and luminal stenosis, but does not affect endothelium-dependent vasomotion. This study demonstrates that a VSMC transcription factor can potentially be utilized for the development of a molecular therapy for vascular disorders.