Balloon angioplasty with stent implantation in experimental coarctation of the aorta.

BACKGROUND: Balloon angioplasty of coarctation of the aorta is an effective method of treatment but is complicated by tearing of the aortic intima, formation of aneurysms, and restenosis. Stent placement at the time of balloon dilation could prevent restenosis and could also prevent progression of intimal tears to aneurysms. The purpose of this study was to evaluate the feasibility of balloon dilation and implantation of balloon-expandable stents in an experimental model of coarctation and to examine the effect of stent placement at the site of surgically created stenosis. METHODS AND RESULTS: Coarctation of the aorta was surgically produced in 11 juvenile swine. Simultaneous coarctation angioplasty and stent implantation was performed in 10 animals 34 +/- 7.8 days after surgery. Repeat catheterization was performed 59 +/- 6 days after stent implantation. Five animals underwent reexpansion of stents with subsequent follow-up catheterization. Aortic specimens were examined by light microscopy and scanning electron microscopy. Coarctation angioplasty with stent implantation was successful in all, with an increase in coarctation diameter from 46 +/- 8.5% to 90 +/- 12.2% of proximal aortic diameter (P = .0001). Systolic pressure gradient decreased from 32 +/- 19.8 to 0.5 +/- 2.8 mm Hg (P < .001). All stents were patent at follow-up catheterization, with no evidence of intraluminal thrombosis. Reexpansion in five animals increased the stent diameter from a mean of 77.4 +/- 12.1% to 93 +/- 11.0% of proximal aortic diameter (P = .02). Gross examination of aortic specimens demonstrated formation of neointima over the stent wherever the stent struts were in contact with the aortic wall. The stent occupied a subintimal position and produced minimal compression of the underlying media. Medial compression was noted immediately beneath stent struts, but there was no evidence of intimal or medial dissection. CONCLUSIONS: Balloon angioplasty with simultaneous implantation of balloon-expandable stents is effective in relieving aortic obstruction in experimental coarctation. Reexpansion of the rigid stent can be performed in an area of surgical aortotomy and coarctation without significant intimal or medial injury. Stent implantation may be useful in preventing restenosis and aneurysm formation after angioplasty of coarctation.

Re-expansion of balloon-expandable stents after growth.

OBJECTIVES: The purpose of this study was to evaluate the feasibility of re-expansion of balloon expandable intravascular stents and to examine the gross and histologic effects of re-expansion on vascular integrity. BACKGROUND: Intravascular stents have been used successfully as an adjunct to balloon dilation of congenital pulmonary artery branch stenosis and postoperative stenosis of the pulmonary arteries in children. However, use of rigid stents in children could result in development of relative stenosis at the site of stent implantation with subsequent growth of the child. METHODS: Stainless steel "iliac" stents were placed in the thoracic aorta of 10 normal juvenile swine by a transcatheter technique. Angiography and re-expansion were performed at a mean of 11 weeks (n = 9) and again at 18 weeks (n = 5). After euthanasia, the aortic specimens were removed for gross and histologic examination. RESULTS: Stents were successfully implanted in 10 swine. Re-expansion was successfully performed in each animal at 11 weeks and at 18 weeks. Aortic growth produced a relative constriction of the aorta of 20% +/- 10% (mean +/- SD) at the site of stent implantation at both 11 and 18 weeks. Re-expansion produced a significant increase in mean stent diameter from 10.1 +/- 1 mm to 12.3 +/- 1.2 mm at 11 weeks and from 11.2 +/- 0.7 to 13.5 +/- 1.1 mm at 18 weeks after implantation (p < 0.001). Balloon dilation produced a relative increase in stent diameter of 21% +/- 7% at 11 weeks and 18% +/- 4% at 18 weeks. Stent re-expansion was accompanied by plastic deformation of the neointima without neointimal dissection. Where neointima was thick, there was no evidence of neointimal abrasion, but where neointima was thin, areas of localized neointimal abrasion were observed with focal fibrin and platelet adherence to the stent struts. There was no evidence of medial or adventitial hemorrhage or dissection produced by re-expansion. CONCLUSIONS: Re-expansion of intravascular stents is feasible after growth in juvenile swine without significant injury to neointima, media or adventitia. The results of this study support careful and selective use of intravascular stents as an adjunct to balloon dilation of congenital stenoses in children.

Melphalan-induced toxicity in nude mice following pretreatment with buthionine sulfoximine.

Melphalan-induced toxicity in nude mice following pretreatment with a regimen of L-buthionine sulfoximine (BSO), previously shown to enhance the activity of this alkylating agent against rhabdomyosarcoma and glioma xenografts, was examined. Mice were pretreated with i.p. BSO (2.5 mmol/kg x 7 doses at 12-h intervals plus concomitant availability of a 20-mM solution in the drinking water) or vehicle prior to a single i.p. injection of melphalan (35.65 mg/m2). As compared with control animals who received no BSO pretreatment, mice pretreated with BSO lost weight prior to therapy with melphalan (6.9% weight loss vs 0.3% weight gain; P less than 0.005) and showed a greater mean nadir weight loss after melphalan (3.8% vs. 2.1%; P = 0.049). Treatment with melphalan was associated with histologic evidence of reversible gastrointestinal toxicity, reversible myelosuppression, and histologic evidence of acute renal tubular necrosis, with no differences being observed between mice that had been pretreated with BSO and those that had been pretreated with vehicle. No evidence of cardiac, hepatic, or skeletal muscle toxicity was found in melphalan-treated animals. These results suggest that treatment of nude mice with melphalan following BSO-mediated depletion of glutathione does not result in enhanced organ toxicity despite an increase in the antineoplastic activity of this alkylating agent.