Rapamycin-coated expanded polytetrafluoroethylene bypass grafts exhibit decreased anastomotic neointimal hyperplasia in a porcine model.

OBJECTIVE: We tested the hypothesis that rapamycin coated onto, and eluted from, expanded polytetrafluoroethylene (ePTFE) grafts would diminish neointimal hyperplasia in a porcine model. METHODS: Rapamycin (also called sirolimus) was coated onto the luminal surface of 6-mm-internal-diameter thin-walled ePTFE grafts by using an adhesive polymer that allows timed release of the drug. An adhesive polymer that allows timed release of rapamycin from ePTFE was developed with commercially available chemicals and applied on 6-mm ePTFE grafts. Graft integrity was characterized by scanning electron microscopy, and rapamycin levels were quantified by using high-performance liquid chromatography. Twenty-two mongrel pigs were randomized into three groups: untreated ePTFE (n = 6), adhesive-only coated ePTFE (n = 6), or adhesive- and rapamycin-coated ePTFE (n = 10). End-to-side unilateral aortoiliac bypasses were performed by using 6-mm-internal-diameter ePTFE grafts and standardized anastomotic lengths. Unilateral end-to-side aortoiliac ePTFE grafts (6-mm internal diameter) were inserted by using polypropylene sutures, 6-0 proximally and 7-0 distally; all anastomoses were 12 mm long. All animals received aspirin (325 mg orally) daily. All animals were given oral aspirin (325 mg) daily beginning on the day before surgery. At 28 days, the animals were killed, and the grafts were explanted in continuity with the adjacent aortic cuff and the outflow iliac artery. Variables compared between groups included graft patency, distal anastomotic length and cross-sectional narrowing, and intimal thickness at the arterial-graft junction indexed to the adjacent graft thickness. Microscopic analysis was performed with hematoxylin and eosin and Masson trichrome stains on paraffin sections. A pathologist blinded to experimental groups graded sections for collagen deposition, neointima formation, inflammatory cellular infiltrates, medial necrosis, and aneurysmal degeneration. RESULTS: All animals survived until they were killed without clinical evidence of limb ischemia or graft infection. Preplanned t tests in the context of one-way analysis of variance showed no difference in outcome measures between the untreated ePTFE and adhesive-only coated ePTFE groups; therefore, they were combined in further comparisons with the adhesive- and rapamycin-coated ePTFE group. The Rapamycine eluting expanded polytetrafluoroethylene group had longer anastomoses (85.6% vs 60.6% of the initial anastomotic length maintained; P < .0001) and less cross-sectional narrowing in the outflow graft (16.2% vs 28.5%; P = .0007) when compared with the other two groups by using two-tailed Student t tests. There was no evidence of medial necrosis or aneurysmal degeneration. All patent grafts had complete endothelialization on hematoxylin and eosin sections. Rapamycin was detectable and quantifiable in the arterial wall at 28 days after implantation. CONCLUSIONS: Rapamycin can be coated onto and eluted from ePTFE by using a nonionic polymer and a simple coating technique. At 4 weeks after implantation, the rapamycin-eluting ePTFE grafts demonstrate gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with non-drug-eluting ePTFE. Four weeks after implantation in a porcine model, rapamycin-eluting ePTFE grafts demonstrated gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with untreated and adhesive-only coated ePTFE grafts. CLINICAL RELEVANCE: Rapamycin-eluting ePTFE grafts decrease neointimal hyperplasia in a porcine model. Further studies are needed to evaluate whether patency will be improved. Rapamycin-eluting ePTFE grafts may allow the use of prosthetic grafts in situations in which autologous vein is unavailable and in which neointimal hyperplasia is pronounced, such as in small-diameter (<6-mm) vessels typical of infrapopliteal interventions.

Endovascular repair of the thoracic aorta: lessons learned.

BACKGROUND: Available information on outcome and best strategies for thoracic endovascular repair is somewhat limited and unclear. We sought to gain a better understanding of these issues through a retrospective review of our 8-year clinical experience in the treatment of thoracic aortic aneurysms and dissections. METHODS: A retrospective chart review of 186 patients undergoing stent-graft repair of thoracic aortic lesions at our institution during the 92-month period ending on December 31, 2004 was performed. Patients were divided into two groups based on the indication for treatment; group A had thoracic aortic aneurysms (TAA) and group B had type B aortic dissections (TBAD). Both groups were analyzed for outcome variables including technical success, mortality, major morbidity, endoleak rate and type, secondary endovascular interventions, and long-term survival. Mean follow-up was 40 months (range, 1 to 92 months). RESULTS: Compared to group B, group A patients were older and had a higher incidence of peripheral vascular disease and chronic obstructive pulmonary disease. Sixty percent of all patients were American Society of Anesthesiologists class III and the remainder were class IV (38.3%) and V (1.7%). The procedure was completed in 180 patients (96.7%), with all 6 failures being access-related. The average procedure time was 149 minutes (range, 72 to 405). The 30-day mortality was 4.7% (9 patients), and serious morbidity was 19.9% (37 patients). Eight patients (4.3%) developed spinal cord ischemia, 4 immediately after the procedure and 4 delayed (1 to 3 days). Total hospital length of stay averaged 6.7 days. Secondary endovascular interventions were successful in 17 patients with angiographically confirmed endoleaks (type I and III). At an average follow-up of 40 months, freedom from all-cause mortality was 62.5% in group A and 58.1% in group B. CONCLUSIONS: Stent-graft repair for TAA and TBAD can be achieved with high technical success and comparatively low rates of morbidity and mortality. Midterm survival appears to be favorable. Further refinements in device technology and procedural techniques are needed.

Idiopathic renal artery and infrarenal aortic aneurysms in a 6-year-old child: case report and literature review.

Multiple arterial aneurysms are distinctly rare in the pediatric population. Most arterial aneurysms in children are secondary to infections, trauma, arteritides, collagen vascular diseases, and other causes. True idiopathic aneurysms are the least common and less than a dozen reports of multiple idiopathic aneurysms have been published. We present a case of an idiopathic, symptomatic renal artery aneurysm with fistulization to the renal vein and a concomitant abdominal aortic aneurysm in a 6-year-old boy. The diagnostic workup, surgical treatment, pathologic findings, and a review of the literature are presented.