MAHOROBA, first-in-man study: 6-month results of a biodegradable polymer sustained release tacrolimus-eluting stent in de novo coronary stenoses.

AIMS: To report the 4-month angiographic and 6-month clinical follow-up in first-in-man study using the tacrolimus-eluting bioabsorbable polymer-coated cobalt-chromium MAHOROBA stent. METHODS AND RESULTS: A total of 47 patients with either stable angina or unstable angina, or silent myocardial ischaemia, based on a de novo coronary stenosis that could be covered by a single 18 mm stent in a native coronary artery with a diameter between 3.0 and 3.5 mm were enrolled at three sites. The primary endpoint was in-stent late loss at 4 months. The secondary endpoints include %volume obstruction of the stents assessed by intravascular ultrasound (IVUS) at 4 months and major adverse cardiac events (MACE) at 6 months. Forty-seven patients were enrolled. Procedural success was achieved in 97.9%. At 4-month follow-up, in-stent late loss was 0.99 +/- 0.46 mm, whereas in-stent %volume obstruction in IVUS was 34.8 +/- 15.8%. At 6 months, there were no deaths, but 2 patients suffered from a myocardial infarction and 11 patients required ischaemia-driven repeat revascularization. The composite MACE rate was 23.4%. CONCLUSION: This tacrolimus-eluting stent failed to prevent neointimal hyperplasia, despite the theoretical advantages of the tacrolimus, which has less inhibitory effects on endothelial cells than smooth muscle cells.

Immobilization of basic fibroblast growth factor on a platinum microcoil to enhance tissue organization in intracranial aneurysms.

OBJECT: To enhance tissue organization in an aneurysm lumen, the authors prepared a platinum microcoil carrying basic fibroblast growth factor (bFGF) and analyzed its effectiveness in the treatment of aneurysms. METHODS: Ultrathin multiorganic layers were assembled on a platinum coil through successive deposition of cationic polyethylenimine and anionic heparin, and then bFGF was immobilized through an affinity interaction with heparin. The bFGF was effectively immobilized on the surface of the platinum coil without deterioration of the coil's mechanical properties. Coil embolization of aneurysms constructed using a canine common carotid artery was performed via the endovascular approach. The aneurysms together with parent arteries were harvested 2 weeks after coil embolization. Platinum coils unmodified, coated with heparin, or immobilized with heparin and bFGF were examined. The percentage of occlusion at the aneurysm orifice in animals treated with bFGF-immobilized coils (92.99+/-7.94%) was significantly greater than that in animals treated with heparin-coated coils (57.26+/-10.76%) or unmodified coils (52.86+/-8.54%). The histological score of the aneurysms treated with bFGF-immobilized coils was also significantly greater than the scores in the control group. CONCLUSIONS: These results indicated that bFGF-immobilized microcoils may be beneficial in the obliteration of aneurysms.

Vascular endothelial growth factor immobilized on platinum microcoils for the treatment of intracranial aneurysms: experimental rat model study.

Platinum microcoils coated with immobilized recombinant human vascular endothelial growth factor (rhVEGF) were prepared and the effectiveness for the embolization of aneurysms was investigated using a rat model. Platinum coils were prepared by successive deposition of cationic polyethyleneimine and anionic heparin, and VEGF was immobilized through affinity interaction with heparin. Unmodified, heparin-coated, or rhVEGF-immobilized platinum coil segments were inserted into the ligated external carotid arteries at the bifurcation of the common carotid artery (CCA) of adult female rats. The bifurcation segments of the CCA were harvested 2 weeks after the coil placement. rhVEGF-immobilized coils showed significantly greater endothelial formation at the aneurysm orifice and cell infiltration in the aneurysm body compared with the unmodified and heparin-coated coils. The percentage of sac occlusion was significantly greater in the rhVEGF-immobilized group (77.53 +/- 27.58%) than in the heparin-coated group (44.81 +/- 38.30%) and unmodified group (34.99 +/- 28.15%). Scanning electron microscopy showed a tendency for more fibrotic and cellular collections on the coil surface and more tissue mass filling in the coil lumen in the rhVEGF-immobilized group. Platinum microcoils coated with immobilized rhVEGF may be effective for the obliteration of aneurysms.

Development of gold stents for the treatment of intracranial aneurysms: an experimental study in a canine model.

BACKGROUND AND PURPOSE: Gold has often been used in medicine because of its radiopacity and flexibility. To perform stent-supported coil embolization of intracranial aneurysms, we prepared a gold stent and examined its flexibility, radiopacity, and thrombogenic properties in comparison with a stainless steel device implanted in vitro and in vivo. METHODS: Gold stents were prepared by plating gold on stainless steel stents as a template. Their mechanical properties and trackability in vitro were determined and compared with those of stainless steel stents of the same design. Twenty gold stents and two stainless steel stents were implanted in canine external carotid, vertebral, and renal arteries, as a muscle branch of the maxillary arteries, to examine their performance in vivo. RESULTS: The gold stent exhibited much less radial force and greater flexibility than the stainless steel stent. It also demonstrated superior trackability and radiopacity in the experimental endovascular procedures in canines. Histologic examination showed good patency of the stented artery with slight endothelial hypertrophy. CONCLUSION: Although there is still room for more radial strength, less influence on intimal hypertrophy, a more suitable flexibility, and a smoother surface, the superior trackability and radiopacity of gold stents seem to support use of this device for the endovascular treatment of intracranial aneurysms.

In vitro evaluation of newly developed adsorbent for selective removal of glycosylated low-density lipoprotein.

Chronic hyperglycemia leads to the accumulation of nonenzymatically derived glycosylation products on proteins. Such glycosylation products, especially glycosylated low-density lipoprotein (glc-LDL), have been increasingly recognized as factors in the pathogeneses of diabetic complications. A new adsorbent was developed for the selective removal of glc-LDL from plasma. The adsorbent has dual ligands in order to improve the specific binding affinity for glc-LDL that consisted of boronic acid moiety for the glycosylated site and acrylic acid (AA) moiety for the apolipoprotein B of LDL. The adsorbent was synthesized by copolymerization of 4-vinyl phenyl boronic acid and AA. Five kinds of copolymers having different compositions were prepared and evaluated in terms of glc-LDL in vitro adsorption in human plasma. The adsorption behaviors were different depending on the polymer composition. The adsorbent having the AA composition from 50% to 90% showed very high selectivity for glc-LDL adsorption. The capability of selective adsorption was not impaired in human plasma. These results suggested that the adsorbent would be a promising material for glc-LDL apheresis.