Objectives: To develop and test a new concept of the degradation kinetics of newly developed coronary stents consisting of magnesium alloys. Methods: Design of a coronary stent prototype consisting of the non-commercial magnesium based alloy AE21 (containing 2% aluminium and 1% rare earths) with an expected 50% loss of mass within six months. Eleven domestic pigs underwent coronary implantation of 20 stents (overstretch injury). Results: No stent caused major problems during implantation or showed signs of initial breakage in the histological evaluation. There were no thromboembolic events. Quantitative angiography at follow up showed a significant (p < 0.01) 40% loss of perfused lumen diameter between days 10 and 35, corresponding to neointima formation seen on histological analysis, and a 25% re-enlargement (p < 0.05) between days 35 and 56 caused by vascular remodelling (based on intravascular ultrasound) resulting from the loss of mechanical integrity of the stent. Inflammation (p < 0.001) and neointimal plaque area (p < 0.05) depended significantly on injury score. Planimetric degradation correlated with time (r = 0.67, p < 0.01). Conclusion: Vascular implants consisting of magnesium alloy degradable by biocorrosion seem to be a realistic alternative to permanent implants. P ermanent metallic implants are key treatment options in cardiovascular interventions. However, specific drawbacks limit their more widespread use. These limitations include thrombogenicity, permanent physical irritation, mismatches in mechanical behaviour between stented and non-stented vessel areas, long term endothelial dysfunction, inability to adapt to growth, non-permissive or disadvantageous characteristics for later surgical revascularisation, and chronic inflammatory local reactions. Degradable implants offer more physiological repair, reconstitution of local vascular compliance, and a temporary, limited, longitudinal, and radial straightening effect, including the possibility for growth. These implants are "fulfilling the mission and stepping away" 1 and may act as a new biomedical tool satisfying the requirements of compatibility and integration.2 However, most biodegradable synthetic polymer stents must have greater bulk to approximate the mechanical performance required in arteries. Many also induce exaggerated acute and chronic inflammatory responses during degradation. 3To address this issue, we developed and tested a new concept of degradation after endovascular implantation of tailored magnesium alloys. We anticipated a more useful combination of mechanical stability over a limited time and complete degradation of the implants. METHODS AlloysMagnesium alloys containing small amounts of aluminium, manganese, zinc, lithium, and rare earth elements were preselected for their mechanical aspects and tested in vitro for degradation kinetics (synthetic seawater, Ringer lactate, and porcine and human serum; calculated stent half lives for different magnesium alloys were between minutes and about half a year) and the potential in...

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Magnesium alloy stents are safe and are associated with less neointima formation; however, reduced neointima did not result in larger lumen.

After 3 months, the primary clinical patency and limb salvage rates suggest a potentially promising performance of these AMS devices in the treatment of below-knee lesions in CLI patients.

Elective coronary stenting was effective in the treatment of restenosis after balloon angioplasty. Stenting resulted in a lower rate of recurrent stenosis despite a higher incidence of subacute thrombosis.

Several reports have established the concept of nitric oxide synthase (NOS) gene transfer for inhibiting smooth muscle cell (SMC) proliferation after vascular injury. To minimize potential risks associated with viral gene transfer, we developed a liposome-based gene transfer approach employing inducible NOS (iNOS) overexpression for inhibition of stent-induced neointimal lesion formation. Therapeutic lipoplexes were transferred to femoral or coronary arteries of Goettingen minipigs, using the Infiltrator local drug delivery device. Efficiency of local iNOS lipoplex transfer was analyzed by iNOS-specific immunohistochemistry. NO-mediated inhibition of stent-induced neointimal lesion formation was analyzed by intravascular ultrasound (IVUS) and computerized morphometry. Gene transfer efficiency increased dose dependently to a maximum of 44.3 +/- 4.2% iNOS-positive vessel area (dose, 2 microg of iNOS lipoplex). Proliferating cell nuclear antigen (PCNA) expression of medial SMCs (immunohistochemistry) was inhibited significantly by transfer of 2 microg of iNOS lipoplexes (111 +/- 27 cells [iNOS] versus 481 +/- 67 cells [control; PCNA-positive medial cells]). IVUS analysis demonstrated that local transfer of iNOS lipoplexes resulted in a significant reduction of femoral in-stent plaque area (control, 40.85 +/- 6.37 mm(2); iNOS, 24.69 +/- 1.8 mm(2); p = 0.03). Coronary in-stent lesion formation was reduced by about 45% as determined by histologic morphometry (control, 4.0 +/- 0.29; iNOS, 2.2 +/- 0.30; p < 0.01). In conclusion, this study demonstrates that local intramural delivery of iNOS lipoplexes can exert therapeutic effects in inhibiting stent-induced neointimal lesion formation. Together with the nonviral character of this gene therapy approach, these findings may have important impact on the transition of NOS-based gene therapy to clinical practice.

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Progression of CAV is a complex process, modified by changes in the vascular geometry. Especially within the 1st year after HTX, luminal loss is influenced not only by an increase in plaque area but by a decrease in total vessel volume as well.