Vascular Response Toward an Absorbable Sirolimus-eluting Polymeric Scaffold for Vascular Application in a Model of Normal Porcine Carotid Arteries.

BACKGROUND: Fully absorbable polymeric scaffolds, as a potential alternative to permanent metallic stents, are entering the clinical field. The aim of this study is to assess the in vivo biocompatibility of a novel Sirolimus-eluting (SIR) absorbable scaffold based on poly(L-lactide) (PLLA) and poly(4-hydroxybutyrate) (P4HB) for interventional application. METHODS: Absorbable PLLA/P4HB scaffolds either loaded with SIR coating or unloaded scaffolds were implanted interventionally into common carotid arteries of 14 female. Bare metal stents (BMS) served as control. Peroral dual anti-platelet therapy was administered throughout the study. Stented common carotid arteries segments were explanted after 4 weeks, and assessed histomorphometrically. RESULTS: The absorbable scaffolds showed a decreased residual lumen area and higher stenosis after 4 weeks (PLLA/P4HB: 6.56 ± 0.41 mm² and 37.56 ± 4.67%; SIR-PLLA/P4HB: 6.90 ± 0.58 mm² and 35.60 ± 3.15%) as compared to BMS (15.29 ± 1.86 mm² and 7.65 ± 2.27%). Incorporation of SIR reduced the significantly higher inflammation of unloaded scaffolds however not to a level compared to bare metal stent (PLLA/P4HB: 1.20 ± 0.19; SIR-PLLA/P4HB: 0.96 ± 0.24; BMS: 0.54 ± 0.12). In contrast, the BMS showed a slightly elevated vascular injury score (0.74 ± 0.15), as compared to the PLLA/P4HB (0.54 ± 0.20) and the SIR-PLLA/P4HB (0.48 ± 0.15) groups. CONCLUSION: In this preclinical model, the new absorbable polymeric (SIR-) scaffolds showed similar technical feasability and safety for vascular application as the permanent metal stents. The higher inflammatory propensity of the polymeric scaffolds was slightly reduced by SIR-coating. A smaller strut thickness of the polymeric scaffolds might have been a positive effect on tissue ingrowth between the struts and needs to be addressed in future work on the stent design.

Can Recognition of Spinal Ischemia Be Improved? Application of Motor-Evoked Potentials, Serum Markers, and Breath Gas Analysis in an Acutely Instrumented Pig Model.

BACKGROUND: Paraplegia due to spinal cord ischemia (SCI) is a serious complication after repair of thoracoabdominal aortic aneurysms. For prevention and early treatment of spinal ischemia, intraoperative monitoring of spinal cord integrity is essential. This study was intended to improve recognition of SCI through a combination of transcranial motor-evoked potentials (tc-MEPs), serum markers, and innovative breath analysis. METHODS: In 9 female German Landrace pigs, tc-MEPs were captured, markers of neuronal damage were determined in blood, and volatile organic compounds (VOCs) were analyzed in exhaled air. After thoraco-phrenico-laparotomy, SCI was initiated through sequential clamping (n = 4) or permanently ligating (n = 5) SAs of the abdominal and thoracic aorta in caudocranial orientation until a drop in the tc-MEPs to at least 25% of the baseline was recorded. VOCs in breath were determined by means of solid-phase microextraction coupled with gas chromatography-mass spectrometry. After waking up, clinical and neurological status was evaluated (Tarlov score). Spinal cord histology was obtained in postmortem. RESULTS: Permanent vessel ligature induced a worse neurological outcome and a higher number of necrotic motor neurons compared to clamping. Changes of serum markers remained unspecific. After laparotomy, exhaled acetone and isopropanol showed highest concentrations, and pentane and hexane increased during ischemia-reperfusion injury. CONCLUSIONS: To mimic spinal ischemia occurring in humans during aortic aneurysm repair, animal models have to be meticulously evaluated concerning vascular anatomy and function. Volatiles from breath indicated metabolic stress during surgery and oxidative damage through ischemia reperfusion. Breath VOCs may provide complimentary information to conventional monitoring methods.

Development of a sirolimus-eluting poly (L-lactide)/poly(4-hydroxybutyrate) absorbable stent for peripheral vascular intervention.

Fully absorbable drug-eluting stent platforms are currently entering the clinical arena for the interventional treatment of coronary artery disease. This new technology also holds potential for application in peripheral vascular settings. Our study reports on the development of a sirolimus- (SIR) eluting absorbable polymer stent made from a blend of poly(l-lactide) and poly(4-hydroxybutyrate) (PLLA/P4HB) for peripheral vascular intervention. Stent prototypes were laser-cut from PLLA/P4HB tubes (I.D.=2.2 mm, t=250 µm), spray-coated with different PLLA/P4HB/SIR solutions, and bench-tested to determine expansion properties, fatigue, trackability and in vitro drug release kinetics. The stent prototypes were expanded with a 5.0 × 20 mm balloon catheter, and exhibited a recoil of 3.6% upon balloon deflation. Stent collapse pressure of 0.4 bar (300 mm Hg) was measured under external pressure load. Sustained scaffolding properties were observed in vitro over 14 weeks of radial fatigue loading (50 ± 25 mm Hg at 1.2 Hz). Trackability was demonstrated in bench tests with an 8 French contralateral introducer sheath. SIR release kinetics were adjusted over a broad range by varying the PLLA/P4HB ratio of the coating matrix. The newly developed absorbable SIR-eluting PLLA/P4HB stent successfully fulfilled the requirements for peripheral vascular intervention under in vitro conditions.

Hybrid aortic arch repair for complicated type B aortic dissection.

OBJECTIVE: This study analyzed the outcome of a combined endovascular and debranching procedure for hybrid aortic arch repair (HAR) in patients with complicated type B aortic dissection. METHODS: Between February 2006 and August 2012, HAR was performed in 75 consecutive patients, with retrospective analysis of a subgroup of 45 patients who underwent HAR with complicated acute (n = 10), subacute (n = 7), or chronic (n = 28) type B dissection as the underlying disease. Descriptive statistics were computed for continuous and categoric variables. The interval to death or last follow-up was estimated using the Kaplan-Meier method. RESULTS: The patients were a mean age of 59.9 ± 10.7 years (median, 59.2; range, 35-78 years). Complete supra-aortic debranching was performed in six (13%) in zone 0 (procedure time, 200 minutes; range, 185-365 minutes) and partial debranching in 39 (87%), comprising 16 (36%) in zone 1 (procedure time, 120 minutes; range, 75-250 minutes) and 23 (51%) in zone 2 (procedure time, 91 minutes; range, 70-210 minutes). Technical success was achieved in 86.7% (39 of 45). Thirty-day mortality was 4.4% (two of 45), with an in-hospital mortality of 11.1% (five of 45) as a result of three additional deaths after days 33, 35, and 111. Comparing HAR for type B dissection after complete debranching in six and partial debranching in 39, the overall in-hospital mortality was 67% (four of six) and 2.6% (one of 39), respectively. After a median follow-up of 20.8 months (range, 0.3-70 months), the overall mortality was 13.3% (six of 45), with Kaplan-Meier survival estimate of 85% at 1 year. Stroke rate was 8.8% (four of 45). Paraplegia developed in one patient (2.2%), with complete recovery after spinal drainage. Cardiac complications occurred in three patients (6.7%), pulmonary complications in 10 (22.2%), and renal insufficiency requiring dialysis developed in five (11%). Retrograde dissection occurred in one patient (2.2%) 14 days after complete debranching and zone 0 thoracic endovascular aortic repair, with fatal outcome. No bypass dysfunction was seen during follow-up. The overall early and late endoleak rates were 27% (12 of 44) and 43% (13 of 30), respectively. Eight patients (18%) required reintervention, with freedom of reintervention in 91% at 1 year and 81% at 2 years. CONCLUSIONS: HAR in zone 1 and 2 appears a viable alternative to conventional aortic arch surgery in patients with complicated type B dissection. Stroke and endoleaks remain complications that need to be addressed. Treatment of type B aortic dissection with complete supra-aortic debranching and thoracic endovascular aortic repair in zone 0, however, is associated with high mortality, which might be reduced by improved technology using branched stent grafts.

Enhanced visualization of biodegradable polymeric vascular scaffolds by incorporation of gold, silver and magnetite nanoparticles.

Due to improved tissue regeneration and the enabling of post-operative minimally invasive interventions in the same vessel segment, biodegradable polymeric scaffolds represent a competitive approach to permanent metallic stents in vascular applications. Despite these advantages some challenges, such as the improvement of the scaffold mechanics and enhancement of scaffold visibility during the implantation procedure, are persisting. Therefore, the scope of our studies was to investigate the potential of gold, silver and magnetite nanoparticles incorporated in a polymeric blend of poly(L-lactide)/poly(4-hydroxybutyrate) for image enhancement in X-ray, magnetic resonance or near-infrared imaging. Their impact on mechanical properties of such modified scaffold materials was also evaluated.

A biodegradable slotted tube stent based on poly(L-lactide) and poly(4-hydroxybutyrate) for rapid balloon-expansion.

Safe vascular stent application requires rapid expansion of the stent to minimize the risk of procedural ischemia. While high expansion speeds can be achieved with metallic stents, they are not necessarily feasible with biodegradable polymeric stents due to the viscoelastic material behavior. This study reports on a novel biodegradable polymer blend material based on poly(L-lactide) (PLLA) and poly(4-hydroxybutyrate) (P4HB), and describes the mechanical properties and in vitro degradation behavior of a balloon-expandable slotted tube stent concept. The stent prototypes with nominal dimensions of 6.0 x 25 mm were manufactured by laser machining of solution cast PLLA/P4HB tubes (I.D. = 2.8 mm, d = 300 microm). The stents were expanded within 1 min by balloon inflation to 8 bar, after 5 min preconditioning in 37 degrees C water. Recoil and collapse pressure were 4.2% and 1.1 bar, respectively. During in vitro degradation collapse pressure initially increased to a maximum at 4 w and then decreased thereafter. After 48 w, molecular weight was decreased by 82%. In summary, the PLLA/P4HB slotted tube stents allowed for rapid balloon-expansion and exhibited adequate mechanical scaffolding properties suitable for a broad range of vascular and non-vascular applications.