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.

Laparoscopic treatment of renal artery entrapment.

Renal artery entrapment by the diaphragmatic crus is a very infrequent cause of renovascular hypertension. We present the case of a young man who was assigned to our hospital with arterial hypertension and stenosis of the left renal artery. Extrinsic compression was diagnosed by duplex ultrasound and magnetic resonance angiography. We performed laparoscopic decompression using the transperitoneal retrorenal approach. Antihypertensive medication could be stopped thereafter and duplex ultrasound revealed a normal blood flow to the left renal artery. We therefore propose laparoscopic treatment of left renal artery entrapment as a minimally-invasive alternative to open surgery.

A biodegradable stent based on poly(L-lactide) and poly(4-hydroxybutyrate) for peripheral vascular application: preliminary experience in the pig.

PURPOSE: To assess the technical feasibility and biocompatibility of a novel stent based on poly(L-lactide) (PLLA) and poly(4-hydroxybutyrate) (P4HB) for peripheral vascular applications. METHODS: A polytetrafluoroethylene aortobi-iliac graft was implanted in 5 pigs through a midline abdominal incision. After transverse graft limb incision, 5 PLLA/P4HB stents and 5 metal stents (316L stainless steel) were randomly deployed at both iliac anastomotic sites with 6-mm balloon catheters. Angiography was performed to determine patency prior to sacrifice at 6 weeks. Stented segments were surgically explanted and processed for quantitative histomorphometry. Vascular injury and inflammation scores were assigned to the stented iliac segments. RESULTS: No animals were lost during follow-up. All PLLA/P4HB stents were deployed within 2 minutes by balloon inflation to 8 bars without rupture of the stent struts or anastomotic suture. All stents were patent on postprocedural angiography. Histological analysis showed no signs of excessive recoiling or collapse. PLLA/P4HB stents demonstrated decreased residual lumen area and increased neointimal area after 6 weeks (12.27+/-0.62 and 8.40+/-1.03 mm(2), respectively) compared to 316L stents (13.54+/-0.84 and 6.90+/-1.11 mm(2), respectively) as the result of differences in stent areas (PLLA/P4HB: 4.31+/-0.15 mm(2); 316L: 2.73+/-0.29 mm(2)). Vascular injury scores showed only mild vascular trauma for all stents (PLLA/P4HB: 0.41+/-0.59; 316L: 0.32+/-0.47). Inflammatory reaction was slightly higher around PLLA/P4HB stent struts (1.39+/-0.52) compared to 316L (1.09+/-0.50). CONCLUSION: Rapid balloon expansion of PLLA/P4HB stents is feasible without risk of strut rupture. PLLA/P4HB stents provide adequate mechanical stability after iliac anastomotic stenting in pigs. Smaller residual luminal areas in the PLLA/P4HB stents might have been caused by tissue ingrowth into the larger strut interspaces due to higher strut thickness (stent area) in this group. This limitation needs to be addressed in future work on the stent design.

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.

Rapid pacing for better placing: comparison of techniques for precise deployment of endografts in the thoracic aorta.

PURPOSE: To investigate the safety, efficacy, impact on positioning, and neurocognitive outcomes of 3 conceptually different methods of avoiding the "windsock" effect during thoracic stent-graft placement. METHODS: A retrospective review was conducted of 70 patients (48 men; mean age 63 years) who underwent elective or emergency stent-graft placement in the thoracic aorta for various pathologies. Twenty-seven patients (18 men; mean age 64+/-12 years) had stent-graft positioning during rapid right ventricular (RV) pacing at 180 to 200 beats per minute. Another 27 patients (18 men; mean age 62+/-12 years) had stent-graft placement under controlled hypotension (

Sirolimus-eluting biodegradable poly-L-lactide stent for peripheral vascular application: a preliminary study in porcine carotid arteries.

BACKGROUND: To assess technical feasibility and biocompatibility of a new Sirolimus (SIR)-eluting biodegradable poly-L-lactide (PLLA) stent for peripheral vascular application. MATERIAL AND METHODS: In 15 pigs, both common carotid arteries (CCA) were surgically exposed and clamped in the proximal segment. After transverse incision, 12 316L stents, 12 unloaded and 6 SIR-loaded PLLA stents mounted on 6.0 x 40-mm balloon catheters were randomly implanted into the CCA and inflated to 8 bar. Angiographic equipment was not available. Stented CCA were explanted after 1 week (6 pigs; 316L versus PLLA) and 6 weeks (9 pigs; 316L versus PLLA versus SIR-PLLA), and processed for quantitative histomorphometry and estimation of vascular inflammation and injury scores. RESULTS: No animals were lost during follow-up. All stents were patent on histological analysis without any signs of excessive recoiling or collapse. Unloaded PLLA stents showed decreased residual lumen area and increased neointimal area after 1 week (13.16 +/- 0.34, 1.94 +/- 0.26) and 6 weeks (11.57 +/- 0.30, 2.85 +/- 0.24) as compared with 316L stents (15.26 +/- 0.13, 1.27 +/- 0.41 and 13.99 +/- 0.51, 1.54 +/- 0.59). SIR-eluting stents demonstrated comparable neointimal area (1.75 +/- 0.38) and 50% lower intimal thickness as compared with 316L stents after 6 weeks, but a slightly decreased residual lumen (13.06 +/- 0.32) in the consequence of differences in strut thickness (PLLA, 270 microm; 316L, 155 microm). The vascular inflammation score against PLLA-stents could be reduced by Sirolimus. The vascular injury scores were low and similar in all groups. CONCLUSIONS: PLLA stents showed sufficient mechanical stability after porcine CCA stenting. By incorporation of Sirolimus, a significant reduction of the inflammatory and neointimal response to the PLLA stent was seen without systemic toxicity or thrombotic complications. These findings need to be assessed with longer follow-up to confirm maintenance of efficacy. The greater strut height of PLLA stents is a major limitation and requires modification.

Provisional extension to induce complete attachment after stent-graft placement in type B aortic dissection: the PETTICOAT concept.

PURPOSE: To report the use of a technique (PETTICOAT: provisional extension to induce complete attachment) to obliterate sustained abdominal false lumen flow and pressurization despite successful stent-graft sealing of the thoracic entry tear in patients with complicated type B aortic dissection. METHODS: Of 100 initial patients subjected to stent-graft repair for complex type B aortic dissection with thoracoabdominal extension, 12 patients (10 men; mean age 58.7 years, range 44-76) demonstrated distal true lumen collapse and a perfused abdominal false lumen despite successful sealing of the proximal tears. As an adjunctive or staged procedure, a scaffolding stent was placed for distal extension of the previously implanted stent-graft. In each case, a Sinus aortic stent, Fortress stent, or a Z-stent system was customized with maximum 2-mm oversizing versus the original stent-graft diameter. Magnetic resonance or computed tomographic angiography was performed at discharge, at 3 months, and then annually to determine false channel thrombosis, true and false lumen dimensions, and re-entry flow. RESULTS: Delivery was successful in all cases (100%). The compressed distal true lumen (mean 4+/-3 mm) was reconstructed to a mean width of 21+/-3 mm, and malperfusion was abolished without any obstruction of the abdominal side branches. At up to 1-year follow-up, there were no signs of expansion or distal progression of the scaffolded dissected aorta. All patients with complete thoracic thrombosis showed evidence of improved aortic remodeling; 1 patient with no false lumen thrombosis died at 11 months from thoracoabdominal aortic rupture. CONCLUSION: The PETTICOAT technique may offer a safe and promising adjunctive endovascular maneuver for patients with distal malapposition of the dissecting membrane and false lumen flow. The technique can both abolish distal true lumen collapse and enhance the remodeling process of the entire dissected aorta.

Iliac anastomotic stenting with a sirolimus-eluting biodegradable poly-L-lactide stent: a preliminary study after 6 weeks.

PURPOSE: To assess technical feasibility and biocompatibility of a new biodegradable sirolimus-eluting poly-L-lactide (PLLA) vascular anastomotic stent. METHODS: A polytetrafluoroethylene bifurcated graft was implanted in 9 pigs through a midline abdominal incision. After transverse graft limb incision, 6 unloaded PLLAs, 6 sirolimus-loaded PLLAs, and 6 unloaded stainless steel (316L) stents were randomly implanted at both iliac anastomotic sites. Stents were deployed with a 6-mm balloon under direct vision without the use of angiography. Prior to sacrifice after 6 weeks, contrast-enhanced computed tomography (CT) was performed to determine patency of the target vessels. Stented segments were surgically explanted and processed for histology to measure the mean luminal diameter and intimal thickness and to assign vascular injury and inflammation scores. RESULTS: No animals were lost during the study period. All stented graft limbs were patent on CT and histology. At the anastomotic sites and iliac arteries, the mean luminal diameter of SIR-PLLA stents (4.11+/-0.15 and 4.08+/-0.13 mm, respectively) were comparable to metal stents (4.23+/-0.35 and 4.21+/-0.26 mm, respectively), but significantly higher compared to unloaded PLLA stents [3.32+/-0.56 mm (p<0.001) and 3.29+/-0.39 mm (p=0.013), respectively]. At the iliac arteries, the mean intimal thickness was significantly lower with SIR-PLLA stents (0.09+/-0.02 mm) compared to unloaded PLLA stents (0.31+/-0.15 mm, p<0.001) and metal stents (0.19+/-0.04 mm, p=0.004). Vascular injury scores demonstrated only mild vascular trauma for all stents (SIR-PLLA: 0.42+/-0.63, PLLA: 0.51+/-0.62, metal: 0.50+/-0.62). Only mild inflammatory reaction was noted around SIR-PLLA stent struts (1.14+/-0.46), which was comparable to metal stents (1.27+/-0.45) but significantly lower than PLLA stents (1.79+/-0.56, p<0.001). CONCLUSION: SIR-PLLA stents showed comparable luminal diameter compared to metal stents, so incorporating sirolimus could reduce the inflammatory and neointimal response to PLLA stents. These findings need to be assessed with longer follow-up to confirm maintenance of efficacy.

Iliac anastomotic stenting with a biodegradable poly-L-lactide stent: a preliminary study after 1 and 6 weeks.

PURPOSE: To assess the technical feasibility, thrombogenicity, and biocompatibility of a new biodegradable poly-L-lactic acid (PLLA) anastomotic stent. METHODS: A polytetrafluoroethylene bifurcated graft was implanted in 17 pigs through a midline abdominal incision. After transverse graft incision, 17 316L stainless steel stents and 17 PLLA stents were randomly implanted at both iliac anastomotic sites and deployed with a 6-mm balloon under direct vision without angiography. Intended follow-up was 1 week in 6 pigs receiving oral acetylsalicylic acid (ASA) and in 7 pigs receiving ASA/clopidogrel; 4 pigs receiving ASA/clopidogrel were followed for 6 weeks. At the end of the study, the segments containing the stents were surgically explanted and processed for histology to measure the mean luminal diameter, intimal thickness, and the vascular injury and inflammation scores. RESULTS: Initial technical success of stent placement was achieved in all animals without rupture of the suture. Two pigs died (unrelated to the stent) at 3 days after operation (1 in groups A and B). At 1 week, all PLLA stents showed thrombotic occlusion with the use of ASA alone. In contrast, all PLLA stents remained patent with concurrent administration of ASA/clopidogrel. All metal stents were patent regardless of the antiplatelet regimen. The mean luminal diameter of patent PLLA stents (4.13+/-0.17 mm) was comparable to metal stents (4.27+/-0.35 mm, p=0.78) at 1 week, but significantly diminished at 6 weeks (3.21+/-0.44 versus 4.19+/-0.18 mm, p=0.005). Histological analysis showed no signs of excessive recoil. PLLA stents induced a higher inflammation score (1.79+/-0.56) and more intimal hyperplasia (0.34+/-0.11 mm) compared to metal stents [1.27+/-0.44 mm (p<0.001) and 0.18+/-0.04 mm (p=0.006), respectively] at 6 weeks. Vascular injury was comparable between PLLA and metal stents. CONCLUSION: Biodegradable PLLA stents showed higher thrombogenicity and reduced patency compared to metal stents during early follow-up. Although ASA and clopidogrel prevented thrombotic occlusion, the increased inflammatory response and neointima formation remain major concerns of PLLA stents. A solution to this problem might be the incorporation of anti-inflammatory drugs into the PLLA stent.

Axillary-axillary interarterial chest loop conduit as an alternative for chronic hemodialysis access.

OBJECTIVE: After exhaustion of all conventional arteriovenous (AV) access options, an alternative approach is an arterioarterial conduit. The purpose of this study was to examine the utility of an axillary-axillary (AA) interarterial (IA) access in this subset of patients. METHODS: A retrospective review was performed of all patients who underwent placement of an AA IA access. Patients were observed for functional aspects and complications. Outcomes were determined according to the Society for Vascular Surgery/American Association for Vascular Surgery standards for reports for dealing with AV accesses. RESULTS: Twenty patients (median age, 59 years; range, 41-82 years) underwent AA IA access placement under general anesthesia between May 2001 and December 2004. Exhausted upper extremity AV access options were found in 14 patients (70%), with central vein occlusion in 5 patients (25%), and 12 patients (60%) had ischemia from steal syndrome. High-output cardiac failure was present in one patient. Median follow-up was 7.4 months (range, 0.5-45.3 months). The 30-day perioperative mortality rate was 5%. There was one (5%) early access thrombosis that resulted in moderate ischemia. Late access thrombosis occurred in three patients (15%), and all cases were asymptomatic. Early postoperative bleeding necessitated surgical intervention in four patients (20%). Late graft infection (n = 1; 5%) occurred after repeated thrombectomy. The primary and secondary patency rate was 90% and 93%, respectively, at 6 months. CONCLUSIONS: This short-term initial study showed that the AA IA loop access could be implanted with acceptable perioperative morbidity and with an excellent secondary patency rate. Further follow-up is necessary to determine the long-term complication rate and to allow more reasonable comparison with other methods of access.