The performance of heparin modified poly(ε-caprolactone) small diameter tissue engineering vascular graft in canine-A long-term pilot experiment in vivo.

Long-term in vivo observation in large animal model is critical for evaluating the potential of small diameter tissue engineering vascular graft (SDTEVG) in clinical application, but is rarely reported. In this study, a SDTEVG is fabricated by the electrospinning of poly(ε-caprolactone) and subsequent heparin modification. SDTEVG is implanted into canine's abdominal aorta for 511 days in order to investigate its clinical feasibility. An active and robust remodeling process was characterized by a confluent endothelium, macrophage infiltrate, extracellular matrix deposition and remodeling on the explanted graft. The immunohistochemical and immunofluorescence analysis further exhibit the regeneration of endothelium and smooth muscle layer on tunica intima and tunica media, respectively. Thus, long-term follow-up reveals viable neovessel formation beyond graft degradation. Furthermore, the von Kossa staining exhibits no occurrence of calcification. However, although no TEVG failure or rupture happens during the follow-up, the aneurysm is found by both Doppler ultrasonic and gross observation. Consequently, as-prepared TEVG shows promising potential in vascular tissue engineering if it can be appropriately strengthened to prevent the occurrence of aneurysm.

Short and Mid Term Outcomes of Cryopreserved Abdominal Aortic Allografts Used as a Substitute for Infected Prosthetic Grafts in 200 Patients.

OBJECTIVE: To investigate the use of cryopreserved arterial allografts (CAA) as a substitute for infected infrarenal aortic prostheses, and its outcomes. METHODS: A single centre retrospective study of consecutive patients receiving an abdominal aortic CAA after removal of an infected graft was conducted between January 1997 and December 2013. The primary outcome was the rate of allograft related revision surgery. Secondary outcomes were the 30 day mortality rate, survival, primary patency, limb salvage, and infection recurrence. Allograft ruptures secondary to infection and risk factors for allograft failure were also investigated. RESULTS: Two hundred patients (mean age 64.2 ± 9.4 years) were included. In 56 (28%) cases, infection was related to an enteric fistula. The mean follow up duration was 4.1 years. The 30 day mortality rate was 11%. Early revision surgery was needed in 59 patients (29.5%). Among them, 15 (7.5%) were allograft related and led to the death of three patients (1.5%), corresponding to a 7.5% 30 day allograft related revision surgery rate. During the first six months, 17 (8.5%) patients experienced 21 events with complete or partial rupture (pseudo-aneurysm) of the allograft responsible for five (2.5%) deaths, corresponding to a re-infection rate of 8.5%. The multivariable analysis showed that diabetes and pseudo-aneurysm of the native aorta on presentation were predictive factors for short term allograft rupture. After six months, 25 (12.5%) patients experienced long term allograft complications (rupture, n = 2, 1%; pseudo-aneurysm, n = 6, 3%; aneurysm, n = 2, 1%; thrombosis, n = 11, 5.5%; stenosis, n = 4, 2%;) requiring revision surgery resulting in one death. The five year rates of survival, allograft related revision surgery, limb salvage, primary patency, and infection recurrence were 56%, 30%, 89%, 80%, and 12%, respectively. CONCLUSION: CAAs provide acceptable results to treat aortic graft infection with few early graft related fatal complications. Long term allograft related complications are quite common but are associated with low mortality and amputation rates.

Sleeve Technique is Superior to End-to-End Anastomosis and Cuff Technology in Mouse Model of Graft Vascular Disease.

BACKGROUND: Graft vascular disease (GVD) is the main reason of late transplanted organ failure, which limits the long-term survival of patients. Murine aortic transplant is widely used in the field to understand the mechanisms leading to GVD. Currently, 3 major techniques, end-to-end anastomosis, sleeve suture and cuff technology, have been used to study the mechanism of GVD. However, which method is more suitable in mouse model of GVD? Herein, we compared these 3 surgical techniques in a mouse allograft arteriosclerosis model to determine the technique with the most appreciable outcomes. METHODS: Male C57Bl/6 (H-2b) and BALB/c (H-2d) mice were used for aorta transplantation with these 3 techniques. These 3 techniques were compared with regard to donor artery acquisition time, artery anastomosis time, overall surgical time, the amount of bleeding of each technique and the success rate of surgery. Hematoxylin and eosin (H&E) and Masson staining were used to examine the pathological changes of grafted vessels. The protein expression of phospho-NF-κb P65 and PCNA were determined to validate laminar flow and proliferative capacity of neointima obtained from different surgical and control groups. RESULTS: Sleeve suture had a shorter vascular anastomosis time and total operation time than end-to-end anastomosis and cuff technique. Sleeve suture and cuff technique had significantly fewer amount of bleeding from the site of vascular anastomosis than end-to-end anastomosis. Moreover, sleeve suture had the highest success rate among these 3 techniques. There was no difference in the degree of graft stenosis and collagen deposition between these 3 techniques. In addition, there was no significant difference in the expression of phospho-NF-κb P65and PCNA between the experimental group. CONCLUSIONS: Sleeve suture is superior to end-to-end anastomosis and cuff technique with regard to vascular grafting in the murine model.

Overlapping and distinct biological effects of IL-6 classic and trans-signaling in vascular endothelial cells.

IL-6 affects tissue protective/reparative and inflammatory properties of vascular endothelial cells (ECs). This cytokine can signal to cells through classic and trans-signaling mechanisms, which are differentiated based on the expression of IL-6 receptor (IL-6R) on the surface of target cells. The biological effects of these IL-6-signaling mechanisms are distinct and have implications for vascular pathologies. We have directly compared IL-6 classic and trans-signaling in ECs. Human ECs expressed IL-6R in culture and in situ in coronary arteries from heart transplants. Stimulation of human ECs with IL-6, to model classic signaling, triggered the activation of phosphatidylinositol 3-kinase (PI3K)-Akt and ERK1/2 signaling pathways, whereas stimulation with IL-6 + sIL-6R, to model trans-signaling, triggered activation of STAT3, PI3K-Akt, and ERK1/2 pathways. IL-6 classic signaling reduced persistent injury of ECs in an allograft model of vascular rejection and inhibited cell death induced by growth factor withdrawal. When inflammatory effects were examined, IL-6 classic signaling did not induce ICAM or CCL2 expression but was sufficient to induce secretion of CXCL8 and support transmigration of neutrophil-like cells. IL-6 trans-signaling induced all inflammatory effects studied. Our findings show that IL-6 classic and trans-signaling have overlapping but distinct properties in controlling EC survival and inflammatory activation. This has implications for understanding the effects of IL-6 receptor-blocking therapies as well as for vascular responses in inflammatory and immune conditions.

Transplantation of a single kidney from pediatric donors less than 10 kg to children with poor access to transplantation: a two-year outcome analysis.

BACKGROUND: Access to kidney transplantation by uremic children is very limited due to the lack of donors in many countries. We sought to explore small pediatric kidney donors as a strategy to provide transplant opportunities for uremic children. METHODS: A total of 56 cases of single pediatric kidney transplantation and 26 cases of en bloc kidney transplantation from pediatric donors with body weight (BW) less than 10 kg were performed in two transplant centers in China and the transplant outcomes were retrospectively analyzed. RESULTS: The 1-year and 2-year death-censored graft survival in the en bloc kidney transplantation (KTx) group was inferior to that in the single KTx group. Subgroup analysis of the single KTx group found that the 1-year and 2-year death-censored graft survival in the group where the donor BW was between 5 and 10 kg was 97.7 and 90.0%, respectively. However, graft survival was significantly decreased when donor BW was ≤5 kg (p < 0.01), mainly because of the higher rate of thrombosis (p = 0.035). In the single KTx group, the graft length was increased from 6.7 cm at day 7 to 10.5 cm at 36 months posttransplant. The estimated glomerular filtration rate increased up to 24 months posttransplant. Delayed graft function and urethral complications were more common in the group with BW was ≤5 kg. CONCLUSIONS: Our study suggests that single kidney transplantation from donors weighing over 5 kg to pediatric recipients is a feasible option for children with poor access to transplantation.

Editor's Choice - Sex Related Differences in Peri-operative Mortality after Elective Repair of an Asymptomatic Abdominal Aortic Aneurysm in the Netherlands: a Retrospective Analysis of 2013 to 2018.

OBJECTIVE: The aim was to compare peri-operative (30 day and/or in hospital) mortality between women and men in the Netherlands after elective repair of an asymptomatic abdominal aortic aneurysm (AAA). METHODS: This was a retrospective study using data from the Dutch Surgical Aneurysm Audit (DSAA), a mandatory nationwide registry of patients undergoing AAA repair in the Netherlands. Patients who underwent elective open surgical (OSR) or endovascular aneurysm repair (EVAR) of an asymptomatic abdominal aortic aneurysm (AAA) between 2013 and 2018 were included. Absolute risk differences (ARDs) with 95% confidence intervals (CIs) in peri-operative mortality between women and men were estimated. Logistic regression analyses were performed to estimate adjusted odds ratios (ORs) for mortality. Confounders included pre-operative cardiac and pulmonary comorbidity, serum haemoglobin, serum creatinine, type of AAA repair, and AAA diameter. RESULTS: Some 1662 women and 9637 men were included, of whom 507 (30.5%) women and 2056 (21.3%) men underwent OSR (p < .001). Crude peri-operative mortality was 3.01% in women and 1.60% in men (ARD = 1.41%, 95% CI 0.64-2.37). This significant difference was also observed for OSR (ARD = 2.63%, 95% CI 0.43-5.36), but not for EVAR (ARD = 0.36%, 95% CI -0.16 to 1.17). Female sex remained associated with peri-operative mortality after adjusting for confounders (OR = 1.79, 95% CI 1.20-2.65, p = .004), which was similarly observed for OSR (OR = 1.85, 95% CI 1.16-2.94, p = .01), but not for EVAR (OR = 1.46, 95% CI 0.72-2.95, p = .29). CONCLUSIONS: Peri-operative mortality after elective repair of an asymptomatic AAA in the Netherlands is higher in women than in men. This disparity might be explained by the higher peri-operative mortality in women undergoing OSR, because no such difference was found in patients undergoing EVAR. Yet, it is likely that there are unaccounted factors at play since female sex remained significantly associated with mortality after adjusting for type of repair.

Hybrid electrospun rapamycin-loaded small-diameter decellularized vascular grafts effectively inhibit intimal hyperplasia.

For the surgical treatment of coronary artery disease, renal artery stenosis and other peripheral vascular diseases, there is significant demand for small diameter (inner diameter <6 mm) vascular grafts. However, autologous grafts are not always available when the substitute vascular grafts are severely diseased. In our previous work, hybrid small-diameter vascular grafts were successfully fabricated by combining electrospun polycaprolactone (PCL) and decellularized rat aorta (DRA). However, histological assessments of these grafts revealed the development of intimal hyperplasia, indicating potential negative impacts on the long-term patency of these grafts. To address this challenge, PCL nanofibers blended with rapamycin (RM) were electrospun outside the decellularized vascular graft to fabricate a RM-loaded hybrid tissue-engineered vascular graft (RM-HTEV), endowing the graft with a drug delivery function to prevent intimal hyperplasia. RM-HTEV possessed superior mechanical properties compared to DRA and exhibited a sustained drug release profile. To evaluate the applicability of RM-HTEV in vivo, abdominal aorta transplantation was performed on rats. Doppler sonography showed that the grafts were functional for up to 8 weeks in vivo. Moreover, histological analysis of explanted grafts 12 weeks postimplantation demonstrated that RM-HTEV significantly decreased neo-intimal hyperplasia compared with HTEV, without impairing reendothelialization and M2 macrophage polarization. Overall, RM-HTEV represents a promising strategy for developing small-diameter vascular grafts with great clinical translational potential. STATEMENT OF SIGNIFICANCE: In this study, a new type of rapamycin-loaded hybrid tissue-engineered vascular graft (RM-HTEV) was fabricated using electrospinning technology. The unique hybrid bi-layer structure endowed the RM-HTEV with multi-functionality: the exterior rapamycin-loaded electrospun PCL nanofibrous layer enhanced the mechanical properties of the graft and possessed drug releasing property; the interior decellularized aorta layer with porous structure could facilitate cell proliferation and migration. In in vivo implantation experiment, RM-HTEV exhibited satisfying long-term patency rate and significantly inhibited intimal hyperplasia without impairing re-endothelialization and M2 macrophage polarization. This strategy is expected to be a promising strategy for developing bioactive small-diameter vascular grafts with great clinical translational potential.

Regulation of the inflammatory response by vascular grafts modified with Aspirin-Triggered Resolvin D1 promotes blood vessel regeneration.

The unabated inflammatory response is often the cause for inhibited vascular regeneration of transplanted small-diameter vascular grafts (diameter <6 mm) in vascular replacement therapies. We proposed that stimulating inflammatory resolution could be an effective approach for treatment of chronic vascular graft inflammation after transplantation. Aspirin-Triggered Resolvin D1 (AT-RvD1) plays critical roles in driving cellular processes toward the resolution of inflammation and suppressing downstream inflammatory signaling pathways. With the aim to facilitate vascular regeneration, we developed a polycaprolactone (PCL) vascular graft loaded with AT-RvD1. The results showed that AT-RvD1 promoted macrophage polarization into M2 macrophages in vitro. Macrophages pretreated with AT-RvD1 conditioned medium promoted endothelial cell tube formation. Furthermore, in vivo implantation was performed by replacing rat abdominal aorta. We observed fast endothelialization and enhanced smooth muscle regeneration in rats that received the AT-RvD1-containing graft implants. The presence of AT-RvD1 induced infiltration of a large number of M2 macrophages and integrin α4-positive (CD49d+) neutrophils into the graft wall after implantation. Vascular graft RNA-Seq analysis revealed that AT-RvD1 inhibited leukocyte and neutrophil migration and activation. Results also indicated that macrophage polarization to the M2 phenotype was promoted on day 7 post-implantation. These results demonstrated the ability of locally delivered AT-RvD1 to increase pro-regenerative immune subpopulations and promote vascular tissue regeneration. STATEMENT OF SIGNIFICANCE: Chronic inflammation is a key deciding factor in the failure of vascular regeneration of transplanted small-diameter vascular grafts (diameter <6 mm). Aspirin-triggered Resolvin D1 (AT-RvD1) is a critical driving force in cellular resolution inflammation and suppresses inflammatory signaling. Herein, we developed an electrospun polycaprolactone (PCL) vascular graft loaded with AT-RvD1. In vivo implantation was performed by replacing rat abdominal aorta and AT-RvD1-loaded grafts showed rapid endothelialization, enhanced capillary formation, and excellent smooth muscle regeneration by regulating inflammatory reaction and promoting its rapid resolution. Thus, our study provided new perspectives for long-term vascular graft survival and integration with the host tissue. We believe that AT-RvD1 can be widely applied in tissue engineering owing to its anti-inflammatory and therapeutic effects.

Accelerated endothelialization and suppressed thrombus formation of acellular vascular grafts by modifying with neointima-inducing peptide: A time-dependent analysis of graft patency in rat-abdominal transplantation model.

Acellular blood vessels have clinical potential as tissue-engineered vascular grafts. However, neointima is hard to form on their luminal surface. We recently reported the integrin α4ß1 ligand peptide (Arg-Glu-Asp-Val) conjugated with a repetitive Pro-Hyp-Gly sequence as luminal surface modifier. By using this peptide, excellent patency of tissue-engineered small-caliber long-bypass grafts in minipig transplantation model was achieved. Here, the time-dependent change of the graft patency is investigated by using rat abdominal transplantation model. In vitro test showed that 86% of the endothelial cells were adhered to the peptide-modified graft surface, while cells were scarcely adhered on the unmodified and random peptide-modified surfaces. After transplantation in the abdominal aorta, the patency of unmodified and random peptide-modified grafts gradually decreased during two to three weeks and reached 20-40% in four weeks. In contrast, 80% of the modified grafts were patent without any thrombus formation at four weeks. These results suggest that the luminal surface modifier was bound to acellular surface through (Pro-Hyp-Gly)7 sequence and improved the in vivo graft patency by endothelialization and thrombus formation suppression.

Editor's Choice - Cryopreserved Allografts for Arterial Reconstruction after Aorto-Iliac Infection: A Systematic Review and Meta-Analysis.

OBJECTIVE: Native and aortic graft infections are rare, but they represent one of the most life threatening complications of vascular surgery. Several materials and surgical approaches have been developed so far. Among them, cryopreserved allografts have been proposed as a treatment option. A systematic review and meta-analysis was conducted to investigate the role of cryopreserved allografts for arterial reconstruction after aorto-iliac infection. METHODS: The current meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Patient baseline characteristics were investigated, along with 30 outcomes after use of cryopreserved arterial allografts for reconstruction after aorto-iliac infection. Pooled proportions with 95% CIs of outcome rates were calculated. RESULTS: A total of 31 studies, including 1,377 patients, finally participated in the meta-analysis. Among the early outcomes, 30 day mortality was 14.91% (95% CI 11.78-18.31). Peri-anastomotic rupture/allograft disruption rate was 5.90% (95% CI 2.77-9.88), while pooled aneurysmal degeneration/allograft dilatation was 4.99% (95% CI 1.60-9.68). A pooled rate of 3.11% (95% CI 1.60-4.98) was estimated for pseudoaneurysm formation after the use of cryopreserved arterial allografts, while the allograft thrombotic/stenotic complication rate and peri-anastomotic infection were 12.19% (95% CI 7.90-17.15) and 3.32% (95% CI 1.90-5.03), respectively. Mortality during follow up was 19.24% (95% CI 11.97-27.58), while allograft related mortality during follow up was 3.58% (95% CI 1.56-6.15). A pooled allograft related re-operation rate was estimated at 24.87% (95% CI 17.89-32.51). CONCLUSIONS: The use of cryopreserved allograft seems to be a safe and durable option with acceptable outcomes for treatment of aorto-iliac infection.

Mfn2 inhibits chronic rejection of the rat abdominal aorta by regulating TGF-ß1 levels.

OBJECTIVES: The various forms of chronic rejection share a common histological appearance termed allograft arteriosclerosis. In the early stages thereof, apoptosis of vascular smooth muscle cells (VSMC) is obviously reduced, associated with vascular intimal thickening. High-level expression of the HSG/Mfn2 gene promotes apoptosis of rat VSMC. However, the role and mechanism of Mfn2 in inhibition of chronic allograft rejection have not been described. METHODS: In the present study, we transfected transplanted abdominal aortas of donor Lewis rats with an Mfn2-encoding or control lentivirus. And then We transplanted the donor aortas to the corresponding aortal positions in recipient rats. Transplanted aortas were collected on days 30, 60, and 90 and Masson stained to measure intimal thicknesses. Immunohistochemistry would be used to confirm TGF-ß1, Mfn2 and TGF-ß-R2 expression in different groups. RESULTS: Our results confirm that high-level expression of Mfn2 lowers the expression of TGF-ß1, reduces the intimal thickness of transplanted rat abdominal aorta, and retards the process of chronic rejection. CONCLUSION: Mfn2 influences TGF-ß/smad pathway and may function as potential chronic rejection inhibitor.

Effect of surgically guided axonal regrowth into a 3-way-conduit (isogeneic trifurcated aorta) on functional recovery after facial-nerve reconstruction: Experimental study in rats.

BACKGROUND: The "post-paralytic syndrome" after facial nerve reconstruction has been attributed to (i) malfunctioning axonal guidance at the fascicular (branches) level, (ii) collateral branching of the transected axons at the lesion site, and (iii) intensive intramuscular terminal sprouting of regenerating axons which causes poly-innervation of the neuromuscular junctions (NMJ). OBJECTIVE: The first two reasons were approached by an innovative technique which should provide the re-growing axons optimal conditions to elongate and selectively re-innervate their original muscle groups. METHODS: The transected facial nerve trunk was inserted into a 3-way-conduit (from isogeneic rat abdominal aorta) which should "guide" the re-growing facial axons to the three main branches of the facial nerve (zygomatic, buccal and marginal mandibular). The effect of this method was tested also on hypoglossal axons after hypoglossal-facial anastomosis (HFA). Coaptational (classic) FFA (facial-facial anastomosis) and HFA served as controls. RESULTS: When compared to their coaptation (classic) alternatives, both types of 3-way-conduit operations (FFA and HFA) promoted a trend for reduction in the collateral axonal branching (the proportion of double- or triple-labelled perikarya after retrograde tracing was slightly reduced). In contrast, poly-innervation of NMJ in the levator labii superioris muscle was increased and vibrissal (whisking) function was worsened. CONCLUSIONS: The use of 3-way-conduit provides no advantages to classic coaptation. Should the latter be impossible (too large interstump defects requiring too long interpositional nerve grafts), this type of reconstruction may be applied. (230 words).

Lanthanum carbonate, a phosphate binder, inhibits calcification of implanted aortic allografts in a rat model.

OBJECTIVES: Calcification is one of the major postoperative problems after aortic allograft implantation. We hypothesized that phosphate binders, lanthanum carbonate and calcium carbonate inhibit calcification of implanted aortic allografts and verified this hypothesis using a rat model. METHODS: Aortas were harvested from 4-week-old Brown Norway rats and implanted into the subdermal space of 4-week-old Lewis rats. Twenty-seven recipient Lewis rats were divided into Group N, Group L, and Group C (9 rats per group), which were fed a normal diet, a normal diet containing 3% lanthanum carbonate, and a normal diet containing 3% calcium carbonate, respectively. Implanted aortic allografts were explanted 2 weeks later. Calcification of aortic allografts was evaluated using von Kossa staining and calcium content assay. Calcification score was defined in von Kossa staining as 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Serum calcium and phosphorus levels at euthanasia were measured. RESULTS: Calcification scores were 2.6, 1.2, and 0.8, and calcium content was 48.9, 15.8, and 8.9 mg/dry·g, in Groups N, L, and C, respectively. Calcification was significantly reduced in Groups L and C. Serum calcium level was 11.5, 12.2, and 13.5 mg/dl, and serum phosphorus level was 15.4, 12.5, and 11.7 mg/dl, in Groups N, L, and C, respectively. Serum calcium level in Group C was significantly higher than in the other two groups. CONCLUSIONS: Lanthanum carbonate and calcium carbonate significantly reduced calcification of implanted aortic allografts in young rats. Although calcium carbonate induced hypercalcemia, lanthanum carbonate has significant potential to inhibit calcification of implanted aortic allografts.

[Mycotic aorta aneurysm treated with an autologous venous graft].

Systemic side effects, including sepsis, due to bacille Calmette-Guérin treatment for carcinoma in situ in the bladder, are observed in 15% of the patients. In rare cases, patients have developed systemic infections and mycotic aneurysms. In this case report, a 72-year-old man developed a mycotic aortic aneurysm, and the appropriate tuberculostatic drugs had no effect on his systemic infection. He was successfully treated surgically, replacing the affected aortic segment with an autologous venous graft, resulting in complete remission. A follow-up PET-CT three months later showed no sign of ongoing aortic infection.

Investigation of the expressions of MMPs and TIMPs between isogeneic and allogeneic rat aortic transplantation.

The present study investigated the effects of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in transplantation-associated arteriosclerosis by observing their expression in transplanted aortas in rats. Allogenic and isogenic abdominal aortic transplantations were performed and grafts were removed from the recipients at the designated time points (day 7, 14, 28 and 56 post transplantation). Hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and western blot analysis were used to evaluate the grafts. Significant proliferation of the intima was observed in the allogenic transplantation groups (P<0.05). The expressions of MMPs and TIMPs in the allografts were significantly increased compared with the isografts, and the suppression of MMP2 in allografts reduced injury after transplantation. The present study concluded that the imbalance of MMPs and TIMPs led to the disturbance of synthesis and the degradation of the extracellular matrix and it may represent a key cause of chronic rejection.

Feasibility Study of a Novel Thoraco-abdominal Aortic Hybrid Device (SPIDER-graft) in a Translational Pig Model.

BACKGROUND: The hybrid SPIDER-graft consists of a proximal descending aortic stent graft and a conventional six branched Dacron graft for open abdominal aortic repair. Technical feasibility with regard to avoiding thoracotomy and extracorporeal circulation (ECC) during thoraco-abdominal aortic hybrid repair and peri-procedural safety of this novel device are unknown. MATERIAL AND METHODS: This was a feasibility and safety study in domestic pigs (75-85 kg). The abdominal aorta including iliac bifurcation, left renal artery, and visceral arteries were exposed via retroperitoneal access. The right iliac branch was first temporarily anastomosed end to side to the distal aorta via partial clamping. During inflow reduction and infra-coeliac cross-clamping, the coeliac trunk (CT) was divided and the proximal stent graft portion of the SPIDER-graft was deployed into the descending aorta via the CT ostium. Retrograde visceral and antegrade aorto-iliac blood flow was maintained via the iliac side branch. The visceral, renal, and iliac arteries were sequentially anastomosed, finally replacing the first iliac end to side anastomosis. Technical success, blood flow, periods of ischaemia, and peri-procedural complications were evaluated after intra-operative completion angiography and post-operative computed tomography angiography. RESULTS: Six animals underwent successful thoracic stent graft deployment and distal open reconstruction without peri-operative death. The median thoracic graft implantation time was 4.5 min, and the median ischaemia times before reperfusion were 10 min for the CT, 8 min for the superior mesenteric artery, 13 min for the right renal artery, and 22 min for the left renal artery. Angiography demonstrated appropriate graft implantation and blood flow measurements confirmed sufficient blood flow through all side branches. CONCLUSION: In this translational pig model, thoraco-abdominal hybrid repair using the novel SPIDER-graft was successful in avoiding thoracotomy and ECC. Technical feasibility and safety appear promising, but need to be reassessed in humans.

The Safety of Device Registries for Endovascular Abdominal Aortic Aneurysm Repair: Systematic Review and Meta-regression.

OBJECTIVES: New and re-designed stent grafts for endovascular aortic aneurysm repair (EVAR) are released regularly. Manufacturers use data from registries to assess stent graft performance, but little is known about the ability of such registries to detect rates of clinically relevant complications. The aim of this paper was to perform a systematic review and meta-analysis to determine pooled failure rates for EVAR stent grafts, to define an acceptable non-inferiority limit for these devices, and then to calculate the number of patients needed for a new device to achieve non-inferiority against published devices. DATA SOURCES AND REVIEW METHODS: MEDLINE and EMBASE were searched for studies reporting outcomes of specific EVAR grafts being used for intact infrarenal abdominal aortic aneurysms, from inception to November 2016. Meta-regression was performed to pool data and calculate the patient numbers needed to detect non-inferiority of a future graft performance. An expert consensus was performed to define adequate standards for device safety. RESULTS: One hundred and forty-seven moderate quality papers involving 27,058 patients were included. Multiple outcomes were pooled. Of these, the estimated rate (±standard error) of overall endoleak (excluding Type II) at 2 years was 5.7 ± 0.6%. The pooled re-intervention rate was 11.1 ± 0.7% at 2 years. There were differences in pooled endoleak rates between different stent graft types. Expert consensus defined non-inferiority as better performance than the worst performing 25% of stent grafts. The most popular outcome in the expert consensus was cumulative endoleak rate (excluding Type II). The number of patients who would need to be enrolled in a registry to demonstrate non-inferiority at this level was 525. Only two of 147 included studies achieved this. The second most popular choice in the expert consensus was re-intervention rate; 492 patients are required to demonstrate this. CONCLUSIONS: Five hundred and twenty-five patients need to be entered into a registry to demonstrate non-inferiority to previous stent grafts. Almost all previous publications have captured lower patient numbers. With performance varying between devices, and new devices being introduced regularly, there is an urgent need to capture higher quality long-term data on EVAR stent grafts.

Using the Sleeve Technique in a Mouse Model of Aortic Transplantation - An Instructional Video.

Orthotopic aortic transplantation using the sleeve technique reduces injury to the aorta with failure rate of only 10-20%. The time to anastomose the aorta in mice using the sleeve method was short and easy averaging 20 min, permitting studies of iso/allo grafts. The following article describes the aortic transplantation procedure used in our laboratory. The mice were anesthetized with a mixture of 1.5% volume isoflurane and 100% oxygen through a face mask. At this point, the segment of the aorta between the renal arteries and its bifurcation was separated from the vena cava, freely prepared and clampedat the proximal and distal segments with a single silk suture. Prior to the removal of the aorta, a saline solution containing heparin was injected into the inferior vena cava. Then the aorta was cut between the clamps and a saline heparin solution was used to flush the lumen. The sleeve technique with monofilament sutures was used in order to transplant the abdominal aorta in the orthotopic position.

In vitro and in vivo evaluation of a small-caliber coaxial electrospun vascular graft loaded with heparin and VEGF.

INTRODUCTION: To date, clinically available expanded polytetrafluoro-ethylene (ePTFE) vascular grafts are suboptimal for reconstructing small caliber (D < 6 mm) arteries, owing to thrombosis in early and restenosis in late stage. Our aim in this preliminary study was to fabricate a nano-fibrous vascular graft which was biofunctionalized with VEGF165 and heparin. The short term performance was evaluated both in vitro and in vivo. METHOD: Four-mm caliber grafts were prepared by the coaxial-elctrospun technique, which consisted of poly(l-lactide-co-caprolactone) [P(LLA-CL)] collagen and elastin. Heparin and endothelial cell growth factor-165 (VEGF165) were encapsulated in the core of the fibrous. Controlled release of the heparin and VEGF165 were evaluated for 28 days. Endothelial cells were cultured on the electrospun grafts or ePTFE grafts as controls. The cellular adhesion, proliferation and morphology were examined. Electrospun or ePTFE grafts were randomly implanted into a rabbit infrarenal aortic replacement model (n = 30) for 28 days without any antiplatelet therapy. At the termination, all grafts were examined by Doppler ultrasound and then evaluated with histology and scanning electron microscopy. RESULTS: The cumulative release amount of heparin (6.93 ± 1.03 mg) and VEGF165 (22.17 ± 5.56 µg) during 28 days were measured. Endothelial cells cultured on electrospun grafts showed significantly higher attachment efficiency and proliferation compared to the ePTFE ones (P < 0.001). At 2 h more ECs had attached to the P(LLA-CL)/Collagen/Elatin grafts (83.26 ± 8.02%) compared to P(LLA-CL) (67.07 ± 4.16%) and ePTFE (46.87 ± 8.85%). ECs proliferated faster on VEGF loaded grafts (O.D = 2.9 ± 1.2, n = 12) compared to ePTFE (O.D = 1.7 ± 1.0, n = 12). The patency was significantly higher in electrospun grafts (86.6%) than ePTFE grafts (40.0%) (P = 0.021). Correspondingly, the microscope images of electrospun implants showed little thrombus when compared with the ePTFE implants. CONCLUSION: Biofunctionalized electrospun graft showed surgical properties, hemocompatibility and higher short-term patency compared with the ePTFE grafts. Despite good early performances, profound study should be designed for long-term evaluation.