Hence J.M. Verhagen

In Vivo Cell Seeding With Anti-CD34 Antibodies Successfully Accelerates Endothelialization but Stimulates Intimal Hyperplasia in Porcine Arteriovenous Expanded Polytetrafluoroethylene Grafts

Background—The patency of AV expanded polytetrafluoroethylene (ePTFE) grafts for hemodialysis is impaired by intimal hyperplasia (IH) at the venous outflow tract. The absence of a functional endothelial monolayer on the prosthetic grafts is an important stimulus for IH. In the present study, we evaluated the feasibility of capturing endothelial progenitor cells in vivo using anti-CD34 antibodies on ePTFE grafts to inhibit IH in porcine AV ePTFE grafts. Methods and Results—In 11 pigs, anti-CD34–coated ePTFE grafts were implanted between the carotid artery and internal jugular vein. Bare ePTFE grafts were implanted at the contralateral side. After 3 (n=2) or 28 (n=9) days, the pigs were terminated, and the AV grafts were excised for histological analysis and SEM. At 3 and 28 days after implantation, 95% and 85% of the coated graft surface was covered by endothelial cells. In contrast, no cell coverage was observed in the bare graft at 3 days, whereas at 28 days, bare grafts were partly covered with endothelial cells (32%; P=0.04). Twenty-eight days after implantation, IH at the venous anastomosis was strongly increased in anti-CD34–coated grafts (5.96±1.9 mm2) compared with bare grafts (1.70±0.4 mm2; P=0.03). This increase in IH coincided with enhanced cellular proliferation at the venous anastomosis. Conclusions—Autoseeding with anti-CD34 antibodies results in rapid endothelialization within 72 hours. Despite persistent endothelial graft coverage, IH at the outflow tract is increased profoundly at 4 weeks after implantation. Further modifications are required to stimulate the protective effects of trapped endothelial cells.

Rapid, arteriovenous graft failure due to intimal hyperplasia: a porcine, bilateral, carotid arteriovenous graft model.

BACKGROUNDnThe loss of patency constitutes the major complication of arteriovenous (AV) polytetrafluoroethylene hemodialysis grafts. In most cases, this graft failure is due to intimal hyperplasia at the venous outflow tract, including proliferation of vascular, smooth muscle cells and fibroblasts with deposition of extracellular matrix proteins. Thus far, procedures developed for improving patency have proven unsuccessful, which can be partly explained by the lack of relevant animal models. For this purpose, we developed a porcine model for AV graft failure that will allow the assessment of promising therapeutic strategies in the near future.nnnMATERIALS AND METHODSnIn 14 pigs, AV grafts were created bilaterally between the carotid artery and the jugular vein using expanded polytetrafluoroethylene. Two, 4 or 8 weeks after AV shunting, the grafts and adjacent vessels were excised and underwent histologic analysis.nnnRESULTSnFrom 2 weeks onwards, a thick neo-intima developed at the venous anastomosis, predominantly consisting of alpha-actin-positive vascular smooth muscle cells (VSMC). Intimal area increased over time, coinciding with a decreased graft flow. Grafts remained patent for at least 4 weeks. At 8 weeks, patency rates declined to less than 50% due to thrombus formation superimposed on progressive neo-intima formation.nnnCONCLUSIONSnImplantation of an AV graft between the carotid artery and jugular vein in pigs causes a rapid neo-intimal response, accompanied by a loss of patency of 50% at 8 weeks after surgery. This model offers a suitable tool to study local interventions aimed at the improvement of AV graft patency rates.

Toward endografting of the ascending aorta: Insight into dynamics using dynamic cine-CTA

PURPOSEnTo evaluate pulsatility and movement along the ascending thoracic aorta using dynamic electrocardiographically-gated 64-slice cine computed tomographic angiography (CTA).nnnMETHODSnDiameter and area change and center of mass (COM) movement of the ascending thoracic aorta was determined per cardiac cycle in 15 patients at surgically relevant anatomical levels: (A) 5 mm distal to the coronary arteries, (B) 5 mm proximal to the innominate artery, and (C) halfway up the ascending aorta. Additionally, COM movement was determined 1 cm (level P) and 2 cm (level Q) distal from the origins of the innominate, left carotid, and left subclavian arteries. Eight gated datasets covering the cardiac cycle were used to reconstruct images at each level perpendicular to the aortic lumen. The distance between important anatomical landmarks was determined.nnnRESULTSnAll levels showed significant cardiac cycle-induced diameter and area changes (p<0.001), with the largest pulsatility 5 mm distal to the coronary arteries. Mean maximum diameter changes were (A) 17.4%+/-4.8% (range 7.5%-27.5%), (B) 13.9%+/-3.5% (range 10.6%-25.0%), and (C) 12.9%+/-3.4% (8.3%-19.6%). Mean area changes were (A) 12.7%+/-5.5% (range 4.3%-21.8%), (B) 7.5%+/-2.0% (range 4.1%-11.0%), and (C) 5.6%+/-2.2% (range 1.9%-11.4%). Mean maximum COM movements were (A) 6.1+/-2.0 mm (range 2.7-9.0), (B) 2.3+/-1.1 mm (range 1.1-5.6), and (C) 3.6+/-1.5 mm (range 1.4-6.5). Mean COM movements of the innominate, left carotid, and left subclavian arteries, respectively, were (P) 1.9+/-0.7 mm (range 0.9-3.7), 2.4+/-0.6 mm (range 1.4-3.3), and 1.9+/-0.6 mm (range 0.8-2.8), and (Q) 1.8+/-0.7 mm (range 0.8-3.5), 1.8+/-0.6 mm (range 0.8-2.7), 1.9+/-0.6 mm (range 1.1-3.4).nnnCONCLUSIONnThe dynamics of the ascending thoracic aorta and the arch vessels are impressive, showing a wide range of 3-dimensional motions. Future ascending arch branched and fenestrated thoracic endograft designs must consider this active local environment, as it may have implications for durability, sealing, and ultimate clinical success.

Editor's Choice – Management of Descending Thoracic Aorta Diseases : Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS)

Editors Choice - Management of Descending Thoracic Aorta Diseases : Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS).

Use of dynamic computed tomography to evaluate pre- and postoperative aortic changes in AAA patients undergoing endovascular aneurysm repair

Purpose: To utilize dynamic computed tomographic angiography (CTA) on pre- and postoperative endovascular aneurysm repair (EVAR) patients to characterize cardiac-induced aortic motion within the aneurysm neck, an essential EVAR sealing zone. Methods: Electrocardiographically-gated CTA datasets were acquired utilizing a 64-slice Philips Brilliance CT scanner on 15 consecutive pre- and postoperative AAA patients. Axial pulsatility measurements were taken at 2 clinically relevant levels within the aneurysm neck: 2 cm above the highest renal artery and 1 cm below the lowest renal artery. Changes in aortic area and diameter were determined. Results: Significant aortic pulsatility exists within the aneurysm neck during the cardiac cycle. Preoperative aortic area increased significantly, with a maximum increase of up to 12.5%. The presence of an endograft did not affect aortic pulsatility (p = NS). Postoperative area also changed significantly during a heart cycle, with a maximum increase of up to 14.5%. Diameter measurements demonstrated an identical pattern, with significant pre- and postoperative intracardiac pulsatility within and above the aneurysm neck (p<0.05). An increase in maximum diameter change up to 15% was evident. Conclusion: Patients undergoing EVAR experience aortic diameter changes within and above the aneurysm neck. The presence of an endograft does not abrogate this response to intracardiac pressure changes. Static CT imaging may not adequately identify patients with large aortic pulsatility, potentially resulting in endograft undersizing, stent-graft migration, intermittent type I endoleaks, and poor patient outcomes. The current standard regime of 10% to 15% oversizing based on static CT may be inadequate for some patients.

Dynamic Aortic Changes in Patients with Thoracic Aortic Aneurysms Evaluated with Electrocardiography-Triggered Computed Tomographic Angiography before and after Thoracic Endovascular Aneurysm Repair: Preliminary Results

The purpose of this study was to utilize dynamic computed tomographic angiography (CTA) on pre- and postoperative thoracic endovascular aneurysm repair (TEVAR) patients to characterize cardiac pulsatility-induced aortic motion on essential TEVAR proximal sealing zones and to study the influence of endograft placement. Six pre- and six postoperative dynamic CTA studies were obtained in six patients with thoracic aortic aneurysms (TAAs) undergoing TEVAR. Data were acquired using a retrospective electrocardiography-triggered dynamic CTA scan, with eight reconstructed phases over the cardiac cycle. Scans were acquired during a single breath hold. Multiplanar reconstructions were made perpendicular to the aorta at five surgically relevant anatomical thoracic landmarks: 1 cm proximal to the innominate trunk, 1 cm proximal and 1 cm distal to the left subclavian artery, and 1 cm proximal and 3 cm distal to the proximal end of the stent. After segmentation of the aortic lumen in the images, diameter change and area change over the cardiac cycle were measured. Diameter change was measured through the center of mass of the aortic lumen, and the average change over 180 axis is presented. We found significant distention of the thoracic aortic arch and descending thoracic aorta during the cardiac cycle before and after TEVAR. Distention ranged 3-12% in diameter and 2-20% in area. This distention was preserved after TEVAR. Patients with TAA experience aortic diameter and area changes during the cardiac cycle. The magnitude, and hence the clinical importance, of this aortic distention varies among patients. After stent-graft placement, aortic distention throughout the cardiac cycle is preserved. This may have major implications for correct sizing of the endograft as well as for stent-graft design and durability as the forces on the stents may be much larger after implantation than initially anticipated by stent manufacturers.

In Vivo experiments with mesothelial cell seeded ePTFE vascular grafts

OBJECTIVESnTo investigate the influence of mesothelial cell (MC) seeding on patency and neointimal formation of small diameter ePTFE grafts in a canine model.nnnMATERIALS AND METHODSnMC were isolated from the omentum, cultured, seeded on fibronectin-coated ePTFE grafts (4 cm, 4 mm ID), and implanted in the carotid artery of five Beagle dogs. Each dog also received a non-seeded control graft. Patency was assessed by palpation immediately after implantation, and non-invasively by magnetic resonance angiography (MRA) after 1 week and just prior to sacrifice (4 weeks). Intimal thickness was quantified on histological sections by use of computer-aided morphometry.nnnRESULTSnAll grafts were patent after implantation. After 1 week, MRA showed the loss of lumen diameter in two seeded grafts. After 4 weeks, two seeded grafts were occluded, one seeded graft was severely stenosed, and all others were without angiographic lumen reduction. Histology and morphometry confirmed that two seeded grafts were occluded, and demonstrated that the other three seeded grafts showed significantly more intima formation (0.22-1.34 mm) than the control grafts (< 0.08 mm; p < 0.01).nnnCONCLUSIONSnThe MC seeding process decreases patency and increases neointimal formation of small diameter ePTFE grafts in dogs and does not seem to be useful for reduction of graft thrombogenicity.

Endovascular aneurysm repair alters renal artery movement: a preliminary evaluation using dynamic CTA.

Purpose: To observe the natural renal artery motion during cardiac cycles in patients with abdominal aortic aneurysm (AAA) and how the implantation of stent-grafts may distort this movement. Methods: Data on 29 renal arteries from 15 male patients (mean age 72.6 years, range 66–83) treated with Talent or Excluder stent-grafts were acquired using an electrocardiographically (ECG)-gated dynamic 64-slice CT scanner. ECG-triggered retrospective reconstructions were made at 8 equidistant time points over the R-R cardiac cycle. The gated datasets were reconstructed perpendicular to the center flow lumen of each renal artery at 1.2 and 2.4 cm from the renal ostium. Center of mass displacement was determined per cardiac cycle for pre- and post-EVAR renal arteries and compared. Results: Normal renal artery motion in AAA patients was impressive, with up to 3-mm movement both near and distant from the aorta (mean 2.0±0.6 mm, range 1.1–3.0). EVAR inhibited proximal renal motion, resulting in a 31% decrease in maximal movement (mean 1.4±0.7 mm, range 0.7–2.0; p≤0.05). Distal renal artery motion was unaffected by EVAR, with motion similar to the pre-EVAR state. Conclusion: ECG-gated dynamic CTA is feasible on a 64-slice scanner with a standard radiation dose and can detect potentially serious consequences of EVAR. EVAR alters renal artery motion by limiting proximal motion while leaving distal motion unaffected.

Thrombomodulin activity on mesothelial cells: perspectives for mesothelial cells as an alternative for endothelial cells for cell seeding on vascular grafts

Lining the luminal surface of prosthetic small diameter bypasses with endothelial cells (EC) will lower its thrombogenicity. Unfortunately, human EC are scarce. Mesothelial cells (MC) may be a valuable alternative for EC, since they are abundantly available and have antithrombotic and fibrinolytic properties. An important anticoagulant function of EC is due to thrombomodulin (TM) on the surface. The presence of TM on omentally derived human MC is not known but would increase the chance of successful use of MC for cell seeding procedures.

Long-term cardiac outcome in high-risk patients undergoing elective endovascular or open infrarenal abdominal aortic aneurysm repair.

OBJECTIVESnTo assess long-term outcome of patients at high cardiac risk undergoing endovascular or open AAA repair.nnnMETHODSnPatients undergoing open or endovascular infrarenal AAA repair with >or=3 cardiac risk factors and preoperative cardiac stress testing (DSE) at 2 university hospitals were studied. Main outcome was cardiac event free and overall survival. Multivariate Cox regression analysis was used to evaluate the influence of type of AAA repair on long-term outcome.nnnRESULTSnIn 124 patients (55 endovascular, 69 open) the number and type of cardiac risk factors, medication use and DSE results were similar in both groups. In multivariable analysis, adjusting for cardiac risk factors, stress test results, medication use, and propensity score endovascular repair was associated with improved cardiac event free survival (HR 0.54; 95% CI 0.30-0.98) but not with an overall survival benefit (HR 0.73; 95% CI 0.37-1.46). Importantly, statin therapy was associated with both improved overall survival (HR 0.42; 95% CI 0.21-0.83) and cardiac event free survival (HR 0.45; 95% CI 0.23-0.86).nnnCONCLUSIONSnThe perioperative cardiac benefit of endovascular AAA repair in high cardiac risk patients is sustained during long-term follow-up provided patients are on optimal medical therapy but it is not associated with improved overall long-term survival.