Vascular endothelial growth factor enhances atherosclerotic plaque progression.

Vascular endothelial growth factor (VEGF) can promote angiogenesis but may also exert certain effects to alter the rate of atherosclerotic plaque development. To evaluate this potential impact on plaque progression, we treated cholesterol-fed mice doubly deficient in apolipoprotein E/apolipoprotein B100 with low doses of VEGF (2 microg/kg) or albumin. VEGF significantly increased macrophage levels in bone marrow and peripheral blood and increased plaque area 5-, 14- and 4-fold compared with controls at weeks 1, 2 and 3, respectively. Plaque macrophage and endothelial cell content also increased disproportionately over controls. In order to confirm that the VEGF-mediated plaque progression was not species-specific, the experiment was repeated in cholesterol-fed rabbits at the three-week timepoint, which showed comparable increases in plaque progression.

In situ revascularization with rifampicin-soaked silver polyester graft for aortic infection: Results of a retrospective monocentric series of 18 cases.

OBJECTIVE: To evaluate the short and long-term results of in situ prosthetic graft treatment using rifampicin-soaked silver polyester graft in patients with aortic infection. MATERIAL AND METHOD: All the patients surgically managed in our center for an aortic infection were retrospectively analyzed. The primary endpoint was the intra-hospital mortality, secondary outcomes were limb salvage, persistent or recurrent infection, prosthetic graft patency, and long-term survival. RESULTS: From January 2004 to December 2015, 18 consecutive patients (12 men and 6 women) were operated on for aortic infection. Six mycotic aneurysms and 12 prosthetic infections, including 8 para-entero-prosthetic fistulas, were treated. In 5 cases, surgery was performed in emergency. During the early postoperative period, we performed one major amputation and two aortic infections were persistent. Intra-hospital mortality was 27.7%. The median follow-up among the 13 surviving patients was 26 months. During follow-up, none of the 13 patients presented reinfection or bypass thrombosis. CONCLUSION: This series shows that in situ revascularization with rifampicin-soaked silver polyester graft for aortic infection have results in agreement with the literature in terms of intra-hospital mortality with a low reinfection rate.

Incidence and determinants of spinal cord ischaemia in stent-graft repair of the thoracic aorta.

OBJECTIVES: Endovascular repair of descending thoracic aortic lesions is associated with a substantial risk of perioperative spinal cord ischaemia (SCI) which may lead to permanent paraplegia. We performed a retrospective analysis of our experience in the endovascular treatment of descending thoracic aortic lesions to define the incidence of SCI and to identify factors that contributed to its development. METHODS: 67 consecutive patients underwent stent graft repair for descending thoracic aortic lesions including degenerative aneurysm (n=19), type B dissection (acute n=2, chronic n=15), traumatic rupture (acute n=14, chronic n=4), penetrating aortic ulcer (n=5), anastomotic false aneurysm (n=4), mycotic aneurysm (n=3) and embolic aortic lesion (n=1) between June 2000 and June 2005. All procedures were performed with the patient under general anaesthesia and strict blood pressure monitoring. No patient had intra-operative monitoring of spinal evoked potential or cerebrospinal fluid (CSF) drainage to prevent SCI. Neurological evaluation was realized after recovery from general anaesthesia. Fifteen factors, including nature of aortic disease, length of aortic coverage, number of stent-grafts, coverage of the distal third of the thoracic aorta and subclavian artery coverage, were investigated as possible predictors of postoperative SCI. RESULTS: Five patients (7.5%) had postoperative neurological deficits (immediate n=2, delayed n=3) referable to SCI. Univariate analysis showed that length of aortic coverage (p<0.001) and number of stent-grafts deployed (p=0.02) were significant predictors of SCI. Multivariate logistic regression analysis showed that length of aortic coverage was the only independent significant predictor of SCI. ROC curve analysis revealed 205mm of aortic length coverage as the threshold for increased risk of postoperative SCI (p=0.001), with specificity and sensitivity of 95.2 and 80% respectively. CONCLUSION: In our study, length of aortic coverage is the only independent predictive factor of SCI after endovascular treatment with 205mm as a threshold for increased risk. Hence, methods to prevent SCI, especially those aimed at restoration of an adequate spinal cord perfusion pressure, should be offered to patients requiring extensive coverage of the descending thoracic aorta.

High-efficiency endovascular gene delivery via therapeutic ultrasound.

OBJECTIVES: We studied enhancement of local gene delivery to the arterial wall by using an endovascular catheter ultrasound (US). BACKGROUND: Ultrasound exposure is standard for enhancement of in vitro gene delivery. We postulate that in vivo endovascular applications can be safely developed. METHODS: We used a rabbit model of arterial mechanical overdilation injury. After arterial overdilation, US catheters were introduced in bilateral rabbit femoral arteries and perfused with plasmidor adenovirus-expressing blue fluorescent protein (BFP) or phosphate buffered saline. One side received endovascular US (2 MHz, 50 W/cm2, 16 min), and the contralateral artery did not. RESULTS: Relative to controls, US exposure enhanced BFP expression measured via fluorescence 12-fold for plasmid (1,502.1+/-927.3 vs. 18,053.9+/-11,612 microm2, p < 0.05) and 19-fold for adenovirus (877.1+/-577.7 vs. 17,213.15+/-3,892 microm2, p < 0.05) while increasing cell death for the adenovirus group only (26+/-5.78% vs. 13+/-2.55%, p < 0.012). CONCLUSIONS: Endovascular US enhanced vascular gene delivery and increased the efficiency of nonviral platforms to levels previously attained only by adenoviral strategies.

[Stent-graft treatment of a ruptured aortic graft: a case report]. / Traitement endovasculaire d'une rupture de pontage aortique.

The authors report the clinical and imaging features of a patient with rupture of an aortoiliac graft successfully treated by endovascular approach. The endovascular treatment is easy to perform and effective. The main pitfall of this technique is the limited availability of stent-grafts.

[Endovascular treatment of isthmic aortic rupture: use of second generation stent grafts]. / Traitement endovasculaire des ruptures isthmiques de l'aorte chez le polytraumatisé: utilisation de stents de deuxième génération.

OBJECTIVE: Prospective analysis of endovascular management of traumatic isthmic rupture with second generation stent grafts. STUDY DESIGN: Prospective analysis and follow-up. PATIENTS: Ten consecutive multiple injured patients presenting an acute isthmic traumatic rupture who underwent an endovascular repair with second generation stent grafts. METHODS AND RESULTS: The aortic injury was diagnosed by spiral computed tomography scan. The appropriate time to repair was decided according to multidisciplinary decision after analysis of associated injuries status and mediastinal lesions evolution. Endovascular repair was successfully completed in all patients under general anaesthesia without requirement of haemodynamic manipulations. Despite a prolonged length of stay related to associated injuries, all patients were discharged from hospital without migration of devices or complication related to the endovascular procedure. After a 20 months follow-up (range 6 - 38 months), all patients were alive with a satisfactory CT scan analysis. CONCLUSION: The immediate availability of the second generation of stents-grafts allowed the endovascular treatment of isthmic rupture without haemodynamic manipulations or massive heparinization. The analysis of this selected series reinforces the interest of this non-invasive technique for anaesthetists especially in polytraumatized patients.

Development of a platform to evaluate and limit in-stent restenosis.

The objective of this work was to develop a platform to evaluate and deliver putative therapeutic agents for in-stent restenosis. Arterial stenting is applied in more than 60% of balloon angioplasties for treating cardiovascular disease. However, stented arteries encounter accelerated rates of restenosis. No prior platform has allowed evaluation or local management of in-stent restenosis without perturbing the very system being examined. A stainless steel, balloon-expandable stent was modified to serve as an ablumenal drug delivery platform. Several combinations of bioerodible polymer microspheres and gels were evaluated for channel retention under in vitro flow and in vivo conditions. A stent-anchored hybrid system prevented material embolization under all conditions. Unlike prior platforms, these stents do not alter local inflammation or in-stent plaque formation relative to conventional Palmaz-Schatz stents after in vivo deployment. The system also proved sensitive enough to detect plaque reduction with an antirestenotic agent. We conclude that a platform to evaluate and deliver therapeutic agents for in-stent restenosis has been achieved.

Intravenous leiomyomatosis with caval involvement: report of a case with radical resection and venous replacement.

Intravenous leiomyomatosis is a rare, histologically benign neoplasm that may be malignant in its specific tendency to intravascular extension. A case of intravenous leiomyomatosis with extension into the entire inferior vena cava in a 41-year-old woman is described. The patient was diagnosed with syncope 3 years after hysterectomy and was treated with a 1-stage procedure including venous replacement.

Perivascular release of insulin-like growth factor-1 limits neointima formation in the balloon-injured artery by redirecting smooth muscle cell migration.

PURPOSE: Insulin-like growth factor-1 (IGF-1) is a potent chemoattractant to vascular smooth muscle cells (SMCs). The authors hypothesize that perivascular release of IGF-1 in vivo can direct migration of SMCs away from the lumen and reduce neointima formation in a rabbit model of arterial balloon injury. MATERIALS AND METHODS: Balloon angioplasty of the common femoral arteries was performed in adult male New Zealand White rabbits (n = 8 per treatment group) and controlled release microspheres delivering either IGF-1 or blank control treatment were implanted perivascularly at the angioplasty site prior to surgical closure. At 7 days, five arteries per group were harvested and cross-sections were subjected to anti-PCNA (proliferating cell nuclear antigen) immunostaining to determine the number and distribution of proliferating SMCs. At 28 days, the remaining three arteries per group were harvested and sections were evaluated for intima-to-media (I/M) ratios by means of VVG-Masson staining. One-way analysis of variance with Fisher protected least significant difference post hoc testing was used to determine statistical significance at P < .05. RESULTS: At 7 days, PCNA(+) medial SMCs assumed a significantly more peripheral (ie, further from lumen) distribution in the vessel wall with use of perivascular IGF-1 than with use of blank treatment (P < .05). Overall SMC proliferation was not significantly different, thus the change in distribution was likely due to directionally altered SMC migration. At 28 days, perivascular IGF-1 significantly decreased I/M ratios by 44% relative to control treatment (P < .05). CONCLUSIONS: Perivascular release of IGF-1 can directionally guide SMC migration away from the lumen and reduce neointima in the balloon-injured artery. This novel strategy might have implications in the development of antirestenosis therapies.

Local delivery of NO-donor molsidomine post-PTA improves haemodynamics, wall mechanics and histomorphometry in atherosclerotic porcine SFA.

OBJECTIVES: we investigated the therapeutic effect of angioplasty with local drug delivery (LDD) of the wall-accumulating NO-donor molsidomine (M) in the superficial femoral arteries (SFA) of atherosclerotic swine. MATERIALS AND METHODS: atherosclerotic Pietrin swines (n=14) underwent PTA-LDD-M (4 mg/2 ml) vs contralateral PTA-LDD-Placebo in the SFA using a channelled balloon angioplasty catheter. Invasive and colour Doppler energy (CDE) assessments of haemodynamics and wall mechanics were performed at 24 h (n=4) and 5 months (n=10). Immuno-histolabelling of cell proliferation and histomorphometry were serially performed in perfusion fixed SFA samples. RESULTS: at 24 h, PCNA-positive nuclei revealed 33+/-14 and 12+/-3 proliferating cells/mm2 at placebo and molsidomine PTA-LDD sites, respectively (p<0.001). At 5 months, PTA-LDD-M vessels, compared with PTA-LDD-P, had increased compliance (66+/-9 vs 11+/-4 ml/mmHg) and lowered impedance (0.11+/-0.05 vs 0.45+/-0.14 mmHg/ml x min(-1)) (p<0.05). CDE revealed low, middle and high velocity peaks at 7.5, 20 and 35, and 8, 15 and 22 cm x s(-1) in systolic and diastolic flows, respectively; and PTA-LDD-M prevented emergence of restenosis-associated increases in low blood velocities (p<0.01). PTA-LDD-M inhibited restenotic intimal thickening and medial thinning which decreased mean lumenal diameter in placebo-treated (2.6+/-0.3) as compared to molsidomine-treated (3.4+/-0.3 mm) vessels (p<0.05). CONCLUSIONS: in the atherosclerotic porcine SFA model, PTA-LDD with molsidomine consistently improved haemodynamic wall mechanics, lowered cell proliferation and prevented late lumen loss observed with PTA-LDD with placebo.

Compliance matching stent placement in the carotid artery of the swine promotes optimal blood flow and attenuates restenosis.

OBJECTIVES: We assessed the value of a gradient-compliant stent in an animal model. METHODS: Bilateral carotid arteries were stented with nitinol stents having variable-oversizing, variable-stiffness, and with (CMS, 10 animals) and without (SMART, four animals) compliance-matching endings. Angiography, hemodynamic, scanning-electron-microscopic and histological analyses were performed at 3-month. The protocol was completed in 14 among 19 swines. RESULTS: Transient (1-month) exaggerated recoil, attributable to stress-induced phasic inhibition of vasorelaxation, developed at CMS endings. At mid-term, all stents were endothelialized; CMS-stents, but not SMART-stents, were incorporated into walls (one-strut-thickness). Restenosis developed outside SMART-stents (cell migration+wall-compensatory enlargement) whereas CMS-stents elicited no or focalized cell-accumulations at endings that bulged vascular walls radially outward. SMART-stents were blood-flow neutral, whereas CMS-stents favored (higher-stiffness, higher-oversizing) or opposed (lower-stiffness, less-oversizing) carotid blood flow. CONCLUSIONS: Direct carotid stenting with stents having compliance-matched endings and specific requirements of stiffness and oversizing can optimize blood flow to the brain and restrict local restenosis.

Therapeutic elastase inhibition by alpha-1-antitrypsin gene transfer limits neointima formation in normal rabbits.

PURPOSE: Alpha-1-antitrypsin (AAT) is the major circulating elastase inhibitor. Deficiency of elastase inhibition leads to emphysema and vascular abnormalities including accelerated neointima. Because recent evidence suggests that tissue AAT levels determine inhibitory function, the authors hypothesize that local tissue-based expression of AAT limits elastase activity sufficiently to guide arterial response to injury. MATERIALS AND METHODS: Rabbit common femoral arteries were injured by mechanical overdilation and treated with buffer, viral control, or an adenovirus expressing AAT (Ad/AAT). After 3 and 28 days, intima-to-media (I/M) ratios were evaluated. Additionally, early changes in elastase inhibition potential (3 d), extracellular elastin and collagen content (3 d), and local macrophage and neutrophil infiltration (7 d) were determined. RESULTS: Ad/AAT significantly decreased neointima formation after mechanical dilation injury after 28 days: buffer controls exhibited mean I/M ratios of 0.76 +/- 0.06, whereas viral controls reached 0.77 +/- 0.09; in contrast, Ad/AAT reduced I/M ratios to 0.44 +/- 0.06. Both early elastin and collagen content were preserved in the Ad/AAT group relative to controls. The Ad/AAT group also reversed the local inflammation that characterized viral controls. CONCLUSIONS: This strategy demonstrates that local increases in elastase inhibition potential promote a neointima-resistant small-caliber artery, which may offer new promise in management of patients undergoing angioplasty.