Exclusion of lumbar arteries by aortic endovascular grafts: can angiography demonstrate sealing characteristics?

BACKGROUND: This study evaluates sealing characteristics of two designs of endovascular grafts by angiographic demonstration of exclusion of porcine lumbar arteries. METHODS: 6 endovascular grafts (3 self-expandable with integrated polyurethane wall versus 3 nitinol structures covered with polyester fabric) were implanted in 6 porcine aortae. Perfusion of lumbar arteries was assessed by angiography after implantation and by angiography and dissection at graft explantation after 4 +/- 2 months. Tissue healing was evaluated by light and scanning electron microscopy. RESULTS: Immediate exclusion of the lumbar arteries was achieved in 14/31 vessels (12 by polyurethane grafts and 2 by polyester grafts, p < 0.001). Follow-up angiography and dissection at explantation revealed perfusion of 30/31 lumbar arteries with a collateral network in most cases. Another reason for reperfusion of initially excluded branches was distention of the polyurethane grafts with resulting shortening allowing reperfusion of 8 of the 31 originally covered branches. Histological examination revealed a complete neointimal lining and a tight contact between endovascular grafts and aorta. CONCLUSIONS: The immediate angiographic demonstration of exclusion of lumbar arteries predicts sealing characteristics of endovascular grafts. Later angiographic reappearance is due to development of a collateral network and possible shortening of self-expandable devices.

Stent-assisted coiling of bifurcation aneurysms may improve endovascular treatment: a critical evaluation in an experimental model.

BACKGROUND AND PURPOSE: Endovascular treatment of wide-neck bifurcation aneurysms often results in incomplete occlusion or aneurysm recurrence. The goals of this study were to compare results of coil embolization with or without the assistance of self-expandable stents and to examine how stents may influence neointima formation. MATERIALS AND METHODS: Wide-neck bifurcation aneurysms were constructed in 24 animals and, after 4-6 weeks, were randomly allocated to 1 of 5 groups: 1) coil embolization using the assistance of 1 braided stent (n = 5); 2) coil embolization using the assistance of 2 braided stents in a Y configuration (n = 5); 3) coil embolization without stent assistance (n = 6); 4) Y-stenting alone (n = 4); and 5) untreated controls (n = 4). Angiographic results were compared at baseline and at 12 weeks, by using an ordinal scale. Neointima formation at the neck at 12 weeks was compared among groups by using a semiquantitative grading scale. Bench studies were performed to assess stent porosities. RESULTS: Initial angiographic results were improved with single stent-assisted coiling compared with simple coiling (P = .013). Angiographic results at 12 weeks were improved with any stent assistance (P = .014). Neointimal closure of the aneurysm neck was similar with or without stent assistance (P = .908), with neointima covering coil loops but rarely stent struts. Y-stent placement alone had no therapeutic effect. Bench studies showed that porosities can be decreased with stent compaction, but a relatively stable porous transition zone was a limiting factor. CONCLUSIONS: Stent-assisted coiling may improve results of embolization by allowing more complete initial coiling, but these high-porosity stents did not provide a scaffold for more complete neointimal closure of aneurysms.

The use of the vac in complex wounds - does it work and how?

Background: Complex wounds pose a major challenge in reconstructive and trauma surgery. Several approaches to increase the healing process have been proposed in the last decades. In this study we study the mechanism of action of the Vacuum Assisted Closure device in diabetic wounds. Methods: Full-thickness wounds were excised in diabetic mice and treated with the VAC device or its isolated components: an occlusive dressing (OD) alone, subathmospheric pressure at 125 mm Hg (Suction), and a polyurethane foam without (Foam) and with (Foamc) downward compression of approximately 125 mm Hg. The last goups were treated with either the complete VAC device (VAC) or with a silicne interface that alows fluid removel (Mepithel-VAC). The effects of the treatment modes on the wound surface were quantified by a two-dimensional immunohistochemical staging system based on vasculature, as defined by blood vessel density (CD31) and cell proliferation (defined by ki67 positivity), 7 days post wounding. Finite element modelling was used to predict wound surface deformation under dressing modes and cross sections of in situ fixed tissues were used to measure actual microstrain. Results: The foam-wound interface of the Vacuum Assisted Closure device causes significant wound stains (60%) causing a deformation of the single cell level leading to a profound upregulation of cell proliferation (4-fold) and angiogenisis (2.2-fold) compared to OD treated wounds. Polyurethane foam exposure itself causes a frather unspecific angiogenic response (Foamc, 2 - fold, Foam, 2.2 - fold) without changes of the cell proliferation rate of the wound bed. Suction alone without a specific interface does not have an effect on meassured parameters, showing similar results to untreated wounds. A perforated silicone interface caused a significant lower microdeforamtion of the wound bed correlating to changes of the wound tissues. Conclusion: The Vacuum Assisted Closure device induce significanttissue growth in diabetic wounds. The wound foam interface under suction causes profound macrodeformation that stimulates tissue growth by angiogenesis and cell proliferation. It needs to be taken in consideration that in the clinical setting different wound types may profit from different elements of this suction device.

FOXC2 and NFATc1 control formation and maturation of collecting lymphatic vessels

The mechanisms of blood vessel maturation into distinct parts of the blood vasculature such as arteries, veins, and capillaries have been the subject of intense investigation over recent years. In contrast, our knowledge of lymphatic vessel maturation is still fragmentary. In this study, we provide a molecular and morphological characterization of the major steps in the maturation of the primary lymphatic capillary plexus into collecting lymphatic vessels during development and show that forkhead transcription factor Foxc2 controls this process. We further identify transcription factor NFATc1 as a novel regulator of lymphatic development and describe a previously unsuspected link between NFATc1 and Foxc2 in the regulation of lymphatic maturation. We also provide a genome-wide map of FOXC2-binding sites in lymphatic endothelial cells, identify a novel consensus FOXC2 sequence, and show that NFATc1 physically interacts with FOXC2-binding enhancers. These data provide novel insights into the molecular program of lymphatic vascular specification and suggest that FOXC2 and NFATc1 are potential targets for therapeutic intervention.

Involvement of gap junctional intercellular communication in the pathophysiology of inflammation

SUMMARY Inflammation has evolved as a mechanism to defend the body against invading microorganisms and to respond to injury. It requires the coordinated response of a large number of cell types from the whole organism in a time- and space-dependent fashion. This coordination involves several cell-cell communication mechanisms. Exchange of humoral mediators such as cytokines is a major one. Moreover, direct contact between cells happens and plays a primordial role, for example when macrophages present antigens to lymphocytes. Contact between endothelial cells and leucocytes occurs when the latter cross the blood vessel barrier and transmigrate to the inflammatory site. A particular way by which cells communicate with each other in the course of inflammation, which at this time starts to gain attention, is the intercellular communication mediated by gap junctions. Gap junctions are channels providing a direct pathway (i.e. without transit through the extracellular space) for the diffusion of small molecules between adjacent cells. This process is known as gap junctional intercellular communication (GJIC). The general aim of this thesis was to study a possible involvement of GJIC in the pathophysiology of inflammation. A first part of the work was dedicated to study the implication of GJIC in the modification of vascular endothelial function by inflammation. In a second part, we were interested in the possible role of GJIC in the transmigration of neutrophil polymorphonuclear leucocytes through the endothelium. The main positive finding of this work is that acute inflammation preferentially modulates the expression of connexin 40 (Cx40), a gap junction protein specifically expressed in vascular endothelium. The modulation could be towards overexpression (aortic endothelium of septic rats) or towards downregulation (acutely inflamed mouse lung). We put a lot of efforts in search of possible functions of these modulations, in two directions: a potential protective role of Cx40 increased expression against sepsis-induced endothelial dysfunction, and a facilitating role of Cx40 decreased expression in neutrophil transmigration. To pursue both directions, it seemed logical to study the impact of Cx40 deletion using knock-out mice. Concerning the potential protective role of Cx40 overexpression we encountered a roadblock as we observed, in the aorta, a Cx40 downregulation in wild type mouse whereas Cx40 was upregulated in the rat. Regarding the second direction and using an in vivo approach, we observed that pulmonary neutrophil transmigration was not affected by the genetic deletion of Cx40. In spite of their negative nature, these results are the very first ones regarding the potential implication of GJIC concerning leucocyte transmigration in vivo. Because this process involves such tight cell-cell physical contacts, the hypothesis for a role of GJIC remains attractive.

Foam pore size is a critical interface parameter of suction-based wound healing devices.

BACKGROUND: Suction-based wound healing devices with open-pore foam interfaces are widely used to treat complex tissue defects. The impact of changes in physicochemical parameters of the wound interfaces has not been investigated. METHODS: Full-thickness wounds in diabetic mice were treated with occlusive dressing or a suction device with a polyurethane foam interface varying in mean pore size diameter. Wound surface deformation on day 2 was measured on fixed tissues. Histologic cross-sections were analyzed for granulation tissue thickness (hematoxylin and eosin), myofibroblast density (α-smooth muscle actin), blood vessel density (platelet endothelial cell adhesion molecule-1), and cell proliferation (Ki67) on day 7. RESULTS: Polyurethane foam-induced wound surface deformation increased with polyurethane foam pore diameter: 15 percent (small pore size), 60 percent (medium pore size), and 150 percent (large pore size). The extent of wound strain correlated with granulation tissue thickness that increased 1.7-fold in small pore size foam-treated wounds, 2.5-fold in medium pore size foam-treated wounds, and 4.9-fold in large pore size foam-treated wounds (p < 0.05) compared with wounds treated with an occlusive dressing. All polyurethane foams increased the number of myofibroblasts over occlusive dressing, with maximal presence in large pore size foam-treated wounds compared with all other groups (p < 0.05). CONCLUSIONS: The pore size of the interface material of suction devices has a significant impact on the wound healing response. Larger pores increased wound surface strain, tissue growth, and transformation of contractile cells. Modification of the pore size is a powerful approach for meeting biological needs of specific wounds.

Modified Blalock-Taussig shunt with compensatory properties.

Determination of the proper length of the tubular prosthesis is a major issue when performing a systemic-pulmonary artery shunt. The procedure is simplified by using a prosthesis with accordionlike properties. This was demonstrated in 7 consecutive infants with complex congenital heart defects, in whom systemic-pulmonary artery shunts were placed without early or late complications.

eComment: Everyday clinical practice consequences?

Comment on : "Type A aortic dissection involving the carotid arteries: carotid stenting during open aortic arch surgery by Salvatore Lentini, Fabrizio Tancredi, Filippo Benedetto, and Roberto Gaeta in Interactive CardioVascular and Thoracic Surgery 2009 8: 157-159

Optimization and regeneration kinetics of lymphatic-specific photodynamic therapy in the mouse dermis.

Lymphatic vessels transport fluid, antigens, and immune cells to the lymph nodes to orchestrate adaptive immunity and maintain peripheral tolerance. Lymphangiogenesis has been associated with inflammation, cancer metastasis, autoimmunity, tolerance and transplant rejection, and thus, targeted lymphatic ablation is a potential therapeutic strategy for treating or preventing such events. Here we define conditions that lead to specific and local closure of the lymphatic vasculature using photodynamic therapy (PDT). Lymphatic-specific PDT was performed by irradiation of the photosensitizer verteporfin that effectively accumulates within collecting lymphatic vessels after local intradermal injection. We found that anti-lymphatic PDT induced necrosis of endothelial cells and pericytes, which preceded the functional occlusion of lymphatic collectors. This was specific to lymphatic vessels at low verteporfin dose, while higher doses also affected local blood vessels. In contrast, light dose (fluence) did not affect blood vessel perfusion, but did affect regeneration time of occluded lymphatic vessels. Lymphatic vessels eventually regenerated by recanalization of blocked collectors, with a characteristic hyperplasia of peri-lymphatic smooth muscle cells. The restoration of lymphatic function occurred with minimal remodeling of non-lymphatic tissue. Thus, anti-lymphatic PDT allows control of lymphatic ablation and regeneration by alteration of light fluence and photosensitizer dose.