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To our knowledge, the biocompatibility of nickel–titanium (NiTi) single crystals has not been reported. Yet certain orientations of single crystals present several advantages over the polycrystalline form in terms of maximal strain, fatigue resistance, and temperature range of superelasticity. Therefore we tested the in vitro biocompatibility of 50.8% NiTi single crystals in the orientation 〈001〉 after four different heat treatments in a helium atmosphere followed by mechanical polishing. The study was performed on the material extracts after immersion of the specimens in cell culture medium (DMEM) for 7 days at 37°C. Cytotoxicity studies were performed on L-929 mouse fibroblasts using the MTT assay. J-774 macrophages were used to assess the potential inflammatory effect of the extracts by IL1-β and TNF-α dosages (sandwich ELISA method). Exposure of L-929 to material extracts did not affect cell viability. In addition, IL1-β and TNF-α secretion was not stimulated after incubation with NiTi extracts compared to the negative controls. These results were predictable since atomic absorption spectroscopy did not detect nickel ions in the extracts with a resolution of 1 ppm. Within the limits of in vitro testing, our results demonstrate that the TiNi50.8% single crystals do not trigger a cytotoxic reaction. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 641–646, 2003

Catheter-based brachytherapy is one of the most effective modalities to inhibit hyperplasia following revascularization procedures. Radioactive stents have failed, however, to prevent clinical hyperplasia due to excessive late lumen loss on the edge of the devices. Numerous strategies have been proposed to circumvent the drawbacks of irradiation therapies, such as the use of more appropriate radionuclides or the "hot-end" stents approach. This paper describes versatile radioactive devices obtained by coating plasma functionalized surfaces-stents or catheters-with a hyaluronan (HA)-diethylenetriamine pentaacetic acid (DTPA) conjugate (HA-DTPA) complexed with a gamma or beta radionuclide. Yttrium and indium were used as radionuclide models, due to their suitability for endovascular radiotherapy. X-ray photoelectron microscopy and time-of-flight secondary ions mass spectrometry analyses confirmed the successful immobilization of the HA-DTPA conjugate on both the metallic (NiTi) and polymeric (Teflon) plasma functionalized surfaces. HA-DTPA-coated surfaces were significantly more hydrophilic than bare surfaces (39.5 degrees vs. 67 degrees on NiTi substrate and 29 degrees vs. 128 degrees on Teflon substrate). Therapeutic doses of yttrium and indium were easily loaded onto the surfaces and remained stable over 2 weeks with a radionuclide loss of about 6%. The HA-DTPA-coated Teflon surfaces presented significantly less fibrinogen adsorption than uncoated materials in an in vitro flow model. This approach, which combines the hemocompatibility of HA-coated surfaces and the anti-proliferative effects of an appropriate radiotherapy, constitutes a promising methodology to alleviate the restenosis induced by existing devices.

p1⁄40,002), were more likely to have an ambulatory visit rather than a hospitalisation (31% versus 60%, p

Based on promising reports from international randomized trials such as BENESTENT, vascular stent implantation has been increasingly used - with more than 500,000 implantations per year worldwide - and has become a procedure of choice in the treatment of atherosclerotic vascular disease [1,2]. Since the first implantation in 1986, many devices, mostly balloon expandable stainless steel stents, have been approved by regulatory agencies, for both peripheral and coronary revascularization. In the early 90’s, many studies have reported experimental temporary or permanent use of NiTi stents [3,4]. Due to the thermoelastic properties of the alloy, optimal deployment of NiTi self expanding stents can be easily achieved with high expansion ratio and less longitudinal shortening than most common stainless steel devices. In addition, their flexibility and radiopacity along with their good biocompatibility and resistance to corrosion have contributed to their increasing use in cardiovascular applications [5-7]. Despite its good biocompatibility, like all metallic materials NiTi is prone to adsorption of plasma protein such as fibrinogen, which is a potent promoter of platelet adhesion [8]. In a recent study, Makkar et al. have shown that surface topography significantly affects the thrombogenicity of NiTi stents, which may in turn have an effect on complications observed much after implantation [9]. Indeed, platelets adhesion is the first step of thrombus formation which may lead to acute and sub-acute thrombosis. Stent thrombosis still represents a major complication after stent implantation, especially for small vessels, thrombus containing lesions and bifurcation stenoses [10]. Moreover, through the release of growth factor by activated platelets, thrombus formation is expected to participate to the restenosis process initiation [11]. Many strategies have been developed to reduce stents thrombogenicity such as improvement of surface characteristics or coating with pharmacological drugs and polymers [9,12,13].

Platelet-related events being associated with the increment of infarct size at reperfusion in the presence of a residual stenosis, we tested in dogs whether intravenous aspirin (ASA) could limit infarct size. The left anterior descending coronary artery was occluded for 90 min and reperfused for 6 h in the presence of a residual critical stenosis. Controls received saline, and treated groups were given 2, 6, or 12 mg/kg ASA, i.v., 5 min before reperfusion. Infarct size did not differ significantly between groups (control, 43.80 ± 6.28%; ASA, 2 mg/kg: 41.07 ± 7.78%; ASA, 6 mg/kg: 37.55 ± 3.44%; ASA, 12 mg/kg: 29.40 ± 5.41 %), as well as transmural collateral blood flow and [ 111 In]-platelet accumulation in the infarcted myocardium (2.5-3.6 × 10 5 platelets/g). However, myocardial neutrophil accumulation was significantly reduced (p < 0.05) in groups given 6 (15.0 ± 2.6 × 10 6 /g tissue) and 12 mg/kg (18.4 ± 3.8) ASA, but not in the 2-mg/kg group (21.0 ± 5.2), as compared with control group (32.0 ± 7.2). Ex vivo platelet aggregation to collagen was abolished during reperfusion in all treated groups (p < 0.05). Transcardiac arteriovenous differences in 6-keto-PGF 1α were reduced significantly 1 h after reperfusion in groups given 6 or 12 mg/kg ASA (94.7 ± 13.1 and 71.7 ± 19.2 pg/ml, respectively) but not in the 2-mg/kg group (178.3 ± 78.2 pg/ml), as compared with control (405.4 ± 171.6 pg/ml), ASA-insensitive platelet activation at the site of stenosis or inhibition by ASA of prostacyclin production by jeopardized myocardium may explain the observed lack of benefit of ASA.

The selectin family of cell-adhesion molecules contributes to the interactions of leukocytes and platelets at the site of vascular injury. Such interactions enhance inflammatory reactions and thrombus formation during the arterial response to injury. In this study, we investigated the effects of a selectin inhibitor (Fucoidan) on platelet and neutrophil interactions after arterial injury produced by angioplasty in pigs. [ 51 Cr]-platelet deposition and [ 111 In]-neutrophil adhesion were quantified on intact, mildly, and deeply injured carotid arterial segments, produced by balloon dilation in control (saline, n = 7) and Fucoidan-treated (i.v.; 1 mg/kg, n = 6; 5 mg/kg, n = 5) pigs. In the control group, platelet deposition (×10 6 /cm 2 ) was influenced by the severity of injury and increased significantly (p < 0.05) from 0.06 ± 0.06 on intact endothelium to 3.8 ± 0.6 and 33.6 ± 4.9 on mildly and deeply injured segments, respectively. Fucoidan, 1 mg/kg, had no significant effect, although doses of 5 mg/kg reduced platelet deposition by 73% on deeply injured segments. The level of neutrophil adhesion (×10 3 /cm 2 ) was also influenced by the severity of injury: it increased in the control group from 8.8 ± 2.5 on intact endothelium to 226.6 ± 45.5 and 397.4 ± 61.3 on mildly and deeply injured arterial segments, respectively (p < 0.05). Again, 1 mg/kg Fucoidan had no effect, although doses of 5 mg/kg reduced neutrophil adhesion by 92% and by 84% on mildly and deeply injured segments, respectively. The effects of Fucoidan were associated with a 51% decrease in the vasoconstrictive response at the site of arterial injury. However, Fucoidan had no significant effect on either platelet aggregation or activated clotting time (ACT). In the in vitro perfusion experiments, Fucoidan inhibited both isolated platelet, and neutrophil, adhesion to damaged arterial surfaces. This inhibition was more pronounced in experiments using mixed cell preparations, indicating that Fucoidan interferes with platelet and neutrophil interactions. These results highlight the importance of selectins in the acute physiopathologic reactions related to platelet-neutrophil interactions after arterial injury.

Abstract —The adhesion of neutrophils to damaged arterial surfaces is increased in the presence of platelets by a mechanism implicating platelet P-selectin. Such interactions may enhance thrombus formation and the vascular response to injury. In this study, we investigated the effects of a selectin blocker (CY-1503), an analogue of sialyl Lewis x , on platelet and neutrophil interactions after arterial injury produced by angioplasty in pigs. 51 Cr-platelet deposition and 111 In-neutrophil adhesion were quantified on intact, mildly and deeply injured carotid arterial segments, produced by balloon dilation, in control (saline, n=8) and treated (CY-1503, 15 mg/kg IV, n=7) pigs. The hematological parameters, the aggregation of whole blood in response to adenosine diphosphate, and the activating clotting time, as well as the heart rate and mean arterial blood pressure, were similar among groups and were not influenced significantly by CY-1503. The level of platelet and neutrophil adhesion increased significantly with the severity of arterial injury but was not influenced by CY-1503 on intact and mildly injured arterial segments. However, at the site of deep arterial injury, CY-1503 treatment was associated with a 58% reduction ( P 3 neutrophils/cm 2 in the control group to 186.8±38.7×10 3 neutrophils/cm 2 in the CY-1503–treated group, whereas platelet deposition remained unchanged (43.4±15.6×10 6 platelets/cm 2 versus 50.1±12.2×10 6 platelets/cm 2 in the control group). In in vitro adhesion experiments, using isolated platelet and neutrophil suspensions, we found that CY-1503 interfered with the adhesion of neutrophils to damaged arterial surfaces only in the presence of platelets. In contact with thrombogenic arterial surfaces, adherent and activated platelets supports neutrophil adhesion at the site of deep injury by an adhesive interaction involving neutrophil sialyl Lewis x . The inhibitory effect of CY-1503 on neutrophil interaction with adherent platelets may be clinically relevant in patients undergoing percutaneous transluminal coronary angioplasty where platelet and neutrophil interactions may enhance the acute and chronic arterial response to injury.

We compared the effect on platelet deposition of the glycoprotein IIb/IIIa receptor antagonist L-703,081, administered locally via a drug delivery stent, with that of a standard metal stent in a canine coronary model. There was a significant reduction in platelet deposition using the L-703,081-impregnated stent compared with the bare metal stent. This study demonstrates an alternative route of delivery of GPIIb/IIIa antagonists with potential advantages over systemic administration.

We investigated the acute thrombogenicity of synthetic arterial prostheses compared to biological arterial surfaces in contact with flowing nonanticoagulated blood. The acute events following blood/surface interactions were quantified using 51Cr-platelet deposition, 111In-neutrophil adhesion, and 125I-fibrin(ogen) adsorption on expanded polytetrafluoroethylene (ePTFE) synthetic arterial surfaces (Goretex® and Impra®) and on intact and injured biological arterial surfaces in ex vivo superfusion flow chambers at low (424/sec) and high (3397/sec) shear rates for 5 min at 37°C. The hematological parameters were determined, and surface analysis was assessed by scanning electron microscopy. At low shear rate, the retention on intact arterial surfaces averaged 3.7 ± 0.7 × 106 platelets/cm2, 26.5 ± 4.2 × 103 neutrophils/cm2, and 10.7 ± 2.2 cpm of fibrin(ogen)/cm2; retention remained statistically similar at the high shear rate on both Goretex® and Impra® ePTFE surfaces. In contrast, the deposition of platelets and neutrophils on injured arterial surfaces was significantly higher and increased with shear rate, although the significant increase in fibrin(ogen) adsorption was not influenced by the shear rate. At shear rates characterized by patent and stenosed arteries, ePTFE arterial prostheses demonstrated a low level of thrombogenicity compared to injured arteries. This favorable comparison can be considered as the first requirement for their successful use in arterial substitution. © 1997 John Wiley & Sons, Inc.

The deposition of polysaccharide-based self-assembled nanocoatings onto damaged arteries is described as a means not only to protect a damaged artery against thrombogenesis, but also to control the healing processes by incorporating biologically active components within the multilayer. As shown by confocal microscopy, the polysaccharide multilayer was retained on the artery in physiological condition and prevented platelet adhesion. Diffusion of the polysaccharides within the artery was also observed and may be used to efficiently target the vascular wall. The NO-precursor l-arginine was used a drug model and incorporated within the self-assembled layers.

The influence of duration of coronary occlusion and reperfusion on technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-sestamibi) myocardial redistribution between necrotic, salvaged and non-ischaemic myocardium was investigated in dogs submitted either to a 90-min or a 24-h permanent left descending coronary artery occlusion (groups 1 and 2) or to a 90-min occlusion followed by 30 min, 6 h or 22.5 h of reperfusion (groups 3, 4 and 5). In all groups, 99mTc-sesta-mibi and radiolabelled microspheres were injected at 45 min of occlusion. After delimiting the area at risk and the infarct by Evans blue perfusion and triphenyltetrazolium chloride staining, radioactivity of heart slices from normal, viable-ischaemic and necrotic myocardium was measured in a gamma counter. A significant (P

Nitric oxide (NO) synthesized from cultured endothelial cells inhibits platelet aggregation and adhesion to subendothelial extracellular matrix and may contribute to the thromboresistance of the endothelium. NO has also been shown to inhibit neutrophil aggregation and adherence to postcapillary venules. Whether NO derived from the intact endothelium of an arterial wall can influence platelet and neutrophil adhesion under whole-blood arterial flow conditions was evaluated in this study. Porcine aortic segments with intact endothelium were exposed to flowing porcine arterial blood for 5 minutes at a shear rate of 424 sec-1. Pretreatment of the endothelium with the physiological precursor of NO, L-arginine (2 mmol/L), reduced 111In-labeled neutrophil adhesion by 32% from 10.2 +/- 1.6 to 6.9 +/- 1.3 x 10(3)/cm2 (P < .05), relative to control. This effect was reversed by the inhibitor of NO synthesis, N omega-nitro-L-arginine methyl ester (L-NAME, 5 mmol/L) (8.2 +/- 3.0 versus 8.6 +/- 3.2 x 10(3)/cm2 for control; P = NS). Pretreatment of the endothelium with D-arginine (2 mmol/L) did not influence neutrophil adhesion (8.7 +/- 2.0 versus 8.6 +/- 2.0 x 10(3)/cm2 for control; P = NS). The intact endothelium, which is normally thromboresistant, shows a low basal level of 51Cr activity, corresponding to a platelet adhesion less than 0.5 x 10(6)/cm2, and this thromboresistance was not significantly influenced by L-arginine. These results indicate that NO derived from an intact arterial endothelium under whole-blood arterial flow conditions may be an important modulator of neutrophil interaction with the intact endothelium.

Objective: The aim was to investigate the ability of 111In-antimyosin monoclonal antibody (111In-AMA) to differentiate between salvaged and necrotic myocardium following reperfusion. Methods: Dogs submitted to a 24 h left anterior descending coronary artery occlusion (group 1, n= 10) or to a 90 min occlusion followed by a 22.5 h reperfusion (group 2, n=11, group 3, n=5) were given radiolabeled microspheres and 111In-AMA after 75 min of ischaemia (groups 1 and 2), or after 19.5 h of reperfusion (group 3). After delimiting the area at risk and the infarct by dye perfusion and triphenyltetrazolium chloride, the heart slices were imaged by scintigraphy and dissected into necrotic, viable ischaemic, and normal myocardium. Myocardial blood flow was estimated by microspheres and 111In-AMA uptake was expressed as the ratio of the corresponding non-ischaemic tissue samples taken from opposite ventricular wall. Results: 111In-AMA ratios in necrotic and salvaged myocardium were respectively 5.4(SEM 1.9) and 3.2(0.5) times the normal value, giving a 1.7 to 1 factor between the two areas in dogs with permanent occlusion (group 1). Similar results were obtained in group 3 with ratios of 6.1 (1.1) and 3.0(0.3) times normal values. In contrast, ratios of 43.6(5.6) and 5.6(0.9) (p < 0.05) in necrotic and salvaged myocardium, respectively, were found in reperfused group 2, giving a 7.8 to 1 factor between the two tissue areas of the risk territory. Clear delineation between salvaged and necrotic tissue territories could be made on scintigrams only in group 2, which otherwise presented smaller infarcts: 35.1(7.9)% of the risk area v 58.0(8.7)% in non-reperfused animals (p < 0.05). 111In-AMA uptake by necrotic myocardium did not correlate with collateral (group 1) or reperfusion blood flows (group 3), indicating that the greater uptake in reperfused myocardium is flow independent. Conclusions: 111In-AMA does not clearly identify necrotic from viable ischaemic myocardium within 24 h of injection in a coronary artery occlusion model. Thus it may not be a sensitive enough method to evaluate infarct size progression. However, reperfusion greatly increased 111In-AMA uptake by the infarct in a flow independent manner, this may prove to be useful for clinical assessment of infarct size and reperfusion injury. Cardiovascular Research 1993; 27 :1504-1509

Both platelets and neutrophils interact with the injured vessel wall and may contribute to thrombosis and vasospasm. The effect of platelets on neutrophil interactions with the vessel wall was studied in normal and thrombocytopenic pigs. 51Cr-labeled platelet deposition (x10(6)) and 111In-labeled neutrophil deposition (x10(3)) on undamaged aortic strips with intact endothelium or damaged aortic strips with exposed media were quantified in superfusion flow chambers before and after platelet depletion by specific rabbit antisera. Arterial blood was drawn at a constant flow rate through the superfusion chambers at 37 degrees C. Under basal conditions, platelets did not adhere to the uninjured vessel wall with intact endothelium, whereas neutrophil interaction with the endothelium was low and constant at shear rates of 427, 853, and 1280 s-1 and did not change significantly after thrombocytopenia. On exposed aortic media simulating deep arterial injury, platelet deposition increased over these shear rates from 14.0 +/- 3.4 to 37.5 +/- 12.0 (P < .05) to 68.0 +/- 9.0, respectively (P < .05). Similarly, neutrophil deposition on the media increased from 48.7 +/- 8.7 to 73.7 +/- 14.3 (P < .05) to 118.3 +/- 22.9, respectively (P < .05). Platelet deposition on the media did not occur after thrombocytopenia (80% reduction in platelet count); however, neutrophil deposition persisted, but was less intense and was now independent of shear rates (23.3 +/- 5.2 at 427 s-1, 18.7 +/- 3.2 at 853 s-1, and 24.1 +/- 3.9 at 1280 s-1; not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Technetium-99m hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) distribution is flow-dependent, permitting the imaging of coronary perfusion defects. However, the behaviour of this tracer in viable and necrotic tissues within the ischaemic area at risk is still being debated. In a clinically relevant canine model, dogs were submitted either to a 24-h permanent occlusion (group 1) of the left descending coronary artery (LAD) or to a 90-min LAD occlusion followed by 22.5 h reperfusion (group 2). 99mTc-MIBI and radiolabelled microspheres were injected 3 h before sacrifice. After delimiting the area at risk and the infarct by Evans blue perfusion and triphenyltetrazolium chloride staining, heart slices were imaged by scintigraphy and tissue radioactivity measured in a gamma-counter. In the necrotic area of both groups, the 99mTc-MIBI distribution was proportional to the myocardial blood flow, approximating a 1:1 ratio (identity line slope l, intercept 0) with highly significant correlation coefficients (group 1 r = 0.87, group 2 r = 0.86), whereas in the viable-ischaemic area of both groups, the data points are widespread above and below the identity line, indicating both over- and underestimations of blood flow in these tissue areas. These results were more pronounced following reperfusion as compared with permanent occlusion. Multiple linear regression analysis confirms differences (P < 0.001) in 99Tc-MIBI distributions between the viable-ischaemic and the necrotic zones. Delineation of the ischaemic area at risk was possible only with permanent occlusion. A hypoper-fused area was observed after reperfusion but differs from the anatomical infarcted area. These results indicate that the 99mTc-MIBI distribution is not significantly influenced by myocardial cell death, whereas the relationship of 99mTc-MIBI to blood flow in the remaining viable-ischaemic myocardium salvaged by reperfusion appears more deeply affected. Therefore, the influence of tissue viability on the 99mTc-MIBI distribution in the myocardium must be reconsidered in the light of these observations.

Corpora amylacea (CA) accumulation in the brain is a normal correlate of ageing. The presence of a small amount of protein in these polyglucosan bodies is a consistent finding, although the nature of this protein material remains unknown. Using sucrose gradient fractionation and density centrifugation on Percoll, a method was developed to obtain highly pure preparations of CA from human brain. The protein content of isolated CA was estimated to be approx. 4% of the total fraction by weight. SDS-PAGE analysis of CA fractions showed several polypeptide bands with molecular weights ranging from 24 to 133 kDa. Four of these bands with molecular weights of 133, 94, 42 and 24 kDa are more abundant. Thus, pure preparations of CA can be obtained that are suitable for protein analysis.

Preclotting is mandatory prior to implanting a knitted polyester arterial graft, unless the structure is made impermeable to blood by coating with a bioerodible material. Before achieving wide-spread clinical acceptance, the technique of impregnating with cross-linked albumin must be optimized in order to develop a graft that is immediately implantable, easy to handle and suture and has improved healing characteristics. The choice of the chemical to cross-link the albumin is of paramount importance. In this study two alternative candidates have been evaluated by using a series of tests to measure the physical properties, the morphology and the cytocompatibility of albumin-coated grafts. A carbodiimide cross-linking agent appears more promising than glutaraldehyde, since it is equally effective in producing a blood impermeable prosthesis, yet presents improved biocompatibility and provokes a less intense inflammatory response from the host.

The concept of polyester arterial grafts impregnated with a bioerodible coating is now widely accepted as worthy of investigation. Gelatin- and collagen-coated grafts are commercially available, ready to anastomose and thus do not require any processing in the operating room. The albumin-coated graft (ACG), a Vasculour ll impregnated with albumin now being introduced by Bard Cardiosurgery, does not require rehydration or rinsing. We hereby report its in vitro evaluation in terms of biodegradability of the coating and physical characteristics. When measuring the blood permeability, one can observe that the wall is made impervious in the case of crosslinked albumin impregnation after one minute, yet it requires approximately three minutes after preclotting to make the wall blood-tight.

Two collagen-coated grafts were studied: Hemashield® (bovine collagen cross-linked with formaldehyde vapours and softened by exposure to glycerol) and Tascon® (collagen fibres cross-linked with glutaraldehyde solution). The weight of the coating was 310 ± 5 mg / g for Hemashield® and 45 ± 2.5 mg / g for Tascon®. However, notwithstanding these differences, both coatings were efficient in making the walls of the grafts impervious to blood. The water permeabilities for the Hemashield® and the Tascon® were 8.7 and 5.9 ml.min −1 .cm −2 at 120 mmHg respectively. The Hemashield® collagen coating was rapidly eroded in vitro (4 h) after exposure to buffer, trypsin or pancreatin solutions, whereas the Tascon® collagen coating remained well preserved after 7 d incubation. Both coatings were safe and did not interfere with the physical properties of the graft which was used as a skeleton. The healing properties of the Hemashield® were similar to that observed with preclotted polyester prostheses, except in the early hours following graft implantation. On the other hand, the absence of erosion in the coating of the Tascon® seemed to contribute to early antithrombogenicity. It also induced marked inflammatory reactions in the surrounding tissues and thus the healing appeared to be delayed.

Previous in vitro studies have predicted that the type of chemical used to cross-link albumin-coated polyester arterial prostheses may influence the rate of bioerosion of the albumin layer in vivo. This study has confirmed that the healing process of this type of compound prosthesis does indeed depend on the nature and concentration of the cross-linking agent used. Four series of implantations in the thoracic aorta of dogs for scheduled periods for 4 h up to 6 months were conducted using 1.6% glutaraldehyde, 2.5% glutaraldehyde and 0.2 M carbodiimide as the alternative cross-linking agents plus a nonalbuminated preclotted polyester prosthesis which served as the control. The pathology of the explanted grafts revealed that in the short and medium term the rate of healing and the extent of tissue ingrowth was dependent initially on the presence of and later on the rate of bioerosion of the albumin layer. After 3 months in situ, the prostheses coated with albumin cross-linked with 1.6% glutaraldehyde and carbodiimide had healed more rapidly and were invaded by more extensive tissue ingrowth than the one cross-linked with 2.5% glutaraldehyde or the preclotted control. Moreover, the migration of cells over the carbodiimide-treated surface was the most fully developed and most regularly organized of all four series. Immunostaining revealed that the presence of glutaraldehyde induced an inflammatory response which failed to support the growth of normal luminal cells with the endothelial phenotype.

Over the years, textile polyester arterial prostheses have acquired an excellent reputation for easy handling and good healing characteristics. Until recently, the main drawback in using them was the need for preclotting. This, however, is no longer true. Nonporous polyester grafts which have been coated with an impervious bioerodible layer during manufacture are now commercially available. The Gelseal Triaxial prosthesis is one of this new generation of grafts. It is manufactured by impregnating a Triaxial prosthesis with a gelatin coating. An in vivo and in vitro evaluation of this new device has found that its water permeability is almost zero. It has good handling and conformability characteristics, and its bursting strength is slightly greater than that of the uncoated prosthesis due, no doubt, to the presence of the gel. The rates of degradation of the gelatin coating have proven to be rapid under both in vitro and in vivo conditions. In fact, only a few traces of the gel were found remaining on the graft after 2 wk in the canine thoracic aorta. In addition, this study has demonstrated that the use of a bioerodible gelatin coating, with its ability to promote cellular regeneration, is a feasible approach with which to achieve earlier and more complete biological healing.

This paper adds a new dimension to the series of studies concerned with the development of an albumin-coated polyester vascular prosthesis by addressing the question of the origin of the albumin. Previous experiments in dogs have used canine albumin-coated polyester arterial grafts. This study evaluated the biocompatibility of xenogenic material by implanting in dogs prostheses coated with bovine albumin and cross-linked with glutaraldehyde. Two series of albuminated grafts, one gamma radiation sterilized, the other ethylene oxide sterilized, as well as a preclotted control series were undertaken. The origin of the albumin did not appear to be significant. In fact, the healing pattern of the xenogenic albumin coated grafts was identical to that found previously with isogenic albumin. Nor did the method of sterilization produce significantly different pathological results. However, a slower rate of healing with the coated grafts compared to the preclotted controls did appear to be related to the slow rate of albumin erosion and the potentially cytotoxic effect of the glutaraldehyde cross-linking agent.

Background Endothelial progenitor cells (EPCs) have been implicated in neoangiogenesis, endothelial repair and cell-based therapies for cardiovascular diseases. We have previously shown that the recruitment of EPCs to sites of vascular lesions is facilitated by platelets where EPCs, in turn, modulate platelet function and thrombosis. However, EPCs encompass a heterogeneous population of progenitor cells that may exert different effects on platelet function. Recent evidence suggests the existence of two EPC subtypes: early outgrowth cells (EOCs) and endothelial colony-forming cells (ECFCs). We aimed at characterizing these two EPC subtypes and at identifying their role in platelet aggregation. Methods EOCs and ECFCs were generated from human peripheral blood mononuclear cells (PBMCs) seeded in conditioned media on fibronectin and collagen, respectively. The morphological, phenotypical and functional characteristics of EOCs and ECFCs were assessed by optical and confocal laser scanning microscopes, cell surface markers expression, and Matrigel tube formation. The impact of EOCs and ECFCs on platelet aggregation was monitored in collagen-induced optical aggregometry and compared with PBMCs and human umbilical vein endothelial cells (HUVECs). The levels of the anti-platelet agents’ nitric oxide (NO) and prostacyclin (PGI2) released from cultured cells as well as the expression of their respective producing enzymes NO synthases (NOS) and cyclooxygenases (COX) were also assessed. Results We showed that EOCs display a monocytic-like phenotype whereas ECFCs have an endothelial-like phenotype. We demonstrated that both EOCs and ECFCs and their supernatants inhibited platelet aggregation; however ECFCs were more efficient than EOCs. This could be related to the release of significantly higher amounts of NO and PGI2 from ECFCs, in comparison to EOCs. Indeed, ECFCs, like HUVECs, constitutively express the endothelial (eNOS)—and inducible (iNOS)—NOS isoforms, and COX-1 and weakly express COX-2, whereas EOCs do not constitutively express these NO and PGI2 producing enzymes. Conclusion The different morphological, phenotypic and more importantly the release of the anti-aggregating agents PGI2 and NO in each EPC subtype are implicated in their respective roles in platelet function and thus, may be linked to the increased efficiency of ECFCs in inhibiting platelet aggregation as compared to EOCs.

Background The role of endothelial progenitor cells (EPCs) in vascular repair is related to their recruitment at the sites of injury and their interaction with different components of the circulatory system. We have previously shown that EPCs bind and inhibit platelet function and impair thrombus formation via prostacyclin secretion, but the role of EPC binding to platelet P-selectin in this process has not been fully characterized. In the present study, we assessed the impact of EPCs on thrombus formation and we addressed the implication of P-selectin in this process. Methods EPCs were generated from human peripheral blood mononuclear cells cultured on fibronectin in conditioned media. The impact of EPCs on platelet aggregation and thrombus formation was investigated in P-selectin deficient (P-sel−/−) mice and their wild-type (WT) counterparts. Results EPCs significantly and dose-dependently impaired collagen-induced whole blood platelet aggregation in WT mice, whereas no effects were observed in P-sel−/− mice. Moreover, in a ferric chloride-induced arterial thrombosis model, infusion of EPCs significantly reduced thrombus formation in WT, but not in P-sel−/− mice. Furthermore, the relative mass of thrombi generated in EPC-treated P-sel−/− mice were significantly larger than those in EPC-treated WT mice, and the number of EPCs recruited within the thrombi and along the arterial wall was reduced in P-sel−/− mice as compared to WT mice. Conclusion This study shows that EPCs impair platelet aggregation and reduce thrombus formation via a cellular mechanism involving binding to platelet P-selectin. These findings add new insights into the role of EPC-platelet interactions in the regulation of thrombotic events during vascular repair.