Femoral blood gas analysis, another tool to assess hemorrhage severity following trauma: an exploratory prospective study.

BACKGROUND: Veno-arterial carbon dioxide tension difference (ΔPCO2) and mixed venous oxygen saturation (SvO2) have been shown to be markers of the adequacy between cardiac output and metabolic needs in critical care patients. However, they have hardly been assessed in trauma patients. We hypothesized that femoral ΔPCO2 (ΔPCO2 fem) and SvO2 (SvO2 fem) could predict the need for red blood cell (RBC) transfusion following severe trauma. METHODS: We conducted a prospective and observational study in a French level I trauma center. Patients admitted to the trauma room following severe trauma with an Injury Severity Score (ISS) > 15, who had arterial and venous femoral catheters inserted were included. ΔPCO2 fem, SvO2 fem and arterial blood lactate were measured over the first 24 h of admission. Their abilities to predict the transfusion of at least one pack of RBC (pRBCH6) or hemostatic procedure during the first six hours of admission were assessed using receiver operating characteristics curve. RESULTS: 59 trauma patients were included in the study. Median ISS was 26 (22-32). 28 patients (47%) received at least one pRBCH6 and 21 patients (35,6%) had a hemostatic procedure performed during the first six hours of admission. At admission, ΔPCO2 fem was 9.1 ± 6.0 mmHg, SvO2 fem 61.5 ± 21.6% and blood lactate was 2.7 ± 1.9 mmol/l. ΔPCO2 fem was significantly higher (11.6 ± 7.1 mmHg vs. 6.8 ± 3.7 mmHg, P = 0.003) and SvO2 fem was significantly lower (50 ± 23 mmHg vs. 71.8 ± 14.1 mmHg, P < 0.001) in patients who were transfused than in those who were not transfused. Best thresholds to predict pRBCH6 were 8.1 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Best thresholds to predict the need for a hemostatic procedure were 5.9 mmHg for ΔPCO2 fem and 63% for SvO2 fem. Blood lactate was not predictive of pRBCH6 or the need for a hemostatic procedure. CONCLUSION: In severe trauma patients, ΔPCO2 fem and SvO2 fem at admission were predictive for the need of RBC transfusion and hemostatic procedures during the first six hours of management while admission lactate was not. ΔPCO2 fem and SvO2 fem appear thus to be more sensitive to blood loss than blood lactate in trauma patients, which might be of importance to early assess the adequation of tissue blood flow with metabolic needs.

The intake of flavonoids, stilbenes, and tyrosols, mainly consumed through red wine and virgin olive oil, is associated with lower carotid and femoral subclinical atherosclerosis and coronary calcium.

PURPOSE: It is suggested that polyphenols back the cardiovascular protection offered by the Mediterranean diet. This study evaluates the association of specific types of dietary polyphenols with prevalent subclinical atherosclerosis in middle-aged subjects. METHODS: Ultrasonography and TC were performed on 2318 men from the Aragon Workers Health Study, recruited between 2011 and 2014, to assess the presence of plaques in carotid and femoral arteries and coronary calcium. Polyphenol intake was assessed using a validated semi-quantitative 136-item food frequency questionnaire. The Phenol Explorer database was used to derive polyphenol class intake. Logistic and linear regressions were used to estimate the cross-sectional association of polyphenols intake with femoral and carotid subclinical atherosclerosis and coronary calcium. RESULTS: A higher intake of flavonoids (third vs. first tertile) was associated with a lower risk of both carotid (OR 0.80: CI 95% 0.62-1.02; P trend 0.094) and femoral (0.62: 0.48-0.80, P trend < 0.001) subclinical atherosclerosis. A higher intake of stilbenes was associated with a lower risk of femoral subclinical atherosclerosis (0.62: 0.46-0.83; P trend 0.009) and positive coronary calcium (0.75: 0.55-1.03; P trend 0.131). A higher intake of tyrosols was also associated with a lower risk of positive coronary calcium (0.80: 0.62-1.03; P trend 0.111). The associations remained similar when adjusted for blood lipids and blood pressure. CONCLUSION: Dietary flavonoids, stilbenes, and tyrosols, whose main sources are red wine and virgin olive oil, are associated with lower prevalence of subclinical atherosclerosis in middle-aged subjects.

Performance of PEGylated chitosan and poly (L-lactic acid-co-ε-caprolactone) bilayer vascular grafts in a canine femoral artery model.

The fabrication of a functional small-diameter vascular graft with good biocompatibility, in particular hemocompatibility, has become an urgent clinical necessity. We fabricated a native bilayer, small-diameter vascular graft using PEGylated chitosan (PEG-CS) and poly (L-lactic acid-co-ε-caprolactone; PLCL). To stabilize the inner layer, a PEG-CS blend with PLCL at ratio of 1:6 was casted on a round metal bar by a drip feed, and the outer layer, a PLCL blend with water-soluble PEG that acted as a sacrificial part to enhance pore size, was fabricated by electrospinning. The results showed excellent hemocompatibility and strong mechanical properties. In vitro, the degradation of the graft was evaluated by measuring the graft structure, mass loss rate, and changes in molecular weight. The results indicated that the graft had adequate support for the regeneration of blood vessels before collapse. An in vivo study was performed in a canine femoral artery model for up to 24 weeks, which demonstrated that the PEGylated bilayer grafts possessed excellent structural integrity, high compatibility with blood, good endothelial cell (EC) and smooth muscle cell (SMC) growth, and high expression levels of angiogenesis-related proteins, features that are highly similar to autologous blood vessels. Moreover, the results showed almost negligible calcification within 24 weeks. These findings confirm that the bilayer graft mimics native cells, thereby effectively improving vascular remodeling.

Histological features of restenosis associated with paclitaxel drug-coated balloon: implications for therapy.

PURPOSE: To investigate the cellular and extracellular changes induced by drug-coated balloons (DCB) in the treatment of superficial femoral artery (SFA) restenosis, and to compare histopathological features with those observed after plain old balloon angioplasty (POBA) from the same patients. METHODS AND RESULTS: Plaque samples for five patients with SFA restenosis (first-time) after POBA were collected using atherectomy and DCB. These samples constitute the POBA restenosis group. The same five patients developed recurrent restenosis (RR) after DCB, at the same intervention site. These SFA-RR lesions were again treated using atherectomy and POBA. These samples constitute the DCB restenosis group. DCB restenosis group plaques showed significant reduction in neointima, smooth muscle cells, fibroblast densities, and Ki67 index; and increase in caspase 3, features of apoptosis and type III collagen deposition in comparison to the POBA restenosis group. CONCLUSION: Plaque tissue from the DCB restenosis group show reductions in neointimal thickness, cellularity, and cellular proliferation, along with increased apoptosis, and Type III collagen content. These results suggest a different mechanistic pathway for DCB restenosis, in which neointimal proliferation is reduced but reparative fibrosis is increased. The treatment for SFA-RR after DCB may therefore benefit from different forms of therapy including scaffolding, rather than recurrent anti-proliferative therapy.

Incremental effects of diabetes mellitus and chronic kidney disease in medial arterial calcification: Synergistic pathways for peripheral artery disease progression.

Diabetes mellitus (DM) and chronic kidney disease (CKD) separately are known to facilitate the progression of medial arterial calcification (MAC) in patients with symptomatic peripheral artery disease (PAD), but their combined effect on MAC and associated mediators of calcification is not well studied. The association of MAC and calcification inducer bone morphogenetic protein (BMP-2) and inhibitor fetuin-A, with PAD, is well known. Our aim was to investigate the association of MAC with alterations in BMP-2 and fetuin-A protein expression in patients with PAD with DM and/or CKD. Peripheral artery plaques (50) collected during directional atherectomy from symptomatic patients with PAD were evaluated, grouped into no-DM/no-CKD (n = 14), DM alone (n = 10), CKD alone (n = 12), and DM+CKD (n = 14). MAC density was evaluated using hematoxylin and eosin, and alizarin red stain. Analysis of inflammation, neovascularization, BMP-2 and fetuin-A protein density was performed by immunohistochemistry. MAC density, inflammation grade and neovessel content were significantly higher in DM+CKD versus no-DM/no-CKD and CKD (p < 0.01). BMP-2 protein density was significantly higher in DM+CKD versus all other groups (p < 0.01), whereas fetuin-A protein density was significantly lower in DM+CKD versus all other groups (p < 0.001). The combined presence of DM+CKD may be associated with MAC severity in PAD plaques more so than DM or CKD alone, as illustrated in this study, where levels of calcification mediators BMP-2 and fetuin-A protein were related most robustly to DM+CKD. Further understanding of mechanisms involved in mediating calcification and their association with DM and CKD may be useful in improving management and developing therapeutic interventions.

Primary angiosarcoma of the femoral artery in patient with kidney and liver polycystosis and multiple arterial aneurysms: report of the case and review of the literature.

The association between kidney and liver polycystosis and arterial aneurysms is well documented. However, it remains unclear whether these patients are at increased risk of malignant transformation. In this article, we describe a case of a primary angiosarcoma of the femoral artery with metastatic spread into the lungs and hilar lymph node arising in a 74-year-old man with kidney and liver polycystosis and multiple arterial aneurysms.

Assessment of extracellular matrix-related biomarkers in patients with lower extremity artery disease.

BACKGROUND: The prevalence of lower extremity artery disease (LEAD) is high (20%-25%) in the population older than 65 years, but patients are seldom identified until the disease is advanced. Circulating markers of disease activity might provide patients with a key opportunity for timely treatment. We tested the hypothesis that measuring blood-specific fragments generated during degradation of the extracellular matrix (ECM) could provide further insight into the pathophysiologic mechanism of arterial remodeling. METHODS: The protein profile of diseased arteries from patients undergoing infrainguinal limb revascularization was assessed by a liquid chromatography and tandem mass spectrometry, nontargeted proteomic approach. The information retrieved was the basis for measurement of neoepitope fragments of ECM proteins in the blood of 195 consecutive patients with LEAD by specific enzyme-linked immunosorbent assays. RESULTS: Histologic and proteomic analyses confirmed the structural disorganization of affected arteries. Fourteen of 81 proteins were identified as differentially expressed in diseased arteries with respect to healthy tissues. Most of them were related to ECM components, and the difference in expression was used in multivariate analyses to establish that severe arterial lesions in LEAD patients have a specific proteome. Analysis of neoepitope fragments in blood revealed that fragments of versican and collagen type IV, alone or in combination, segregated patients with mild to moderate symptoms (intermittent claudication, Fontaine I-II) from those with severe LEAD (critical limb ischemia, Fontaine III-IV). CONCLUSIONS: We propose noninvasive candidate biomarkers with the ability to be clinically useful across the LEAD spectrum.

Determination of residual dimethylsulfoxide in cryopreserved cardiovascular allografts.

Dimethylsulfoxide (DMSO) is a solvent which protects the structure of allografts during the cryopreservation and thawing process. However, several toxic effects of DMSO in patients after transplantation of cryopreserved allografts have been described. The aim of this study is to determine the residual DMSO in the cardiovascular allografts after thawing and preparation of cryopreserved allografts for clinical application following guidelines of the European Pharmacopoeia for DMSO detection. Four types of EHB allografts (aortic valve-AV, pulmonary valve-PV, descending thoracic aorta-DA, and femoral artery-FA) are cryopreserved using as cryoprotecting solution a 10% of DMSO in medium 199. Sampling is carried out after thawing, after DMSO dilution and after delay of 30 min from final dilution (estimated delay until allograft implantation). After progressive thawing in sterile water bath at 37-42 °C (duration of about 20 min), DMSO dilution is carried out by adding consecutively 33, 66 and 200 mL of saline. Finally, tissues are transferred into 200 mL of a new physiologic solution. Allograft samples are analysed for determination of the residual DSMO concentration using a validated Gas Chromatography analysis. Femoral arteries showed the most important DMSO reduction after the estimated delay: 92.97% of decrease in the cryoprotectant final amount while a final reduction of 72.30, 72.04 and 76.29% in DMSO content for AV, PV and DA, was found, respectively. The residual DMSO in the allografts at the moment of implantation represents a final dose of 1.95, 1.06, 1.74 and 0.26 mg kg-1 in AV, PV, DA and FA, respectively, for men, and 2.43, 1.33, 2.17 and 0.33 mg kg-1 for same tissues for women (average weight of 75 kg in men, and 60 kg in women). These results are seriously below the maximum recommended dose of 1 g DMSO kg-1 (Regan et al. in Transfusion 50:2670-2675, 2010) of weight of the patient guaranteeing the safety and quality of allografts.

Time-dependent differences in femoral artery plaque characteristics of peripheral arterial disease patients.

BACKGROUND AND AIMS: Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis with an increasing incidence worldwide. The disease is still associated with high morbidity and mortality risks. Previous research in carotid arteries indicates that atherosclerotic plaque characteristics have stabilized over time in patients considered for surgery. It is currently unknown whether this time-dependent stabilization occurs in ilio-femoral arteries as well. Our objective was to analyze whether local ilio-femoral atherosclerotic plaque characteristics have changed over time. METHODS: 497 patients within the Athero-Express biobank who underwent primary endarterectomy of the iliac or femoral artery between 2002 and 2013 were analyzed. We investigated six histological plaque characteristics: calcification, collagen, fat content, intraplaque haemorrhage, macrophages and smooth muscle cells. RESULTS: Over the course of 10 years, we observed a lower percentage of all plaque characteristics that are considered indicators of a vulnerable plaque, such as: plaques with a large lipid core from 37.9% to 14.9% and plaques with intraplaque haemorrhage from 69.0% to 34.8% when the two-year cohorts 2003-2004 and 2011-2012 were compared, respectively. Multivariable analyses showed that time-dependent changes occurred independently of changing procedural and patient characteristics. CONCLUSIONS: In this cohort of peripheral arterial disease patients undergoing primary endarterectomy, we observed a time dependent shift of plaque characteristics towards a less lipid rich lesion with less intraplaque haemorrhage. These findings indicate research in cardiovascular disease would benefit from contemporary patient characteristics and plaque specimens to optimize translational potential.

Talin and vinculin are downregulated in atherosclerotic plaque; Tampere Vascular Study.

BACKGROUND AND AIMS: Focal adhesions (FA) play an important role in the tissue remodeling and in the maintenance of tissue integrity and homeostasis. Talin and vinculin proteins are among the major constituents of FAs contributing to cellular well-being and intercellular communication. METHODS: Microarray analysis (MA) and qRT-PCR low-density array were implemented to analyze talin-1, talin-2, meta-vinculin and vinculin gene expression in circulating blood and arterial plaque. RESULTS: All analyzed genes were significantly and consistently downregulated in plaques (carotid, abdominal aortic and femoral regions) compared to left internal thoracic artery (LITA) control. The use of LITA samples as controls for arterial plaque samples was validated using immunohistochemistry by comparing LITA samples with healthy arterial samples from a cadaver. Even though the differences in expression levels between stable and unstable plaques were not statistically significant, we observed further negative tendency in the expression in unstable atherosclerotic plaques. The confocal tissue imaging revealed gradient of talin-1 expression in plaque with reduction close to the vessel lumen. Similar gradient was observed for talin-2 expression in LITA controls but was not detected in plaques. This suggests that impaired tissue mechanostability affects the tissue remodeling and healing capabilities leading to development of unstable plaques. CONCLUSIONS: The central role of talin and vinculin in cell adhesions suggests that the disintegration of the tissue in atherosclerosis could be partially driven by downregulation of these genes, leading to loosening of cell-ECM interactions and remodeling of the tissue.

Invasive evaluation of plaque morphology of symptomatic superficial femoral artery stenoses using combined near-infrared spectroscopy and intravascular ultrasound.

The purpose of this study is to characterize the plaque morphology of severe stenoses in the superficial femoral artery (SFA) employing combined near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS). Atherosclerosis is the most common cause of symptomatic peripheral arterial disease. Plaque composition of SFA stenoses has been characterized as primarily fibrous or fibrocalcific by non-invasive and autopsy studies. NIRS has been validated to detect lipid-core plaque (LCP) in the coronary circulation. We imaged severe SFA stenoses with NIRS-IVUS prior to revascularization in 31 patients (46 stenoses) with Rutherford claudication ⩾ class 3. Angiographic parameters included lesion location and stenosis severity. IVUS parameters included plaque burden and presence of calcium. NIRS images were analyzed for LCP and maximum lipid-core burden index in a 4-mm length of artery (maxLCBI4mm). By angiography, 38 (82.6%) lesions were calcified and 9 (19.6%) were chronic total occlusions. Baseline stenosis severity and lesion length were 86.0 ± 11.0% and 36.5 ± 46.5 mm, respectively. NIRS-IVUS identified calcium in 45 (97.8%) lesions and LCP in 17 (37.0%) lesions. MaxLCBI4mm was 433 ± 244. All lesions with LCP also contained calcium; there were no non-calcified lesions with LCP. In conclusion, this is the first study of combined NIRS-IVUS in patients with PAD. NIRS-IVUS demonstrates that nearly all patients with symptomatic severe SFA disease have fibrocalcific plaque, and one-third of such lesions contain LCP. These findings contrast with those in patients with acute coronary syndromes, and may have implications regarding the pathophysiology of atherosclerosis in different vascular beds.

Eldecalcitol prevents endothelial dysfunction in postmenopausal osteoporosis model rats.

Postmenopausal women have high incidence of cardiovascular events as estrogen deficiency can cause endothelial dysfunction. Vitamin D is reported to be beneficial on endothelial function, but it remains controversial whether vitamin D is effective for endothelial dysfunction under the treatment for osteoporosis in postmenopausal women. The aim of this study was to evaluate the endothelial protective effect of eldecalcitol (ELD) in ovariectomized (OVX) rats. ELD (20  ng/kg) was orally administrated five times a week for 4 weeks from 1 day after surgery. After that, flow-mediated dilation (FMD) as an indicator of endothelial function was measured by high-resolution ultrasound in the femoral artery of living rats. ELD ameliorated the reduction of FMD in OVX rats. ELD inhibited the increase in NOX4, nitrotyrosine, and p65 and the decrease in dimer/monomer ratio of nitric oxide synthase in OVX rat femoral arteries. ELD also prevented the decrease in peroxisome proliferator-activated receptor gamma (PPARγ) in femoral arteries and cultured endothelial cells. Although PPARγ is known to inhibit osteoblastogenesis, ELD understandably increased bone mineral density of OVX rats without increase in PPARγ in bone marrow. These results suggest that ELD prevented the deterioration of endothelial function under condition of preventing bone loss in OVX rats. This endothelial protective effect of ELD might be exerted through improvement of endothelial nitric oxide synthase uncoupling, which is mediated by an antioxidative effect through normalization of vascular PPARγ/NF-κB signaling.

Kindlin 3 (FERMT3) is associated with unstable atherosclerotic plaques, anti-inflammatory type II macrophages and upregulation of beta-2 integrins in all major arterial beds.

BACKGROUND: Kindlins (FERMT) are cytoplasmic proteins required for integrin (ITG) activation, leukocyte transmigration, platelet aggregation and thrombosis. Characterization of kindlins and their association with atherosclerotic plaques in human(s) is lacking. METHODS AND RESULTS: Exploratory microarray (MA) was first performed followed by selective quantitative validation of robustly expressed genes with qRT-PCR low-density array (LDA). In LDA, ITGA1 (1.30-fold, p = 0.041) and ITGB3 (1.37-fold, p = 0.036) were upregulated in whole blood samples of patients with coronary artery disease (CAD) compared to healthy controls. In arterial plaques, both robustly expressed transcript variants of FERMT3 (MA: 5.90- and 3.4-fold; LDA: 3.99-fold, p < 0.0001 for all) and ITGB2 (MA: 4.81- and 4.92-fold; LDA: 5.29-fold, p < 0.0001 for all) were upregulated while FERMT2 was downregulated (MA: -1.61-fold; LDA: -2.88-fold, p < 0.0001 for both). The other integrins (ITGA1, ITGAV, ITGB3, ITGB5) were downregulated. All these results were replicated in at least one arterial bed. The latter FERMT3 transcript variant associated with unstable plaques (p = 0.0004). FERMT3 correlated with M2 macrophage markers and in hierarchical cluster analysis clustered with inflammatory and macrophage markers, while FERMT2 correlated with SMC-rich plaque markers and clustered with SMC markers. In confocal immunofluorescence analysis, FERMT3 protein colocalized with abundant CD68-positive cells of monocytic origin in the atherosclerotic plaques, while co-localization of FERMT3 with HHF35 indicative of smooth muscle cells was low. CONCLUSIONS: Kindlin-3 (FERMT3) is upregulated in atherosclerotic, especially unstable plaques, mainly in cells of monocytic origin and of M2 type. Simultaneous upregulation of ITGB2 suggests a synergistic effect on leukocyte adherence and transmigration into the vessel wall.

Role of TGF-ß Signaling in Remodeling of Noncoronary Artery Aneurysms in Kawasaki Disease.

Coronary artery aneurysms (CAA) remain an important complication of Kawasaki disease (KD), the most common form of pediatric acquired heart disease in developed countries. Potentially life-threatening CAA develop in 25% of untreated children and 5% of children treated with high-dose intravenous immunoglobulin during the acute phase of the self-limited vasculitis. Noncoronary artery aneurysms (NCAA) in extraparenchymal, muscular arteries occur in a minority of patients with KD who also have CAA, yet little is understood about their formation and remodeling. We postulated that activation of the transforming growth factor-ß (TGF-ß) pathway in KD may influence formation and remodeling of aneurysms in iliac, femoral, and axillary arteries, the most common sites for NCAA. We studied a resected axillary artery from one adult and endarterectomy tissue from the femoral artery from a second adult, both with a history of CAA and NCAA following KD in infancy. Histology of the axillary artery aneurysm revealed destruction of the internal elastic lamina and recanalization of organized thrombus, while the endarterectomy specimen showed dense calcification and luminal myofibroblastic proliferation. Immunohistochemistry for molecules in the TGF-ß signaling pathway revealed increased expression of TGF-ß2, TGF-ß receptor 2, and phosphorylated SMAD3. These findings suggest ongoing tissue remodeling of the aneurysms decades after the acute injury and demonstrate the importance of the TGF-ß signaling pathway in this process.

Proangiogenic potency of MUC18 in arteriosclerotic disease.

AIM: Stenotic peripheral and dilatative arteriosclerotic diseases have different pathomechanism although associations between both diseases are well known. The adhesion molecule MUC18 is a cell membrane glycoprotein also known as the melanoma cell adhesion molecule. As MUC18 has proangiogenic potency in melanoma and prostate cancer this study investigated the role of MUC18 in patients with stenotic or dilatative arteriosclerotic disease as a putative biochemical marker. METHODS: Using qRT-PCR, Western Blot and immunohistochemistry techniques, the expression of MUC18 in arteriosclerotic arteries from major lower limb amputates (AP, N.=15) as well as specimen from femoral endarterectomies (TEA, N.=20) and in dilatative aortic diseases using abdominal aortic aneurysms (AAA, N.=13) was evaluated. Human visceral arteries without macroscopic arteriosclerosis from liver transplants served as controls (AN, N.=19). RESULTS: MUC18 mRNA and protein expression could be found in AN, AP, TEA and AAA tissues. Immunohistochemical analysis showed that a complete and intact intima was the predominant location of MUC18 expression. Although in stenotic arteriosclerotic disease (AP and TEA) the intima was widely calcified, qRT-PCR analysis showed overexpression compared to normal tissue. Interestingly, MUC18 expression was significantly down-regulated in dilatative compared to stenotic arteriosclerotic disease and normal arteries. CONCLUSION: In peripheral stenotic arteriosclerotic disease the proangiogenic potency of MUC18 may play a role in angiogenesis of collaterals, whereas in dilatative aortic diseases the induction of collaterals is typically not evident. The results support the hypothesis of a role in angiogenesis of MUC18 in stenotic arteriosclerotic disease.

Elasticity assessment of electrospun nanofibrous vascular grafts: a comparison with femoral ovine arteries.

Development of successful small-diameter vascular grafts constitutes a real challenge to biomaterial engineering. In most cases these grafts fail in-vivo due to the presence of a mechanical mismatch between the native vessel and the vascular graft. Biomechanical characterization of real native vessels provides significant information for synthetic graft development. Electrospun nanofibrous vascular grafts emerge as a potential tailor made solution to this problem. PLLA-electrospun nanofibrous tubular structures were prepared and selected as model bioresorbable grafts. An experimental setup, using gold standard and high resolution ultrasound techniques, was adapted to characterize in vitro the poly(L-lactic acid) (PLLA) electrospun structures. The grafts were subjected to near physiologic pulsated pressure conditions, following the pressure-diameter loop approach and the criteria stated in the international standard for cardiovascular implants-tubular vascular prostheses. Additionally, ovine femoral arteries were subjected to a similar evaluation. Measurements of pressure and diameter variations allowed the estimation of dynamical compliance (%C, 10(-2) mmHg) and the pressure-strain elastic modulus (E(Pε), 10(6) dyn cm(-2)) of the abovementioned vessels (grafts and arteries). Nanofibrous PLLA showed a decrease in %C (1.38±0.21, 0.93±0.13 and 0.76±0.15) concomitant to an increase in EPε (10.57±0.97, 14.31±1.47 and 17.63±2.61) corresponding to pressure ranges of 50 to 90 mmHg, 80 to 120 mmHg and 100 to 150 mmHg, respectively. Furthermore, femoral arteries exhibited a decrease in %C (8.52±1.15 and 0.79±0.20) and an increase in E(Pε) (1.66±0.30 and 15.76±4.78) corresponding to pressure ranges of 50-90 mmHg (elastin zone) and 100-130 mmHg (collagen zone). Arterial mechanics framework, extensively applied in our previous works, was successfully used to characterize PLLA vascular grafts in vitro, although its application can be directly extended to in vivo experiences, in conscious and chronically instrumented animals. The specific design and construction of the electrospun nanofibrous PLLA vascular grafts assessed in this work, showed similar mechanical properties as the ones observed in femoral arteries, at the collagen pressure range.

Noninvasive imaging of focal atherosclerotic lesions using fluorescence molecular tomography.

Insights into the etiology of stroke and myocardial infarction suggest that rupture of unstable atherosclerotic plaque is the precipitating event. Clinicians lack tools to detect lesion instability early enough to intervene, and are often left to manage patients empirically, or worse, after plaque rupture. Noninvasive imaging of the molecular events signaling prerupture plaque progression has the potential to reduce the morbidity and mortality associated with myocardial infarction and stroke by allowing early intervention. Here, we demonstrate proof-of-principle in vivo molecular imaging of C-type natriuretic peptide receptor in focal atherosclerotic lesions in the femoral arteries of New Zealand white rabbits using a custom built fiber-based, fluorescence molecular tomography (FMT) system. Longitudinal imaging showed changes in the fluorescence signal intensity as the plaque progressed in the air-desiccated vessel compared to the uninjured vessel, which was validated by ex vivo tissue studies. In summary, we demonstrate the potential of FMT for noninvasive detection of molecular events leading to unstable lesions heralding plaque rupture.

Differential endothelial coverage, response to injury and neointimal integration of CX3CR1/smooth muscle-like cells after carotid or femoral arterial injury.

BACKGROUND: Previously, we established the importance of the CX3CL1/CX3CR1 axis in the promotion of myeloid cell differentiation into neointimal smooth muscle-like cells (SMLC). METHODS: In this study, acute (24 h) endothelial coverage and CX3CL1 expression as well as chronic (2 weeks) vascular remodeling was examined with respect to whether myeloid CX3CR1(+) SMLC number in the neointima differed between carotid and femoral artery wire injury. RESULTS AND CONCLUSION: Twenty-four hours after injury, CX3CL1 expression was significantly elevated in injured carotid compared to femoral arteries. In mice with CX3CR1 promoter-driven expression of green fluorescent protein, neointima formation was significantly greater (p < 0.05) 2 weeks after injury in femoral versus carotid arteries as determined by the intima/media ratio. Although the percentage of F4/80/CX3CR1(+) cell integration was similar in both models, the carotid lesion had greater proportions of cells coexpressing CX3CR1 and both α-smooth muscle actin and calponin (p < 0.05). Wire injury of carotid arteries was associated with greater CX3CL1 expression in the acute phase followed by greater CX3CR1 coexpressing SMLC content in later lesions as well as less neointima formation than in femoral arteries. This may, in part, explain the variability in lesion composition after carotid versus femoral wire injury.

[Arterial heterogeneity]. / Artériopathie et hétérogénéité artérielle.

More and more clinical observations and trials support the concept of heterogeneity of atheroma according to the arterial bed. In a pilot study named "Étude Comparative des Lésions Athéromateuses" (ECLA), we have shown that carotid and femoral plaques possess different characteristics. Carotid arteries display increased lipid content compared to femoral arteries whereas femoral arteries are more prone to calcify and to develop osteoid metaplasia. These observations should lead the researcher and the clinician to look at the cellular and molecular mechanisms governing the heterogeneity of atheromas. At last, a better understanding of the characteristics of plaques should help us to determine plaque stability, to prevent cardiovascular events and to choose the best medical, endovascular or surgical option.

Development and characterization of acellular allogeneic arterial matrices.

Surgeons have used cryopreserved vascular allografts successfully for many years to treat arterial occlusive disease and to repair arterial aneurysms. Vascular allografts demonstrate high patency rates but contain viable cells, which may evoke a rejection response following implantation. Removing the cells could prevent such a response and negate the need for cryopreservation and ultra-low temperature storage. The objectives of the study were to characterize human common femoral arteries and develop a decellularization protocol with a view to the generation of biocompatible and biomechanically functional vascular grafts for use in vascular bypass and arteriovenous access. The arteries were decellularized by subjecting the tissue to a single freeze-thaw cycle followed by sequential incubation in hypotonic tris buffer and low concentration sodium dodecyl sulphate. Each artery was disinfected using 0.1% (v/v) peracetic acid. Histological analysis demonstrated a lack of cells following decellularization and confirmed the integrity of the tissue histioarchitecture and retention of major structural proteins. There was a >95% reduction in DNA levels. The acellular tissues and extracts were not cytotoxic to either mouse 3T3 or baby hamster kidney cells. Biomechanical properties were determined by burst pressure, compliance, and tensile tests, which confirmed the retention of biomechanical properties following decellularization. In conclusion the study has developed a suitable protocol for the removal of cells from human common femoral arteries without adversely affecting the biochemical or biomechanical properties. These properties indicate the potential use for acellular human common femoral arteries for vascular bypass or arteriovenous access.