Femoral Artery Model Research Articles

Obesity promotes injury induced femoral artery thrombosis in mice

An FeCl 3 induced femoral arterial thrombosis model was applied to lean (47 ± 1.4 g) and obese (64 ± 1.7 g) mice (Swiss genetic background) in order to study the relation between obesity and thrombotic risk. As compared to lean mice, obese mice showed a significantly shorter occlusion time (9.9 ± 1.0 min versus 13 ± 0.5 min; p = 0.04) and lower total blood flow (37 ± 7.3% versus 69 ± 6.7%; p = 0.008). A significant negative correlation was observed between body weight and both occlusion time ( r = − 0.57; p = 0.014) and blood flow ( r = − 0.57; p = 0.028). Analysis of the coagulation profile revealed significantly higher levels of plasminogen activator inhibitor-1 (PAI-1), thrombin–antithrombin complex, Factor V activity and combined Factors II/VII/X activity, and moderately elevated Factor VIII activity in obese mice. The degree of arterial damage and the thrombus extension were, however, not significantly different. A significant positive correlation was observed between body weight and either PAI-1 ( r = 0.63; p = 0.003), Factors II/VII/X levels ( r = 0.80; p < 0.0001) or Factor V levels ( r = 0.65; p = 0.003). Thus, this injury induced femoral artery thrombosis model in mice establishes experimentally a correlation between obesity and prothrombotic tendency.

Numerical simulation of in vitro pulsatile flow and its study using FRISK, a rapid phase contrast technique

To test the potential of a phase contrast magnetic resonance (PC-MR) sparse sampling technique, fragmented regional interpolation segmentation for k-space (FRISK), to capture complex flow features within a breathhold duration by using numerical simulations and experimental approaches. Computational fluid dynamics (CFD) data of three models were generated: a two-chamber orifice flow model simulating valvular regurgitation, a femoral artery model, and a U-shaped model simulating the aortic arch. These data were used to simulate conventional and FRISK PC-MR data acquisitions. FRISK parameters can be adapted for different flow fields to capture either high temporal information or complexly varying spatial information with a temporal component or a mixture of both. In vivo PC-MR images on a healthy volunteer were sampled to compare conventional PC-MR with novel FRISK imaging. In our simulations of three representative models, when only the errors from different sampling sequences were considered, FRISK was shown to maintain or even improve data accuracy while cutting the scan time by at least 50% compared to corresponding conventional PC-MR. By adapting the FRISK parameters for flowfields with different features, FRISK was capable of capturing in-plane and through-plane velocity information with excellent detail in approximately 20 heartbeats breathhold duration. The results of the in vivo MR experiment were consistent with the simulation results, showing that breathhold FRISK imaging improved spatial resolution of the data and maintained adequate temporal resolution compared with breathhold conventional imaging. FRISK, a new MRI sampling sequence that sparsely samples data and aligns acquired data during postprocessing, provides a scan time advantage of approximately a factor of 2 compared to conventional scans, and allowed rapid or breathhold scanning while obtaining acceptable accuracy.

THE ADENOSINE 2A RECEPTOR AGONIST ATL-146E ATTENUATES EXPERIMENTAL POSTHEMORRHAGIC VASOSPASM

Selective adenosine 2A receptor agonists, such as ATL-146e, are known to be potent anti-inflammatory agents devoid of systemic side effects and have been used clinically in a number of disease states. However, adenosine 2A receptor agonists have not been studied in the treatment of cerebral vasospasm after subarachnoid hemorrhage. The present study investigated the efficacy of ATL-146e in the prevention of leukocyte infiltration and attenuation of posthemorrhagic vasospasm. The rodent femoral artery model of vasospasm was used. Forty male Sprague-Dawley rats were randomly assigned to four different groups (vehicle, 1 ng/kg/min, 10 ng/kg/min, or 100 ng/kg/min ATL-146e administered via subcutaneous osmotic minipump). Vasospasm was evaluated at posthemorrhage Day 8 (period of peak constriction) by calculating the lumen cross-sectional area (expressed as percent change in luminal area: ratio of blood-exposed vessel to normal saline-exposed vessel) and radial wall thickness. Immunostaining with anti-CD45 monoclonal antibody to detect leukocytes was used to evaluate localized inflammation. Significant vasospasm was noted in the vehicle-treated (blood-exposed) control group (78.5%, P < 0.001; expressed as a ratio of luminal area of the saline [no blood] control), but not in the ATL-146e-treated groups (lumen ratio to control: 105.0, 83.4, and 91.3% for the 1, 10, and 100 ng/kg/min groups, respectively). Additionally, infiltration of inflammatory cells was reduced significantly and radial wall thickness was decreased in the ATL-146e-treated groups compared with the vehicle-treated control group. Selective activation of the adenosine 2A receptor with ATL-146e prevented posthemorrhagic vasospasm and reduced leukocyte infiltration in this experimental model. This agent is worthy of further investigation and lends credence to the hypothesis supporting a role for inflammation in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage.

Chitosan Dressing Provides Hemostasis in Swine Femoral Arterial Injury Model

Objective. Chitosan dressings have been shown to be effective in improving survival of severe parenchymal injuries in an animal model andin treating prehospital combat casualties. Our goal was to test the efficacy of chitosan acetate dressings in providing durable hemostasis in a high-flow arterial wound model. Methods. A proximal arterial injury was created with 2.7-mm vascular punches in both femoral arteries of fourteen anesthetized swine. By using a crossover design, 48-ply gauze (48PG) or a chitosan dressing (HC) was applied with pressure to the injury for 3 minutes andthen released. If hemostasis was not maintained for 30 minutes, a second identical attempt was made by using the same dressing type. If hemostasis was still not achieved, the dressing was considered an acute failure andthe alternate dressing type was applied. If failure of hemostasis occurred between 30 and240 minutes after application, the dressing was considered a chronic failure andthe artery was ligated. Results. All 25/25 (100%) of the HC tests and3/14 (21%) of the 48PG maintained hemostasis for 30 minutes. At 240 minutes, 21/25 (84%) of the HC tests and1/14 (7%) of the 48PG maintained hemostasis. Statistical analysis by Fischer's exact test shows a significant (p < 0.001) difference in hemostatic efficacy between the 48PG andHC groups in this model, both at 30 minutes andat 240 minutes. Conclusion. Chitosan acetate hemorrhage control dressings provided superior hemostasis to 48 ply gauze in high inguinal femoral arterial injuries. Chitosan-based dressings may provide prehospital treatment options for hemostasis in patients with severe hemorrhagic arterial injuries.

A New Technique For Microvascular Anastomosis

In our experimental study of a new microvascular anastomosis technique, we divided 30 Wistar albino rats into 2 groups. We performed the classic interrupted suture anastomosis technique in group 1 (n = 15) and our new technique, using 3 horizontal mattress sutures, in group 2 (n = 15). We checked patency immediately following anastomosis, at the end of the first hour, and at the end of the third week postanastomosis. While the patency rates for both techniques were 100% at the end of the first hour, the respective values were 100% and 93.4% by the end of the third week. Using light microscopy, lumen patency, intimal and medial damage, inflammation, and granulation were evaluated histopathologically. The mean anastomosis time for the experimental group (15 minutes) was shorter than that for the classic group (mean 21 minutes), and the difference was statistically significant (P < 0.01), while the difference between the patency rates was not significant (P = 0.05). Therefore, provided that the incisions are made correctly, our microvascular anastomosis technique using 3 horizontal mattress sutures can be used in experimental and clinical studies.

A Novel Inhibitor Of Inflammatory Cytokine Production (CNI-1493) Reduces Rodent Post-Hemorrhagic Vasospasm

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is a devastating complication, yet despite multiple lines of investigation an effective treatment remains lacking. Cytokine-mediated inflammation has been implicated as a causative factor in the development of posthemorrhagic vasospasm. In previous experiments using the rat femoral artery model of vasospasm, we demonstrated that elevated levels of the proinflammatory cytokine interleukin (IL)-6 are present after hemorrhage and that a polyclonal antibody against IL-6 is capable of attenuating experimental vasospasm. In the present study, we tested the ability of a novel selective proinflammatory cytokine inhibitor (CNI-1493) to protect against the occurrence of experimental vasospasm in the same rat femoral artery model. CNI-1493 was administered by injection directly into the blood-filled femoral pouches of animals at the time of their initial surgery (hemorrhage). Control animals received an equal volume of vehicle alone. Animals were killed at 8 days posthemorrhage and degree of vasospasm was assessed by image analysis of artery cross-sectional area. In a separate series of experiments, enzyme-linked immunosorbent assay (ELISA) was used to assess levels of the proinflammatory cytokine IL-6 and the prototypical antiinflammatory cytokine transforming growth factor (TGF)-beta1 after treatment with CNI-1493. Pretreatment with CNI-1493 provided dose-dependent attenuation of posthemorrhagic vasospasm, with the highest dose (200 microg in 8 microL dH2O) causing complete reversal of vasospasm (vessel cross-sectional area ratio 1.06 +/- 0.04 versus 0.87 +/- 0.06, p < 0.05, one-way analysis of variance). Assessment of cytokine levels by ELISA confirmed the selectivity of CNI-1493 by demonstrating significant reductions in IL-6 levels, but no suppression of TGF-beta1 levels. These findings support the conclusion that inflammatory cytokines, in particular IL-6, play an important role in development of vasospasm in the rat femoral artery model. Furthermore, these results suggest that the inhibition of inflammatory cytokines may be an appropriate strategy for the treatment of vasospasm after SAH.

Learning to Perform Microvascular Anastomosis

The skills necessary to connect ultrasmall vessels and neural structures successfully require commitment and practice to refine. The techniques require only a few specialized instruments and a high-quality microscope. Several exercises can simulate real-life anatomical situations using a rubber sheet, chicken vessels, or the rat femoral artery model. A series of graduated drills can help develop proficiency and confidence.

Vascular Remodeling in Mice Lacking the Cytoplasmic Domain of Tissue Factor

Tissue factor (TF), the cell surface receptor for the serine protease FVIIa supports cell migration by interaction with the cytoskeleton. Intracellular signaling pathways dependent on the cytoplasmic domain of TF modify cell migration and may alter vascular remodeling. Vascular remodeling was analyzed in a femoral artery injury and a blood flow cessation model in mice with a targeted deletion of the 18 carboxy-terminal intracellular amino acids of TF (TF(Deltact/Deltact)) and compared with TF wild-type mice (TF(wt/wt)). Morphometric analysis revealed a decrease in the intima/media ratio after vascular injury in arteries from TF(Deltact/Deltact) compared with TF(wt/wt) mice (femoral artery injury: 2.4+/-0.3 TF(wt/wt) versus 0.6+/-0.3 TF(Deltact/Deltact), n=9 to 10, P=0.002; carotis ligation: 0.45+0.11 TF(wt/wt) versus 0.22+0.03 TF(Deltact/Deltact), n=12 to 14, P=0.09). This was caused by an increase in the media by 54% (P=0.04) in the femoral artery model and by 32% (P=0.03) after carotis ligation and was associated with an increased number of proliferating cells. Isolated aortic smooth muscle cells (SMCs) of TF(wt/wt) mice showed an increased migratory response toward the TF ligand active site-inhibited FVIIa that was abolished in TF(Deltact/Deltact) SMC. In contrast, the unstimulated proliferation rate was increased in TF(Deltact/Deltact) SMC compared with TF(wt/wt) SMCs. Thus, retention of SMCs attributable to a migratory defect and increased proliferation results in thickening of the media and in decrease in neointima formation after arterial injury. TF cytoplasmic domain signaling alters vascular remodeling and, thereby, may play a role in the development of restenosis, atherosclerotic disease, and neovascularization.

Macrophage depletion reduces monocyte chemotactic protein-1 and transforming growth factor-β 1 in healing rat vein grafts

Objective We previously showed that treatment with liposomally encapsulated dichloromethylene bisphosphonate reduces intimal hyperplasia development and macrophage accumulation in a rat epigastric vein to femoral artery model of intimal hyperplasia. Our objective in this study was to determine the effect of liposomally encapsulated dichloromethylene bisphosphonate on the expression of two cytokines essential to neointimal development, monocyte chemotactic protein-1 (MCP-1) and transforming growth factor-β 1 (TGF-β). Methods We injected rats both 2 days preoperatively and 2 weeks postoperatively with liposomally encapsulated dichloromethylene bisphosphonate (Lip-Clod), liposomally encapsulated phosphate-buffered saline solution (Vector), or phosphate-buffered saline solution (PBS), and harvested the grafts at 1 and 4 weeks. In the perianastomotic region, MCP-1 and TGF-β protein expression in the total graft cross-section and in the neointima was determined with immunohistochemistry. In whole-graft lysates, MCP-1 and TGF-β protein were determined with an enzyme-linked immunosorbent assay, and messenger RNA expression was determined with reverse transcription quantitative polymerase chain reaction. Results Lip-Clod treatment reduced intimal hyperplasia when compared with Vector or PBS treatment. These reductions were significant ( P < .05) at both time points. When compared with the PBS treatment, at 1 week but not at 4 weeks Lip-Clod reduced both MCP-1 and TGF-β protein ( P ≤ .01 and P ≤ .006) in the perianastomotic region of vein grafts. In whole-graft lysates, no significant difference was seen in MCP-1 protein at either time point; however, TGF-β protein expression was significantly reduced at both 1 and 4 weeks ( P = .02 and P = .004). Message analysis in whole-graft lysates at 1 week showed that MCP-1 message expression increased in the Lip-Clod group compared with the PBS group ( P = .02), but no significant differences among groups for TGF-β message levels. Results with Vector were often intermediate to results with Lip-Clod and PBS. Conclusion The major effect of Lip-Clod treatment on TGF-β and MCP-1 protein levels in the perianastomotic region is observed at 1 week, and macrophage depletion with Lip-Clod inhibits graft neointimal hyperplasia and TGF-β protein expression in whole-graft lysates at 1 and 4 weeks. These results support the concept that the infiltrating macrophages contribute a significant portion of the cytokines that facilitate intimal hyperplasia and that reducing these cytokines early after grafting influences the development of intimal hyperplasia at later time points. Clinical relevance All vascular surgeons have patients who have undergone a technically satisfying vein graft, only to have the bypass fail during the first year due to perianastomotic intimal hyperplasia (IH). We hypothesize that vein graft IH is analogous to aberrant wound healing. Central to wound healing is the recruitment of macrophages with their cytokines. This work raises the question whether clinical strategies designed to either decrease macrophages or the cytokines released by macrophages at the time of vein graft placement will be efficacious for limiting the development of IH.

Neutralizing Antibody against Interleukin-6 Attenuates Posthemorrhagic Vasospasm in the Rat Femoral Artery Model

The degree to which inflammation contributes to the development of posthemorrhagic vasospasm is controversial. In the present study, we investigated the relationship between various inflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-1alpha, IL-1beta, and IL-6) and the development of experimental vasospasm. Posthemorrhagic vasospasm was produced in the rat femoral artery model. A latex pouch was placed around each femoral artery, and one pouch was injected with autologous blood and the other with saline as an internal control. Animals were killed at various time points (1 h to 16 d) after surgery (blood exposure), and the degree of vasospasm was assessed by image analysis of artery cross sectional area. Levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay, and the ability of a polyclonal antibody against rat IL-6 to inhibit vasospasm was tested. The rat femoral artery model produced a biphasic vasospasm response, with maximal chronic delayed vasospasm occurring at 8 days after hemorrhage. Enzyme-linked immunosorbent assay revealed a significant increase in IL-6 concentrations in blood-exposed arteries relative to saline-exposed arteries at multiple time points (6, 12, 24, and 48 h) after hemorrhage (P < 0.0001). A relative increase in IL-1alpha levels was noted at 24 hours (P < 0.01). IL-1beta levels were similarly elevated in both blood- and saline-exposed arteries, and tumor necrosis factor-alpha levels were not detectable. Administration of a neutralizing polyclonal antibody against rat IL-6 directly into the blood-exposed periarterial pouch at the time of initial surgery resulted in a dose-dependent reduction in the degree of vasospasm compared with vehicle-treated controls at 8 days after hemorrhage (P < 0.05). These results indicate that cytokine-mediated inflammation is active in the setting of posthemorrhagic vasospasm produced by the rat femoral artery model. In particular, the profound increase in IL-6 levels after exposure to hemorrhage and the ability of a polyclonal antibody against IL-6 to reduce vasospasm suggest that IL-6 may play a prominent role in the development of vasospasm in this model.

Inhibition of restenosis by tissue factor pathway inhibitor: in vivo and in vitro evidence for suppressed monocyte chemoattraction and reduced gelatinolytic activity

AbstractActivation of inflammatory and procoagulant mechanisms is thought to contribute significantly to the initiation of restenosis, a common complication after balloon angioplasty of obstructed arteries. During this process, expression of tissue factor (TF) represents one of the major physiologic triggers of coagulation that results in thrombus formation and the generation of additional signals leading to vascular smooth muscle cell (VSMC) proliferation and migration. In this study, we have investigated the mechanisms by which inhibition of coagulation at an early stage through overexpression of tissue factor pathway inhibitor (TFPI), an endogenous inhibitor of TF, might reduce restenosis. In a rabbit femoral artery model, percutaneous delivery of TFPI using a recombinant adenoviral vector resulted in a significant reduction of the intimamedia ratio 21 days after injury. Investigating several markers of inflammation and coagulation, we found reduced neointimal expression of monocyte chemoattractant protein-1 (MCP-1), lesional monocyte infiltration, and expression of vascular TF, matrix metalloproteinase-2 (MMP-2), and MMP-9. Moreover, overexpression of TFPI suppressed the autocrine release of platelet-derived growth factor BB (PDGF-BB), MCP-1, and MMP-2 in response to factors VIIa and Xa from VSMCs in vitro and inhibited monocyte TF activity. These results suggest that TFPI exerts its action in vivo through not only thrombotic, but also nonthrombotic mechanisms.

Collagenase Plaque Digestion for Facilitating Guide Wire Crossing in Chronic Total Occlusions

Chronic total occlusions (CTOs) are associated with significant angina, impaired left ventricular function, and worse long-term outcomes. Percutaneous coronary interventions in CTO are unsuccessful in up to 50% of cases, primarily because of inability to cross the lesion with a guide wire. Collagen is the predominant component of the atherosclerotic plaque. The objective of this study was to determine the efficacy and toxicity of local delivery of a collagen-degrading enzyme to facilitate guide wire crossing in CTO. Type IA collagenase (100 or 450 microg) or placebo was locally administered to 45 CTOs in a rabbit femoral artery model. Mean occlusion duration was 16+/-5 weeks. Attempts to cross the CTO (mean length, 28+/-9 mm) with conventional guide wires were assessed at 72 hours after treatment. An additional 3 arteries per group were assessed for collagenase effects at 24 hours after treatment. Successful guide wire crossings were significantly higher in collagenase-treated arteries (13 of 21, 62%) than in placebo-treated arteries (7 of 24, 29%) (P=0.028). No adverse effects on arterial structure were observed in collagenase-treated arteries. At 24 hours, collagenase-treated arteries demonstrated increased collagenase protein, gelatinase activity, and collagen fragments. Local delivery of collagenase can safely facilitate guide wire crossing of CTO. This novel approach could lead to higher percutaneous coronary intervention success rates in CTO.

Inhibition of vasospasm with lymphocyte function-associated antigen-1 monoclonal antibody in a femoral artery model in rats.

The authors have previously shown that a monoclonal antibody (mAb) that recognizes intercellular adhesion molecule-1 (ICAM-1), also known as CD54, when administered systemically inhibits experimental vasospasm in a rat femoral artery model, suggesting that ICAM-1 and leukocyte-endothelial adhesion play a crucial role in the molecular chain of events leading to posthemorrhagic vasospasm. In this report the authors confirm this hypothesis with mAbs directed against lymphocyte function-associated antigen-1 ([LFA-1] CD11a/CD18), the molecule on the surface of leukocytes that interacts with ICAM-1. Femoral arteries in 38 Sprague-Dawley rats were isolated and exposed to autologous blood. Twenty-nine animals were then randomized into three groups and received intraperitoneal injections of anti-LFA-1 mAb (10 rats), anti-ICAM-1 mAb (10 rats), or an isotype-matched control mAb (nine rats). Injections were administered at 3 hours and 3, 6, and 9 days after surgery. Before their deaths, six animals underwent spleen harvest, and splenocytes were used in fluorescence-activated cell sorter (FACS) analysis to verify saturation of appropriate binding sites. Animals were killed at 12 days and vessels were harvested for histological study and measurement of the luminal cross-sectional area. Nine animals were randomized as earlier, killed 24 hours after a single injection of mAb, and evaluated for periadventitial infiltration of granulocytes and macrophages. Results of FACS analysis demonstrated saturation of both LFA-1 and ICAM-1 binding sites in animals treated with the respective mAb. The mean ratios of blood-exposed to saline-exposed luminal cross-sectional areas (expressed as the percentage of lumen patency) were 90.1 +/- 5.8% (mean +/- standard error of the mean) for animals treated with the anti-LFA-1 mAb (p = 0.0218), 94.2 +/- 3.3% for animals treated with the anti-ICAM-1 mAb (p = 0.0067), and 62 +/- 7.4% for animals treated with the isotype-matched control mAb. Macrophage and granulocyte counts in the periadventitial region were 39.5 +/- 3.2/hpf for animals treated with anti-LFA-1 mAb (p = 0.001), 42 +/- 3.7/hpf for animals treated with anti-ICAM-1 mAb (p = 0.003), and 72.2 +/- 6.2/hpf for control animals. The systemic administration of anti-LFA-1 or anti-ICAM-1 mAb initiated 3 hours after exposure to autologous blood inhibits the development of delayed chronic vasospasm at 12 days in a rat femoral artery model and leads to a significant reduction in periadventitial inflammatory cells at 24 hours. The authors conclude that blocking the migration of inflammatory cells across the endothelial surface of an artery after adventitial exposure to blood prevents the initiation of biological cascades necessary for the subsequent development of chronic vasospasm.

Endothelial cell seeding of a 4-mm I.D. polyurethane vascular graft.

We evaluated the extent (luminal coverage) of the endothelial cell (EC) lining/neointimal development and the thromboresistance of electrostatically EC seeded small diameter ChronoFlex-polyurethane vascular grafts. The evaluation consisted of harvesting autologous, canine jugular vein ECs, electrostatically seeding the polyurethane grafts (4-mm I.D., length = 6 cm) with the harvested ECs, implanting the grafts in a canine femoral artery model for four to six weeks, and excising the grafts for histological and scanning electron microscopy evaluations. Results of the histological evaluation (mid-graft region only) indicated that electrostatic EC seeding led to neointimal development and to minimal to no thrombus formation within the EC seeded grafts. The unseeded control grafts resulted in no neointimal development and substantial thrombus formation on the graft luminal surfaces. Scanning electron microscopy examination demonstrated a mature, confluent endothelium with a "cobblestone" appearance on the EC seeded graft luminal surface after six weeks. We conclude that electrostatic EC seeding enhanced the development of a neointima and reduced the incidence of thrombosis in polyurethane grafts implanted in a canine femoral artery model.

Mouse genetic evidence that tranilast reduces smooth muscle cell hyperplasia via a p21(WAF1)-dependent pathway.

N-(3'4'-dimethoxycinnamoyl)-anthranilic acid (tranilast) is a drug that has been shown to reduce the incidence of restenosis after angioplasty in middle-scale clinical trials. Despite clinical interest in this drug, the pharmacological actions of tranilast remain relatively unexplored at a molecular level. We evaluated the effects of tranilast on vascular smooth muscle cell (VSMC) proliferation in wild-type mice and in mice lacking a cyclin-dependent kinase inhibitor, p21(WAF1) (p21). Tranilast potently inhibited the proliferation of VSMC cultures derived from wild-type mice, but VSMCs derived from p21-deficient (p21-/-) mice were unaffected by this treatment. In a mouse femoral artery model of vascular injury, tranilast administration to wild-type mice led to an upregulation of p21 expression and a decrease in the number of proliferating VSMCs, as determined by immunostaining for proliferating cell nuclear antigen. In contrast, tranilast had no effect on the number of proliferating cell nuclear antigen-positive cells in the injured arteries of p21-/- mice. Administration of tranilast significantly reduced the neointimal VSMC hyperplasia in wild-type mice at 4 weeks but had no effect on lesion formation in p21-/- mice. Our findings provide genetic evidence that tranilast inhibits intimal hyperplasia via a p21-dependent pathway, an activity that may contribute to its efficacy in the prophylactic treatment of postangioplasty restenosis.

The persistence of electrostatically seeded endothelial cells lining a small diameter expanded polytetrafluoroethylene vascular graft.

The purpose of this study was to evaluate the persistence of electrostatically seeded endothelial cells (ECs) lining an expanded polytetrafluorethylene (e-PTFE) graft after one week exposure to in vivo circulation in a canine femoral artery bypass model. This was accomplished by visualizing the PKH 26 (red fluorescent) label placed in the EC membranes prior to the seeding procedure. Furthermore, this study was performed to confirm that the source of the ECs lining the graft were those from the initial inoculum. This evaluation consisted of harvesting autologous, canine jugular vein ECs, PKH 26 labeling of the ECs, electrostatic EC seeding the e-PTFE grafts (4mm GORE-TEX, Length=6cm), implanting the grafts (femoral artery model) for one week, and explanting the grafts for light, fluorescent and scanning electron microscopy evaluations of the luminal surface. The unseeded grafts (controls) had a mean fluorescence surface coverage of 6.82 +/- 7.19%, while the EC seeded grafts had a mean of 90.3 +/- 14.3% which is significantly (p <0.001) different from the controls. Overall, the seeding time including the EC harvesting and PKH 26 labeling protocol was approximately 75 min. The electrostatically seeded ECs persisted after implantation of the graft as demonstrated by the PKH 26 labeling data. The fluorescent data also demonstrated that the neointima formed (EC luminal surface coverage) one week after implantation was in fact derived from the ECs initially seeded as determined by the abundance of the labeled ECs.

Inhibition of experimental vasospasm by pretreatment with ultraviolet light irradiation in a rat femoral artery model.

Chronic cerebral vasospasm is resistant to conventional treatments despite recent advances in treatment modalities. We studied the preventive effect of ultraviolet (UV) irradiation on development of vasospasm and its mechanism in a rat femoral artery model. The rat femoral artery model for vasospasm was used in this investigation (n = 108). The femoral arteries were divided into four groups: empty and no irradiation (control), UV irradiation (UV group), blood placement (VS group), and blood placement after UV irradiation (VS + UV group). Luminal area was measured, and smooth muscle cell counts in the medial layer of the vessel wall were obtained. An immunohistochemical study was performed with cross sections of fixed femoral arteries at 12 hours and 1, 3, 5, 7, and 49 days after blood placement. The rings of femoral arteries on Day 7 were subjected to pharmacological study. Pretreatment with UV irradiation (VS + UV group) resulted not only in significant inhibition of chronic vasospasm but also in a significant decrease in smooth muscle cells compared with the VS group on Days 5 and 7. The UV-treated arteries (UV and VS + UV groups) exhibited a significant number of Bax- and Bcl-2-positive cells on Days 5 and 7, but few CPP-32 positive cells were observed at the same time points. In the pharmacological study, contractile response to KCI or phenylephrine was reduced significantly in the UV-treated arteries. These results imply that UV irradiation prevents chronic vasospasm and suggest that UV-induced cell death plays an important role in the preventive effect without causing complications during the chronic period.

Inhibition of Experimental Vasospasm by Pretreatment with Ultraviolet Light Irradiation in a Rat Femoral Artery Model

Inhibition of Experimental Vasospasm by Pretreatment with Ultraviolet Light Irradiation in a Rat Femoral Artery Model

Inhibition of Experimental Vasospasm by Pretreatment with Ultraviolet Light Irradiation in a Rat Femoral Artery Model

Inhibition of Experimental Vasospasm by Pretreatment with Ultraviolet Light Irradiation in a Rat Femoral Artery Model

Rebamipide prevents periarterial blood-induced vasospasm in the rat femoral artery model

We examined the effect of rebamipide on the vasospasm induced by periarterial blood. In the in vitro study, the significant production of superoxide anion that was identified 3 hours after application of 10% whole blood to the rat aortic segments was inhibited by rebamipide (100 and 300 μ M) and these results were correlated with the in vitro intercellular adhesion molecule-1 (ICAM-1) expression on the femoral artery. In thein vivo study, there was an increased mobilization of granulocytes in parallel with a large expression of ICAM-1 in the vessels 24 hours after periarterial blood was applied to the femoral artery which then declined. Subsequently, infiltration of macrophages progressively increased at all layers 7–12 days after application. Pretreatment with rebamipide (100 and 300 mg kg−1day−1, p.o.) significantly inhibited the morphological changes as well as the expression of ICAM-1 with inhibition of granulocyte/macrophage mobilization. In association with these findings, increased wall thickness and decreased lumen area were significantly inhibited by pretreatment with rebamipide. These results provide valuable information for the therapeutic use of rebamipide to relieve vascular remodeling induced by periarterial blood.