Rabbit Femoral Artery Research Articles

Effects of long-term feeding of α-glucosylhesperidin on the mechanical properties of rabbit femoral arteries

Many people are sensitive to cold, resulting in poor blood circulation. There is evidence that hesperidin results in increased peripheral circulation and skin temperature. A transglycosylated hesperidin, α-glucosylhesperidin, is more bioabsorbable than hesperidin. In the present study, biomechanical studies were performed on the effects of long-term feeding of α-glucosylhesperidin on the contractile response (diameter response) and stiffness of femoral arteries excised from rabbits. Animals in the normal (non-treated), low, and high groups were fed 0, 150 and 4500 mg/day, respectively, of α-glucosylhesperidin for about 24 weeks. The feeding of α-glucosylhesperidin did not change arterial stiffness nor mean blood flow rate in the femoral artery; however, it increased mean aortic blood pressure and decreased arterial diameter at 100 mmHg in the high group. The diameter responses developed by 10-5 M of norepinephrine were significantly lower in the high and low groups than in non-treated group. This result indicates that, due to the long-term feeding of α-glucosylhesperidin, arterial contraction induced by the neurotransmitter of sympathetic nerves decreases. It was estimated that blood flow in such muscular arteries as the femoral artery is maintained at normal by α-glucosylhesperidin even under the conditions of autonomic imbalance and cold intolerance.

Bivalirudin Inhibits Periprocedural Platelet Function and Tissue Factor Expression of Human Smooth Muscle Cells

A major concern of stent implantation after percutaneous coronary intervention (PCI) is acute stent thrombosis. Effective inhibition of periprocedural platelet function in patients with coronary artery disease (CAD) leads to an improved outcome. In this study, we examined the periprocedural platelet reactivity after administrating bivalirudin during PCI compared to unfractionated heparin (UFH) administration. Further, the effect of bivalirudin on induced tissue factor (TF) expression in smooth muscle cells (SMC) was determined. Patients with CAD (n = 58) and double antithrombotic medication were treated intraprocedural with UFH (n = 30) or bivalirudin (n = 28). Platelet activation markers were flow cytometrically measured before and after stenting. The expression of TF in SMC was determined by real-time PCR and Western blotting. The thrombogenicity of platelet-derived microparticles and SMC was assessed via a TF activity assay. Bivalirudin significantly diminished the agonist-induced platelet reactivity post-PCI. Compared to UFH treatment, the adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP)-induced thrombospondin expression post-PCI was reduced when bivalirudin was administrated during intervention. In contrast to UFH, bivalirudin reduced the P-selectin expression of unstimulated and ADP-induced platelets post-PCI. Moreover, bivalirudin inhibited the thrombin-, but not FVIIa- or FVIIa/FX-induced TF expression and pro-coagulant TF activity of SMC. Moreover, bivalirudin reduced the TF activity of platelet-derived microparticles postinduction with TRAP or ADP. Bivalirudin is better than UFH in reducing periprocedural platelet activation. Moreover, thrombin-induced TF expression is inhibited by bivalirudin. Thus, bivalirudin seems to be a better anticoagulant during PCI than UFH.

Anti-Inflammatory Gene Therapy for Cardiovascular Disease

Inflammation in the vascular wall is an essential hallmark during the development of atherosclerosis, for which major leukocytes infiltrated in the lesions are monocytes/macrophages. Therefore, monocyte chemoattractant protein-1 (MCP-1) and its primary receptor CC chemokine receptor 2 (CCR2) are feasible molecular targets for gene therapy to inhibit monocyte/macrophage-mediated inflammation in atherogenesis. A mutant MCP-1 that lacks N-terminal 7 amino acids (7ND) has been shown to heterodimerize with native MCP-1, bind to CCR2 and block MCP-1-mediated monocyte chemotaxis by a dominant-negative manner. Gene therapy using intramuscular transfection with plasmid DNA encoding 7ND showed inhibitory effects on atherosclerosis in hypercholesterolemic mice, and neointima formation after vascular injury in animal models. Bare metal stents for coronary intervention were coated with multiple thin layers of biocompatible polymer with 7ND plasmid. The 7ND gene-eluting stent inhibited macrophage infiltration surrounding stent struts and in-stent neointima formation in rabbit femoral arteries and cynomolgus monkey iliac arteries. Finally, the authors describe new application of 7ND plasmid encapsulated in polymer nanoparticle (NP) that functions as gene delivery system with unique in vivo kinetics. NP-mediated 7ND gene delivery inhibited MCP-1-induced chemotaxis of mouse peritoneal macrophage ex vivo, which may be applicable for the treatment of atherosclerotic cardiovascular disease. In conclusion, anti-inflammatory gene therapy targeting MCP-1/CCR2 signal, with a novel NP-mediated gene delivery system, is a potent therapeutic strategy for the treatment of cardiovascular diseases.

Rho-kinase inhibition attenuates calcium-induced contraction in β-escin but not Triton X-100 permeabilized rabbit femoral artery

K+-depolarization (KCl) of smooth muscle has long been known to cause Ca2+-dependent contraction, but only recently has this G protein-coupled receptor (GPCR)-independent stimulus been associated with rhoA kinase (ROCK)-dependent myosin light chain (MLC) phosphatase inhibition and Ca2+ sensitization. This study examined effects of ROCK inhibition on the concentration-response curves (CRCs) generated in femoral artery by incrementally adding increasing concentrations of KCl to intact tissues, and Ca2+ to tissues permeabilized with Triton X-100, β-escin and α-toxin. For a comparison, tissue responses were assessed also in the presence of protein kinase C (PKC) and MLC kinase inhibition. The ROCK inhibitor H-1152 induced a strong concentration-dependent inhibition of a KCl CRC. A relatively low GF-109203X concentration (1 μM) sufficient to inhibit conventional PKC isotypes also inhibited the KCl CRC but did not affect the maximum tension. ROCK inhibitors had no effect on the Ca2+ CRC induced in Triton X-100 or α-toxin permeabilized tissues, but depressed the maximum contraction induced in β-escin permeabilized tissue. GF-109203X at 1 μM depressed the maximum Ca2+-dependent contraction induced in α-toxin permeabilized tissue and had no effect on the Ca2+ CRC induced in Triton X-100 permeabilized tissue. The MLC kinase inhibitor wortmannin (1 μM) strongly depression the Ca2+ CRCs in tissues permeabilized with Triton X-100, α-toxin and β-escin. H-1152 inhibited contractions induced by a single exposure to a submaximum [Ca2+] (pCa 6) in both rabbit and mouse femoral arteries. These data indicate that β-escin permeabilized muscle preserves GPCR-independent, Ca2+- and ROCK-dependent, Ca2+ sensitization.

Daunorubicin does not induce immunohistochemically detectable endothelial dysfunction in rabbit aorta and femoral artery.

Anthracyclines are one of the most effective anticancer drugs ever developed, but their clinical use has been hampered by the risk of severe cardiotoxicity. In this study, we investigated whether rabbits exposed to a different cumulative dose of anthracycline suffer from immunohistochemically detectable vascular toxicity and endothelial dysfunction. Daunorubicin (3 mg/kg, i.e. 50 mg/m²) was administered i.v. to rabbits once weekly for 1-10 weeks to reach different cumulative doses of the drug (50-500 mg/m²), while control rabbits received saline. The rabbits were sacrificed either 24 hours or 7 days after reaching each particular cumulative dose, and aortas and right femoral arteries were collected for immunohistochemical analysis. Immunohistochemical analysis showed ICAM-1 staining in many aortas from both saline and daunorubicin-treated rabbits without any relationship to the anthracycline treatment. On the contrary, unlike in the lipopolysaccharide-treated or hypercholesterolemic rabbits, no distinct immunoreactivity for other markers of inflammation, oxidative and nitrosative stress (VCAM-1, 4-HNE, iNOS and nitrotyrosine) were detected in aortas and femoral arteries from either control or daunorubicin-treated animals. No relationship to the cumulative dose of the drug or post-expose set up of harvesting was found. In this study, we have demonstrated that daunorubicin does not induce gross histopathological changes in the studied arteries and it fails to induce immunohistochemically detectable endothelial dysfunction. Thus, we propose that endothelial cells are much less susceptible to anthracycline toxicity than cardiac myocytes. In addition, our data suggest that vascular toxicity of anthracyclines plays rather a minor role in the cardiovascular complications of anthracycline chemotherapy.

Role of Na+/K+ ATPase on the relaxation of rabbit ear and femoral arteries.

The role of Na+/K+ ATPase in vascular relaxation has been studied by determining its inhibitory effects on 2-mm segments from rabbit central ear and femoral arteries, mounted for isometric tension recording. Acetylcholine (10(-8)-10(-4) M), the nitric oxide donor sodium nitroprusside (10(-8)-3 x 10(-4) M), the potassium channel agonist cromakalim (10(-8) x 10(-5) M), histamine (10(-8)-10(-4) M) in the presence of the H1 antagonist chlorpheniramine (10(-5) M), and papaverine (10(-6)-3 x 10(-4) M) all produced arterial relaxation in ear and femoral arteries precontracted with endothelin 1. Addition of potassium (6 x 10(-3)-1.2 x 10(-2) M) caused relaxation of the same arteries preincubated in potassium-free medium. Ouabain (10(-5) M) an inhibitor of Na+/K+ ATPase, reduced the relaxation of ear arteries, but not of femoral arteries, in response to acetylcholine; it also reduced the response to sodium nitroprusside, cromakalim or histamine, and abolished the relaxation to potassium, but did not modify the response to papaverine, in both types of artery. These results suggest that Na+/K+ ATPase might play a role in the relaxation of ear and femoral arteries to nitrovasodilators, to potassium channel openers and to activation of histamine receptors, and that Na+/K+ ATPase might play a role in the cholinergic relaxation of ear, but not femoral arteries, suggesting that the mechanism of cholinergic relaxation might differ in each type of artery.

Response of Rabbit Ear and Femoral Arteries to 5-Hydroxytryptamine During Cooling

Abstract The effects of cooling on the response of cutaneous and non-cutaneous arteries to 5-hydroxytryptamine (5-HT) were analysed. Segments 2-mm long from rabbit central ear (cutaneous) and femoral (non-cutaneous) arteries were prepared for isometric tension recording in an organ bath at 37 and 24°C (cooling). 5-HT (10−9-3 times 10−4 M) induced concentration-dependent contraction of the arteries. The sensitivity and maximal contraction of ear arteries and only the maximal contraction of femoral arteries to this amine were reduced at 24°C. Endothelium removal or pretreatment with the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 10−5 m) did not affect the response at 37°C but reversed the decreased sensitivity at 24°C in ear arteries, and neither procedure modified the reactivity at 24 or 37°C in femoral arteries to 5-HT. At both temperatures, the response of ear arteries to 5-HT was shifted to the right by phentolamine (10−6M) more than by the 5-HT antagonist, ketanserin (3 times 10−7M), and that of femoral arteries was shifted to the right by ketanserin or the 5-HT1/5-HT2 antagonist methysergide (3 times 10−7 M) more than by phentolamine, in arteries with and without endothelium. These data concur with the proposition that the contraction to 5-HT is mediated mainly by α-adrenergic receptors in ear arteries and mainly by 5-HT-ergic receptors in femoral arteries, and suggest that cooling reduces the sensitivity of cutaneous, but not of deep arteries to 5-HT, probably by endothelium-nitric oxide-dependent mechanisms.

Development of a total atherosclerotic occlusion with cell-mediated calcium deposits in a rabbit femoral artery using tissue-engineering scaffolds

This study sought to establish a chronic total occlusion (CTO) model with cell-mediated calcium deposits in rabbit femoral arteries. CTO is the most severe case in atherosclerosis and contains calcium deposits. Previous animal models of CTO do not mimic the gradual occlusion of arteries or have calcium in physiological form. In the present study we tested the strategy of placing tissue-engineering scaffolds preloaded with cells in arteries to develop a novel CTO model. Primary human osteoblasts (HOBs) were first cultured in vitro on polycaprolactone (PCL) scaffolds with 5 ng TGFβ1 loading for 28 days for precalcification. The HOB-PCL construct was then implanted into a rabbit femoral artery for an additional 3, 10 or 28 days. At the time of sacrifice, angiograms and gross histology of arteries were captured to examine the occlusion of arteries. Fluorescent staining of calcium and EDS detection of calcium were used to evaluate the presence and distribution of calcium inside arteries. Rabbit femoral arteries were totally occluded over 28 days. Calcium was presented at CTO sites at 3, 10 and 28 days, with the day 10 specimens showing the maximum calcium. Chronic inflammatory response and recanalization were observed in day 28 CTO sites. A novel CTO model with cell-mediated calcium has been successfully established in a rabbit femoral artery. This model can be used to develop new devices and therapies to treat severe atherosclerotic occlusion.

A novel method for the measurement of proximal fibrous cap puncture force in chronic total occlusions: the effect of increasing age

The composition of CTO lesions changes significantly as they age. These changes may adversely affect PCI outcome. We present a robust ex vivo technique to measure the force required to puncture the proximal cap of CTOs, and to determine whether the puncture force differs according occlusion age to examine the effects of compositional changes over time on lesion stiffness. Occlusions were created in 44 rabbit femoral arteries by thrombin injection. Between two and 15 weeks following induction, vessels were harvested and tested in a custom setup to determine the force required to puncture the proximal cap. The puncture force mean values at 2, 6, 12, and 15 weeks were 0.61N, 0.78N, 1.21N and 1.52N, respectively. The puncture force required in occlusions of ≤6 weeks was significantly lower those≥12 weeks (0.72±0.10N versus 1.45±0.13N, p<0.01). Using a cutoff point of 1N, 86% of lesions≤6 weeks of age required<1N compared to 30% of those≥12 weeks. We have shown an objective and reproducible testing system for measuring CTO puncture force. Puncture force is correlated with occlusion age. This technique would be useful to evaluate therapies that alter CTO composition/compliance, as well as guidewire testing.

Active tension adaptation at a shortened arterial muscle length: inhibition by cytochalasin-D

Unlike the static length-tension curve of striated muscle, airway and urinary bladder smooth muscles display a dynamic length-tension curve. Much less is known about the plasticity of the length-tension curve of vascular smooth muscle. The present study demonstrates that there were significant increases of ∼15% in the phasic phase and ∼10% in the tonic phase of a third KCl-induced contraction of a rabbit femoral artery ring relative to the first contraction after a 20% decrease in length from an optimal muscle length (L(0)) to 0.8-fold L(0). Typically, three repeated contractions were necessary for full length adaptation to occur. The tonic phase of a third KCl-induced contraction was increased by ∼50% after the release of tissues from 1.25-fold to 0.75-fold L(o). The mechanism for this phenomenon did not appear to lie in thick filament regulation because there was no increase in myosin light chain (MLC) phosphorylation to support the increase in tension nor was length adaptation abolished when Ca(2+) entry was limited by nifedipine and when Rho kinase (ROCK) was blocked by H-1152. However, length adaptation of both the phasic and tonic phases was abolished when actin polymerization was inhibited through blockade of the plus end of actin by cytochalasin-D. Interestingly, inhibition of actin polymerization when G-actin monomers were sequestered by latrunculin-B increased the phasic phase and had no effect on the tonic phase of contraction during length adaptation. These data suggest that for a given level of cytosolic free Ca(2+), active tension in the femoral artery can be sensitized not only by regulation of MLC phosphatase via ROCK and protein kinase C, as has been reported by others, but also by a nonmyosin regulatory mechanism involving actin polymerization. Dysregulation of this form of active tension modulation may provide insight into alterations of large artery stiffness in hypertension.

Reduction of arterial graft smooth muscle mass by moderate heat therapy

Radial artery (RA) graft spasm is a major cause of early graft failure in coronary artery bypass grafting surgeries. We explored the feasibility of thermal reduction of smooth muscle mass to attenuate vasoconstriction. Rat and rabbit femoral arteries were treated thermally in situ (45°C to 65°C; 0 s to 120 s) and then excised at various time points for histological and physiological study (pressure-diameter relationships). Human radial arteries were treated in vitro and studied in similar fashion. Weeks after thermal treatment, no overt indication was noted of vasospasm, thrombosis, or scarring in the arterial wall; however, this intervention led to a thermal dose-dependent reduction of vasoconstriction (to phenylephrine or potassium chloride) and to a conspicuous loss of smooth muscle. Pressure-diameter relationships showed no aneurismal dilation of these demuscularized arteries up to 200 mmHg. Qualitatively identical results were obtained in human radial arteries. Thermal ablation of RAs may provide a simple, safe, and effective solution to postsurgical vasospasm.

A201 フラボノイドのin vivo投与が家兎大腿動脈の収縮弛緩に及ぼす効果(A2-1 軟組織のバイオメカニクス3)

A201 フラボノイドのin vivo投与が家兎大腿動脈の収縮弛緩に及ぼす効果(A2-1 軟組織のバイオメカニクス3)

E0682 The combined use of urokinase and glycoprotein IIb/IIIa-targeted microbubbles recanalize rabbit femoral artery with thrombotic occlusions

ObjectiveTo determine the effect of the combined use of urokinase and glycoprotein IIb/IIIa-targeted microbubbles prepared by direct conjugation method to dissolve the thromb.MethodsUrokinase and RGDS were in conjunction with microbubbles...

E0695 The combined use of urokinase and glycoprotein IIb/IIIa-targeted microbubbles recanalize rabbit femoral artery with thrombotic occlusions

ObjectiveTo determine the effect of the combined use of urokinase and glycoprotein IIb/IIIa-targeted microbubbles prepared by direct conjugation method to dissolve the thromb.MethodsUrokinase and RGDS were in conjunction with microbubbles...

Intravascular and Extravascular Microvessel Formation in Chronic Total Occlusions: A Micro-CT Imaging Study

The purpose of this study was to characterize the 3-dimensional structure of intravascular and extravascular microvessels during chronic total occlusion (CTO) maturation in a rabbit model. Intravascular microchannels are an important component of a CTO and may predict guidewire crossability. However, temporal changes in the structure and geographic localization of these microvessels are poorly understood. A total of 39 occlusions were created in a rabbit femoral artery thrombin model. Animals were sacrificed at 2, 6, 12, and 24 weeks (n > or =8 occlusions per time point). The arteries were filled with a low viscosity radio-opaque polymer compound (Microfil) at 150 mm Hg pressure. Samples were scanned in a micro-computed tomography system to obtain high-resolution volumetric images. Analysis was performed in an image processing package that allowed for labeling of multiple materials. Two distinct types of microvessels were observed: circumferentially oriented "extravascular" and longitudinally oriented "intravascular" microvessels. Extravascular microvessels were evident along the entire CTO length and maximal at the 2-week time point. There was a gradual and progressive reduction in extravascular microvessels over time, with very minimal microvessels evident beyond 12 weeks. In contrast, intravascular microvessel formation was delayed, with peak vascular volume at 6 weeks, followed by modest reductions at later time points. Intravascular microvessel formation was more prominent in the body compared with that in the proximal and distal ends of the CTO. Sharply angulated connections between the intravascular and extravascular microvessels were present at all time points, but most prominent at 6 weeks. At later time points, the individual intravascular microvessels became finer and more tortuous, although the continuity of these microvessels remained constant beyond 2 weeks. Differences are present in the temporal and geographic patterns of intravascular and extravascular microvessel formation during CTO maturation.

Disturbed blood flow induces erosive injury to smooth muscle cell-rich neointima and promotes thrombus formation in rabbit femoral arteries.

Plaque erosion is a cause of atherothrombosis that preferentially occurs on smooth muscle cell (SMC)- and proteoglycan-rich rather than lipid-rich plaques. However, its underlying mechanisms remain unknown. To determine whether disturbed blood flow induces erosive injury and thrombus formation on SMC-rich neointima. Three weeks after balloon injury, SMC-rich neointima with increased tissue factor (TF) activity developed in rabbit femoral arteries that were narrowed with a vascular occluder to disturb blood flow after stenosis. Neointimal injury and thrombus formation were assessed at 15, 30, and 180 min after the vascular narrowing. Endothelial detachment, platelet adhesion and neointimal cell apoptosis became evident at the post-stenotic regions of all femoral arteries (n = 5) within 15 min of narrowing. Mural thrombi composed of platelet and fibrin developed after 30 min, and then occlusive thrombi were generated in three out of five vessels after 180 min. The identical vascular narrowing of normal femoral arteries also induced endothelial detachment with small platelet thrombi at post-stenotic regions, but fibrin and occlusive thrombi did not develop. Computational simulation analysis indicated that oscillatory shear stress contributes to the development of erosive damage to the neointima. These results suggest that disturbed post-stenotic blood flow can induce erosive injury in SMC-rich plaques and promote thrombus formation that results in vascular events.

Absence of Flow-Mediated Vasodilation in the Rabbit Femoral Artery

The purpose of this study was to determine if there is flow-mediated vasodilation of the femoral artery in response to progressive increases in flow within a physiological range observed in the in vivo experiments. Femoral artery blood flow was determined in conscious rabbits (n = 5) using chronically implanted flowprobes. Resting blood flow was 8.3 +/- 0.6 ml/min and increased to 39.9 +/- 5.4 ml/min during high intensity exercise. Femoral arteries (n = 12, 1705 +/- 43 microm outer diameter) harvested from a separate group of rabbits were mounted on cannulas and diameter was continuously monitored by video system. Functional integrity of the endothelium was tested with acetylcholine. The arteries were set at a transmural pressure of 100 mm Hg and preconstricted with phenylephrine to 73 +/- 3% of initial diameter. Using a roller pump with pressure held constant, the arteries were perfused intraluminally with warmed, oxygenated Krebs' solution (pH = 7.4) over a physiological range of flows up to 35 ml/min. As flow increased from 5 ml/min to 35 ml/min, diameter decreased significantly (p < 0.05) from 1285 +/- 58 microm to 1100 +/- 49 microm. Thus, in vessels with a functional endothelium, increasing intraluminal flow over a physiological range of flows produced constriction, not dilation. Based on these results, it seems unlikely that flow-mediated vasodilation in the rabbit femoral artery contributes to exercise hyperemia.

Modified Approach to Construct a Vascularized Coral Bone in Rabbit Using an Arteriovenous Loop

The most important factor for the survival of thick three-dimensional tissues is the degree of vascularization. In this study, a modified arteriovenous loop (AVL) model was developed to prefabricate an axial vascularized tissue-engineered coral bone. In group A (n = 28), an arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. The AVL was placed in a coral block (6 x 8 x 10 mm (3)) as a vascular carrier. The complex was wrapped with polytetrafluoroethylene membrane and implanted subcutaneously. In group B (n = 20), there was no vascular carrier, and the same dimensional coral was directly implanted beneath inguinal skin. After 2, 4, 6, and 8 weeks, the rabbits were perfused with heparinized saline (for scanning electron microscopy), India ink (for histological examination), and ethylene perchloride (for vascular casts) via the abdominal aorta. In group A, histology showed that newly formed vasculature extended over the surfaces and invaded the entire coral blocks. The vascular density was significantly superior to that in group B. Vascular casts showed that new blood vessels robustly sprouted from the AVL. Scanning electron microscopy demonstrated that there were minute sprouting cavities in the vascular endangium. In this model, an axial vascularized coral bone could be effectively constructed.

Pharmacological Studies on Responsiveness of 5-Hydroxytryptamine to Overcome Perioperative Spasm of Coronary Artery Bypass Graft

In ischemic heart diseases, the use of the internal thoracic artery (ITA) as an arterial graft has been associated with longer survival and better quality of life. However, it has been reported that vasospasm of the ITA graft frequently occurs and increases perioperative and postoperative morbidity. Serotonin (5-HT) plays an important role in the occurrence of vasospasm. We examined 5-HT receptor subtypes responsible for the 5-HT-induced vasocontraction in the human ITA. The contractile response caused by 5-HT was mediated by activation of not only 5-HT(2A) receptors but also 5-HT(1B) receptors. We also examined the relationship between 5-HT-induced vasocontraction of the rabbit femoral artery and arteriosclerosis using the arteriosclerosis model of repeated balloon-injury. The contractile response caused by 5-HT in the femoral artery with arteriosclerosis was significantly greater than that in the normal artery. Additionally, we demonstrated that insulin induced internalization of 5-HT(2A) receptors from the plasma membrane in HEK293 cells. Diabetes mellitus (DM) is a risk factor for ischemic heart diseases. We evaluated the 5-HT-induced vasocontraction, mediated by activation of 5-HT(2A) and 5-HT(1B) receptors, in the ITA obtained from patients with DM or without DM undergoing coronary bypass surgery. The contractile response caused by 5-HT in the ITA from patients with DM was significantly greater than that from patients without DM. Our findings suggest that when the ITA is used as an arterial graft, simultaneous treatment with 5-HT(2A) and 5-HT(1B) receptor antagonists is useful to prevent 5-HT-induced vasospasm, especially in patients with DM.

Ultrasound-targeted microbubbles mediated VEGF gene delivery to injured artery in vivo

Objective To comparatively investigate the VEGF gene transfer of rabbit femoral artery balloon-injured models mediated by targeted-ultrasound or microbubble. Methods The plasmid pCDNA3.1 (-)/hVEGF165 was constructed. The rabbit models of injured femoral artery were established, and randomly divided into 5 groups: Group 1, the control; Group 2, blank plasmid + ultrasound + microbubbles; Group 3, VEGF plasmid; Group 4, VEGF plasmid + microbubbles; Group 5, targeted-ultrasound (VEGF plasmid + ultrasound + microbubbles). After two weeks from operation, the VEGF staining degree was observed from harvested injured artery segment by immunohistochemistry. Furthermore,RT-PCR and western blot analysis were performed to evaluate the expression level of VEGF. Results A lot of brown-yellow VEGF positive particles were visible in group 4 and group 5 by immunohistochemistry. RT-PCR and Western Blot analysis showed VEGF expression was significantly increased in group 5 than the other four groups(P 0.05). Conclusions Above these observations,it is believed that both microbubble and targeted-ultrasound can facilitate VEGF gene transfer of vascular endothelial. Targeted-ultrasound group transfer efficiency is higher than that of microbubble group, and the plasmid alone can not promote transfer of vascular endothelial. Key words: Ultrasonography; Microbubbles; Transfection; Femoral artery