Femoral Vein Ligation Research Articles

Experience of vascular injuries at a military hospital in Korea.

Vascular injuries require immediate surgical treatment with standard vascular techniques. We aimed to identify pitfalls in vascular surgery for trauma team optimization and to suggest recommendations for trauma and vascular surgeons. We reviewed 28 victims and analyzed the patterns of injuries, methods of repair, and outcomes. Ten patients had torso injuries, among whom three thoracic aorta injuries were repaired with thoracic endovascular aortic repair, one left hepatic artery pseudoaneurysm with embolization, and two inferior vena cava with venorrhaphy, three iliac arteries with patch angioplasty or embolization, and three common femoral arteries with bypass surgery or arterioplasty. Four patients had upper extremity injuries, among whom one brachial artery and vein was repaired with bypass surgery after temporary intravascular shunt perfusion, two radial arteries were repaired with anastomoses, and one ulnar artery was repaired with ligation. One radial artery under tension was occluded. Fourteen patients had lower extremity injuries, among whom one superficial femoral artery and vein was repaired with bypass and concomitant ligation of the deep femoral artery and vein, three superficial femoral arteries were repaired with bypass (two concomitant femoral veins with bypass or anastomosis), one deep femoral artery with embolization, two popliteal arteries with bypass or anastomosis, four infrapopliteal transected arteries, one arteriovenous fistula with ligation, and one pseudoaneurysm with bypass. However, one superficial femoral artery and all femoral veins were occluded. One leg replantation failed. There are potential complications of vascular access during resuscitative endovascular balloon occlusion of the aorta procedures. Vascular repair should be performed without tension or spasm. Preservation of the harvested vein in papaverine solution and blood while using a temporary intravascular shunt is a method of eliminating spasms.

Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors.

This study aimed to evaluate the effects of delayed femoral vein ligation on the clinical outcomes of hip disarticulation. We retrospectively reviewed 20 patients with extremity tumors (10 bone tumors and 10 soft tissue sarcomas [STS]) who underwent hip disarticulation. Patients treated for hip disarticulation with synchronous femoral vein ligation (n = 10, regular surgery group) and hip disarticulation with delayed femoral vein ligation (n = 10, delayed ligation group), respectively, were enrolled in this study. The operative time and blood loss were used to evaluate the clinical outcomes. The delayed ligation group had significantly lower operative times than the regular surgery group (P < 0.05). Total, hidden, and intraoperative blood loss were all significantly lower in the delayed ligation group than in the regular surgery group (P < 0.05). However, there were no significant differences in postoperative blood loss. In conclusion, delayed femoral vein ligation could significantly reduce the operative time, hidden blood loss, and intraoperative blood loss in patients undergoing hip disarticulation.

Plasma metabolomics in a deep vein thrombosis rat model based on ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry

深静脉血栓(DVT)是一种血栓栓塞性疾病,具有高发病率、高死亡率和高后遗症3大特点。采用左股静脉不完全结扎加高渗盐水刺激建立DVT大鼠模型,使用超高效液相色谱-静电场轨道阱高分辨质谱(UHPLC-Orbitrap HRMS)检测假手术组与DVT模型组的血浆代谢谱,用主成分分析(PCA)及正交偏最小二乘-判别分析(OPLS-DA)对代谢组数据进行多元统计分析,观察两组间的代谢表型差异,将多变量模型分析中的变量重要性值(VIP>1)以及代谢物在模型组中的变化倍数(FC≤0.5或FC≥2,且P<0.05)作为差异代谢物筛选条件。最终在DVT模型组与假手术组间筛选得到27种差异代谢物,这些代谢物反映了DVT大鼠的代谢紊乱情况。具体表现为与假手术组相比,DVT模型组中三甲基胺氮氧化物(TMAO)、维生素K、鹅去氧胆酸、牛磺酸、1-甲基烟酰胺、7-酮胆固醇、反式十六烷基-2-烯醇肉碱、乙烯基乙酰甘氨酸、丙酰脯氨酸、咪唑乙酸、咪唑乙酸核糖苷、1,3,7-三甲基尿酸、1-丁胺、2-羟基异丙酸、吡哆醛、5α-四氢皮质酮、苯乳酸的水平显著升高;而3-脱氢肉碱、磷脂酰胆碱22∶6/20∶2(PC 22∶6/20∶2)、甘油二酯18∶3/20∶4(DG 18∶3/20∶4)、溶血磷脂酰胆碱20∶2(LysoPC 20∶2)、波维酸、鹅肌肽、L-肌肽、辛酸、羟基丙酮酸、3-羟基癸酸的水平显著降低。基于京都基因与基因组百科全书数据库(KEGG)代谢通路的差异丰度(DA)分析显示DVT模型大鼠与假手术组的代谢通路差异主要集中在初级胆汁酸生物合成、胆汁分泌、组氨酸代谢、亚油酸代谢、甘油磷脂代谢和β-丙氨酸代谢。紊乱的代谢物和代谢途径可为进一步深入理解DVT的病理机制、寻找诊断标志物及药物作用靶点提供参考。

Femoral Vein Ligation in an Elderly Patient with a Popliteal Venous Aneurysm: A Case Report

Femoral Vein Ligation in an Elderly Patient with a Popliteal Venous Aneurysm: A Case Report

Two Stage Intravital Imaging Mouse Model to Assess Venous Thromboembolism in Sickle Cell Disease

Sickle cell disease (SCD) patients have an increased risk of venous thromboembolism (VTE). Population-based studies demonstrated that VTE has a cumulative incidence rate of approximately 25% in adult SCD patients and is associated with higher risk of mortality. VTE in SCD is most commonly manifested as deep vein thrombosis (DVT) with associated pulmonary embolism (PE). Although autopsy studies have regularly discovered pulmonary thromboembolic lesions in SCD patients, the pathophysiology of VTE in SCD remains largely unknown mostly due to the lack of relevant animal VTE model. Understanding the mechanisms that promote VTE in SCD is imperative to identify its prevention and treatment measures.To elucidate the cellular, molecular and biophysical mechanisms of VTE in SCD we developed an innovative two stage intravital imaging analysis experimental model in SCD mice. DVT in SCD mice was induced by surgical ligation of femoral vein. Venous thrombus formation was visualized using intravital multi-photon-excitation (MPE) microscopy. Venous thrombus took the form of a large mass of elliptical shape which extended in the long-axis direction of the femoral vein. It was composed of fibrin, erythrocytes and sparse platelets. Over time, thrombus was infiltrated by migrating neutrophils. To trigger acute PE, femoral vein ligation was removed and the venous thrombus was observed to spontaneously detach and travel to the SCD mouse lung. This method allowed real time visualization of acute PE in vivo using MPE microscopy of intact lung in live breathing mice. Acute PE involved embolization of the pulmonary arterioles and the arteriolar bottle-necks located at the junction of pulmonary arterioles and capillaries. The embolization of arteriolar circulation led to loss of blood flow in the arterioles and the down-stream capillaries.Herein we introduce an intravital microscopy approach to probe VTE in SCD live mouse. Our model has potential application in investigating the molecular determinants of VTE associated with SCD as well as evaluating efficacy of new antithrombotic drugs. DisclosuresSundd: Bayer: Research Funding; CSL Behring Inc: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

EP.FRI.42 REBOA associated iatrogenic AV fistula

Abstract Aim To discuss a rarely reported complication of Resuscitative endovascular balloon occlusion of the aorta (REBOA) in a trauma patient with exsanguating haemorrhage. Case description A 15 year old male sustained was brought in as a cod Red, following multiple stab injuries to his Rt thigh. A REBOA was inserted via the contralateral Femoral artery on the scene to control the bleeding. Once proximal and distal control was obtained on the Right leg, the REBOA was deflated and removed. The right leg needed an interposition vein graft and ligation of femoral vein. The patient had received 12 units of transfusion. Post-operative CT-angiogram demonstrated an AV fistula between the Left Profunda femoris artery and Common femoral vein on the side of REBOA insertion. A Duplex scan showed flows of 2600ml/min on duplex and AVF diameter of 2.6mm. It was decided to wait for spontaneously closure as patient underwent rehab. At 6 weeks the AVF flow had reduced to 460ml/min however further expectant management did not lead to spontaneous closure of the AVF and he underwent surgical tie off during his next school holidays 6 months later. Conclusion AV fistula formation as a complication of REBOA insertion has not been reported in paediatric population. It highlights the need for a CT angio after surgical stabilisation. These post traumatic AVFs may need surgical repair if it does not spontaneously close in 3-6 month time.

COMPARISON OF LONG-TERM RESULTS OF FEMORAL VEIN LIGATION AND TRANSCATHETER THROMBOLYSIS IN THROMBOSIS OF THE FEMORAL SEGMENT

INTRODUCTION. The problem of preventing massive pulmonary thromboembolism and post-thrombotic syndrome in deep vein thrombosis has been studied for a long period. The introduction of new treatments for deep vein thrombosis requires a detailed comparison of their effectiveness.The OBJECTIVE of this work was a comparative analysis of ligation of the superficial femoral vein and regional thrombolytic therapy.MATERIAL AND METHODS. A retrospective multicenter study involving 30 patients with femoproplite thrombosis, who had received catheter-directed thrombolysis or ligation of the superficial femoral vein, was performed. The investigated patients underwent inpatient treatment.RESULTS. The data on the effectiveness of both methods in preventing pulmonary thromboembolism were obtained. When comparing both groups, we revealed a statistically significant difference in the frequency of the development of PTS and the severity of its development in 1 year after treatment. With ligation vein, 73.3 and 6.7% in the thrombolysis group (p=0.0005).CONCLUSION. Regional thrombolysis was an effective treatment for deep vein thrombosis and prevention of PTS.The authors declare no conflict of interest.The authors confirm that they respect the rights of the people participated in the study, including obtaining informed consent when it is necessary, and the rules of treatment of animals when they are used in the study. Author Guidelines contains the detailed information.

Treatment of popliteal venous aneurysms by femoral vein ligation

Popliteal venous aneurysms are highly associated with local venous thrombosis and pulmonary embolism. We propose a simple and new surgical therapy for popliteal venous aneurysm by ligation of the femoral vein. We describe the case of a woman with recurrent pulmonary embolism. Venous ultrasound examination showed a venous aneurysm of the right popliteal fossa. We proposed a ligature-section of the femoral vein just below the confluence of the great saphenous vein. After >6 years of follow-up, the patient is asymptomatic, with a completely normal life and only a small amount of edema of the right leg.

Abstract 16598: Carnosine Synthetase Overexpression in Skeletal Muscle Promotes Functional Recovery of Ischemic Limb

Carnosine synthetase (ATPGD1) is an ATP grasp enzyme that catalyzes formation of histidyl dipeptides such as carnosine (β-alanine-histidine) and anserine (β-alanine-methyl histidine). These dipeptides are food constituents found in a high concentration in the skeletal muscle (10-20 mM) that have the abilities to chelate metals, scavenge lipid peroxidation products and buffer intracellular pH. These dipeptides are regarded as protective against injury and stress. Despite this knowledge, whether carnosine regulates angiogenesis is unknown. To assess this potential, a model of hindlimb ischemia (HLI) was surgically induced by femoral artery and vein ligation in the C57BL/6J (wild type, WT) mice provided drinking water without or with carnosine (1g/L) for 21 days post-surgery. C57BL/6J WT mice subjected to HLI and supplemented with carnosine had increased skeletal muscle expression of the dipeptide/histidine transporter (PHT1), carnosine transport, improved blood flow recovery, re-vascularization and regeneration of myocytes in the ischemic limb compared with mice without carnosine. To support that elevated skeletal muscle carnosine was beneficial in HLI, transgenic mice overexpressing ATPGD1 in the skeletal muscle were constructed. Transgenic (α-HSA-ATPGD1TG) mice had ~2-2.5-fold increase in carnosine (WT: 2.71±0.54 vs 7.40±0.54 nmoles/mg protein α-HSA-ATPGD1TG; p &lt;0.05) and anserine levels (WT: 3.65±1.12 vs 8.04±0.23 nmoles/mg protein α-HSA-ATPGD1TG p &lt;0.05) in the skeletal muscle than WT mice. At 2 and 3 weeks post-HLI surgery, α-HSA-ATPGD1TG mice had significantly improved blood flow recovery compared with the WT mice (2 weeks: α-HSA-ATPGD1TG: 59±3% vs 45±3% WT; p &lt;0.05; 3 weeks: α-HSA-ATPGD1TG: 65±4% vs 46±2% WT; p &lt;0.05). Because faster recovery of blood flow in the carnosine-supplemented mice was accompanied with increased expression of hypoxia inducible factor (HIF-1α) and vascular endothelial factor (VEGF) in the ischemic limb, we further investigated the mechanistic connection. Skeletal muscle myoblasts C2C12 cells pretreated with octyl-D-carnosine and subjected to 1 h of hypoxia, replacing oxygen with 95% N 2 and 5% CO 2 , had enhanced HIF-1α translocation, VEGF mRNA and secretion compared with untreated hypoxic and normoxic cells. Collectively, our results demonstrate that carnosine improves ischemia-stimulated angiogenesis potentially by stabilizing HIF1-α and promoting VEGF formation suggesting that carnosine may be a useful therapy in critical limb ischemia.

Profilaxis of pulmonary embolism with transfascial thrombosis

The aim — to substantiate indices to surgery prophylaxis of pulmonary embolism related to transfascial thrombosis in the inferior vena cava system.Materials and methods. The results of examination and surgery treatment of 125 patients with transfascial thrombosis have been analyzed, patients were admitted to surgical diseases department of Novak clinical hospital of Transcarpathia region in the period from 1995 to 2014. These were 47 (37.6 %) men and 78 (62.4 %) women. The age of the patients ranged from 16 to 83 years, the mean age was 53 ± 2.5 years. The frequency of transfascial thrombosis among the total number of treated patients (n = 1601) for acute varicotromboflebitis during the mentioned period was 7.8 % of cases. Patients underwent laboratory and instrumental examination, ultrasound Doppler and ultrasound duplex scanning (Aloka­3500, Japan; My Lab­50, Italy; HDI­1500 ATL­Philips; Ultima Pro­30, z.one Ultra, Zonare Medical Systems Inc., USA).Results and discussion. In 62 (49.6 %) patients, the proliferation of thrombotic process on the deep venous system was observed in the area of sapheno­femoral junction with the transition on the common femoral vein, the length of floating part of the thrombotic masses varied from 1.5 to 7.5 cm, on average 4.2 ± 0.7 cm. In 54 (87.1 %) patients, when spreading the floating top of thrombotic masses beyond the boundaries of sapheno­femoral junction of 3 cm length, thrombectomy was performed through the large subcutaneous vein orifice at the height of Valsalva test. 8 (12.9 %) patients underwent a venotomical section of the general femoral vein for thrombectomy. In 20 (16.0 %) patients, the spread of thrombotic process on the deep venous system was observed in the region of sapheno­popliteal junction with the transition to the popliteal vein. The length of floating part the thrombotic mass in spreading through the sapheno­popliteal junction varied from 1.5 to 5.5 cm, on average of 3.3 ± 0.5 cm. In 15 (75.0 %) patients it was possible to perform the thrombectomy from the popliteal vein through the orifice of the small subcutaneous vein. In 5 (25.0 %) patients were performed the venotomy of popliteal vein during thrombectomy. The transition of thrombotic lesion through the perforated veins of the shin was detected in 43 (34.4 %) patients. In this case, the localization of the top thrombotic masses in the shin veins was observed in 7 (16.3 %), in the leaf veins — in 16 (37.2 %), in the popliteal veins — in 17 (39.5 %) and in the surface popliteal veins — in 3 (7.0 %) patients. In 7 patients with localization on the top of thrombotic masses in the perforated vein, thrombectomy was performed from the perforated vein during the compression of the calf muscles and the ligation of the perforated vein. In 7 patients the ligation of the popliteal vein below the fall of the small subcutaneous vein was performed in order to prevent pulmonary embolism for the transition of thrombotic masses through the perforated veins on the shin. In 26 patients an open thrombectomy from the popliteal vein or the calf venous sinus with venotomy followed by ligation of affected venous sinuses was performed. In 3 patients with the spreading the process on popliteal and superficial femoral veins, the ligation of the superficial femoral veins below the fall of issue of the deep femoral vein was performed.Conclusions. In order to prevent the pulmonary thrombosis, the volume of surgical intervention should be extended. Patients with transfascial thrombosis, regardless the surgery redicality, should be treated as in the case of deep vein thrombosis.

Intramuscular E-selectin/adeno-associated virus gene therapy promotes wound healing in an ischemic mouse model

BackgroundPoor wound healing in critical limb ischemia (CLI) is attributed to impaired neovascularization and reperfusion. Optimizing the ischemic wound with adhesion molecules that enhance stem cell homing may revolutionize treatment. The purpose of this study is to test the efficacy of adhesion molecule E-selectin on wound healing in an ischemic mouse wound. MethodsAdult FVB/NJ mice underwent unilateral femoral artery and vein ligation to induce CLI. A 4-mm punch biopsy wound was created on the anterior thigh to simulate ischemic wounds. Intramuscular injection of adeno-associated virus (AAV) carrying either E-selectin (E-selectin/AAV, n = 11) or LacZ as control (LacZ/AAV, n = 10) was performed. Gross wound size was measured for 10 d postoperatively. Ischemic hindlimb reperfusion was quantified using laser Doppler imaging. Wound tissue neovascularization was visualized using DiI perfusion and confocal microscopy. E-selectin expression in wounds was verified by immunofluorescence. ResultsImmunofluorescence confirmed E-selectin/AAV delivery in treatment versus control limbs. Wounds from E-selectin/AAV mice versus controls revealed surface area healing of 54% versus 20% (P < 0.01) on postoperative day (POD) 1, 78% versus 51% on POD 4 (P < 0.01), and 97% versus 84% on POD 10 (P < 0.01). Laser Doppler imaging revealed greater reperfusion in E-selectin/AAV mice versus controls by POD 10 (0.49 versus 0.27, P < 0.05). DiI perfused ligated hindlimb in E-selectin/AAV versus control mice revealed mean neovascularization intensity score of 30 versus 18 (P < 0.05) on POD 10. ConclusionsIntramuscularly injected E-selectin/AAV gene therapy in mice with CLI significantly increases wound angiogenesis and limb reperfusion, expediting overall wound healing.

"…in every…art, fundamental matters are perennially being discovered, discredited, forgotten, rediscovered and reaffirmed".

In this first issue of 2018, we are happy to provide the readership of Clinical Anatomy a Special Issue on Ocular Trauma. This issue was organized by Dr. Arne Viestenz of the Department of Ophthalmology, Martin-Luther-University Halle-Wittenberg. Other articles of interest in this issue include papers on body donation, the facial artery and a new substitute for formalin. The title of this editorial is attributed to surgeon John Homans (Fig. 1) who was born in 1877 in Boston. He was educated at Harvard and his initial residency training was at Massachusetts General Hospital. Homans trained with Halsted and Cushing (Barker, 1999). After experiences in Baltimore and London, in 1912, he returned to Boston to join Cushing at the new Peter Bent Brigham Hospital. Late in his career, he spent a year at Yale University as the Carmalt Visiting Professor. Interestingly, one of Homans’ ancestors had been surgeon general to George Washington. John Homans (1877–1954) Homans later worked on peripheral vascular disease, helping to popularize the ligation of the saphenofemoral junction for treatment of varicose veins, and advocating ligation of the superficial femoral vein to stop migrating clots causing pulmonary embolus. He described the sign which bears his name in 1944, and reported the first instance of deep venous thrombosis occurring in flight in 1954 (the same year as his death) in a doctor who had flown between Boston and Caracas (Barker, 1999). He was also interested in lymphedema, developing the Homans operation for this condition. Homans’ sign is a sign of deep vein thrombosis and defined as discomfort behind the knee on forced dorsiflexion of the foot. It was later redefined as “discomfort need have no part in the reaction”, including increased resistance, involuntary flexure of the knee or pain in the calf to forced dorsiflexion as positive responses.

Endothelial colony forming cells and mesenchymal progenitor cells form blood vessels and increase blood flow in ischemic muscle

Here we investigated whether endothelial colony forming cells (ECFC) and mesenchymal progenitor cells (MPC) form vascular networks and restore blood flow in ischemic skeletal muscle, and whether host myeloid cells play a role. ECFC + MPC, ECFC alone, MPC alone, or vehicle alone were injected into the hind limb ischemic muscle one day after ligation of femoral artery and vein. At day 5, hind limbs injected with ECFC + MPC showed greater blood flow recovery compared with ECFC, MPC, or vehicle. Tail vein injection of human endothelial specific Ulex europaeus agglutinin-I demonstrated an increased number of perfused human vessels in ECFC + MPC compared with ECFC. In vivo bioluminescence imaging showed ECFC persisted for 14 days in ECFC + MPC-injected hind limbs. Flow cytometric analysis of ischemic muscles at day 2 revealed increased myeloid lineage cells in ECFC + MPC-injected muscles compared to vehicle-injected muscles. Neutrophils declined by day 7, while the number of myeloid cells, macrophages, and monocytes did not. Systemic myeloid cell depletion with anti-Gr-1 antibody blocked the improved blood flow observed with ECFC + MPC and reduced ECFC and MPC retention. Our data suggest that ECFC + MPC delivery could be used to reestablish blood flow in ischemic tissues, and this may be enhanced by coordinated recruitment of host myeloid cells.

Abstract 41: Implantable Oxygen Biosensor Reveals Post-Occlusion Tissue Reactive Hyperoxia

INTRODUCTION: This study utilized an implantable biosensor to measure tissue oxygenation before, during, and after a transient ischemic insult. The purpose of this study was to use implantable O2 sensors to quantify local O2 content following ischemic challenges and perfusion restoration. METHODS: All animals were treated according to approved IACUC protocols. First, rats were subjected to unilateral femoral artery and vein ligation and received bilateral biosensor implants in the hind limbs. The biosensors were composed of a porphyrin embedded into a porous poly-hydroxyethylmethacrylate (pHEMA) scaffold and were injected through an 18-gauge needle into the subcutis. The biosensor’s phosphorescence lifetime changed inversely with O2 concentration. Near infrared spectroscopy (NIR) was also used to quantify percent O2 saturation of hemoglobin at the tissue level. Laser Doppler flowmetry was used to quantify blood flow. On post-operative days 28 and 84, the rats underwent a series of systemic hypoxic challenges as well as bilateral hind limb tourniquet application. Response magnitudes, response times and normalized changes were calculated for comparison between techniques. Statistical significance was assessed using ANOVA and two-sample paired t-test at p-value < 0.05. RESULTS: Laser Doppler flowmetry confirmed a reactive hyperemia following tourniquet release. In addition, both the phosphorescence lifetime biosensor and NIR methods suggested that the tissue O2 content temporarily but significantly exceeded baseline following tourniquet release (p<0.05). We term this phenomenon reactive hyperoxia. This suggests that the O2 supply transiently exceeds oxygen consumption. Even though tissue O2 consumption was expected to be elevated following ischemia to repay the O2 debt developed during occlusion, the elevated O2 content indicates that the increased consumption is met with an even greater elevated O2 supply. The NIR spectroscopy and phosphorescence lifetime data are consistent. The phosphorescence lifetime biosensor also demonstrates a more prominent response magnitude in general and a faster response over time (71 secs vs. 143 secs in NIR; p = 0.0053), suggesting that the sensing elements may have gained greater proximity to the blood supply via vascular ingrowth through the porous pHEMA scaffold. CONCLUSION: The implantable phosphorescence lifetime biosensor provided real time monitoring of tissue oxygenation, with a rapid and prominent response, excellent biocompatibility and highly localized measurements. Both the phosphorescence lifetime and NIR spectroscopy techniques demonstrated a reactive hyperoxia post ischemia. Direct assessment of tissue oxygenation may provide helpful diagnostic and prognostic information on wound healing, re-vascularization, 3D scaffold design and efficacy of therapeutics promoting tissue oxygenation.

Açık inguinal tamir operasyonu esnasında iyatrojenik femoral ven ligasyonununun geç dönem cerrahi tedavisi

Açık inguinal tamir operasyonu esnasında iyatrojenik femoral ven ligasyonununun geç dönem cerrahi tedavisi

Radiolabeled tirofiban - a potential radiopharmaceutical for detection of deep venous thrombosis.

AimThe aim of this study was to investigate the possibility of using 99mtechnetium (99mTc)-labeled tirofiban (a reversible antagonist of glycoprotein IIb/IIIa) for detection of deep venous thrombosis (DVT) in rats without causing an antiplatelet effect.MethodsThe ability of in vitro tirofiban to inhibit adenosine 5′-diphosphate (ADP)-induced platelet aggregation was evaluated using optical aggregometer. Binding of 99mTc-tirofiban to platelets was evaluated. Serum levels of unlabeled (a validated high performance liquid chromatography method) and 99mTc-tirofiban after single intravenous injection were evaluated in male Wistar rats with or without induced DVT (femoral vein ligation model), and the rats were also subjected to whole body scintigraphy.ResultsTirofiban in vitro inhibits ADP-induced aggregation of human platelets in a dose- and concentration-dependent manner (10 nM to 2 μM), but only if it is added before ADP and not after ADP. 99mTc labeling did not affect the ability of tirofiban to bind to either human or rat platelets, nor did it affect tirofiban pharmacokinetics in intact rats or in animals with induced DVT. When 99mTc-tirofiban was injected to rats after induction of DVT, at a molar dose lower than the one showing only a weak antiaggregatory effect in vitro, whole body scintigraphy indicated localization of 99mTc-tirofiban around the place of the induced DVT.Conclusion99mTc labeling of tirofiban does not affect its ability to bind to glycoprotein IIb/IIIa or its in vivo pharmacokinetics in rats, either intact or with DVT. A low, nonantiaggregatory dose of 99mTc-tirofiban may be used to visualize DVT at an early stage.

Surgical techniques for hemostasis in penetrating trauma to femoral artery

Objectives: To analyse the efficacy of various operative procedures and factors affecting the outcome especially the effect of limb ischemia time in penetrating trauma to the femoral artery. Study Design: Prospective. Setting: Study was conducted at West Surgical Ward, Mayo Hospital Lahore. Duration: August 2001 to July 2004. Materials and Methods: All the patients &gt;12 years of age referred from periphery as well as directly admitted with penetrating trauma to the femoral vessels alone or associated with other organ injuries having hard/soft physical signs of an arterial injury were included in the study. Results: 39(97.5%) patients were male, age ranged from 14-53 years with the mean limb ischemia time of 7.8 hours in the series. 35(87.5%) patients sustained firearm injuries. Superficial femoral artery was injured in 23(57.5%) followed by vein in 12(30%) and major vessels were found intact in 4(10%) patients. Lateral arteriorrhaphy was performed in 4(10%) &amp; venorrhaphy in 3(7.5%) patients with 100 % succ ess rate, resection and primary anastomosis in 18(45%) patients with pseudo aneurysm formation in 1(2.5%) patient. Reverse great saphenous vein graft was interposed in 9(22.5%) patients with graft failure rate of 5% (2 patients). Femoral vein was ligated in 12(30%) patients with development of deep vein thrombosis in 2(5%) patients. There were 3(7.5%) deaths. No synthetic graft was used in the series. Conclusion: Exsanguination, prolonged injury duration, associated organ injuries and extensive soft tissue and skin damage of the extremities were the major factors responsible for increased morbidity particularly limb loss and mortality. Proximity of injury to the femoral vessels was a poor predictor of an arterial injury in the study. Arteriorrhaphy and primary end-to-end anastomosis are the main stays for an arterial injury repair, next comes the use of autogenous vein graft, in our setup. Moreover ligation of femoral vein is not associated with leg amputation.

Abstract 15705: Chronic Inhaled Acrolein Depresses Circulating Endothelial Progenitor Cells and Promotes Atherosclerosis

We have previously shown that acute exposure to air pollutants including particulate matter or the volatile acrolein leads to reversible suppression of circulating angiogenic cells in humans and mice. Exposure to tobacco smoke, which contains both particles and aldehydes such as acrolein, also suppresses EPC number and function in association with an increase in cardiovascular disease risk. To assess whether acrolein alone worsened vascular pathogenesis, we exposed mice to acrolein (1 ppm * 6h/day) in a murine model of hind limb ischemia. Mice were exposed to acrolein for 4 days prior to permanent right femoral artery and vein ligation and bisection (distal to inguinal ligament) with continued exposure to filtered air (control) or acrolein for another 2 weeks. Blood flow recovery in the ischemic hind limb was measured via Laser Doppler Perfusion Imaging (LDPI) and normalized as a percentage of flow in the non-ischemic limb. Although acute exposure to acrolein reduced the number of circulating angiogenic cells it had only a modest effect blood flow recovery after 7 days (% Recovery: air, 86.2±21.4; acrolein, 68.3±21.6, n=8,8, p=0.12). Hence to determine whether chronic acrolein exposure worsened chronic vascular injury, we exposed C57BL/6J mice to 1 ppm acrolein for 12 weeks. This long-term exposure significantly depressed (by 51%) circulating levels of Flk-1+/Sca-1+ cells (as % of lymphocytic counts: air 0.15±0.09; acrolein 0.07±0.05; p&lt;0.02). To tested if cell changes were associated with changes in atherogenesis, apoE-null mice on normal chow or high-fat diet were exposed to chronic acrolein (1 ppm; 12 week). Acrolein accelerated aortic atherosclerosis by 1.6-fold (p&lt;0.001) but it did not affect coincident dyslipidemia (total cholesterol: air, 1224±189; acrolein, 1076±195 mg/dL) compared with air-exposed, HFD-fed mice. These results suggest that that chronic low level acrolein exposure suppresses circulating angiogenic cells and accelerates atherogenesis; hence the atherogenic effect of exposure to traffic pollutants, indoor smoke or cigarette smoke may be in part attributable to acrolein. These findings could inform exposure risk assessments and the development of new policies for regulating pollutant exposure and tobacco product use.

Elevated Prothrombin Promotes Venous, but Not Arterial, Thrombosis in Mice

Individuals with elevated prothrombin, including those with the prothrombin G20210A mutation, have increased risk of venous thrombosis. Although these individuals do not have increased circulating prothrombotic biomarkers, their plasma demonstrates increased tissue factor-dependent thrombin generation in vitro. The objectives of this study were to determine the pathological role of elevated prothrombin in venous and arterial thrombosis in vivo, and distinguish thrombogenic mechanisms in these vessels. Prothrombin was infused into mice to raise circulating levels. Venous thrombosis was induced by electrolytic stimulus to the femoral vein or inferior vena cava ligation. Arterial thrombosis was induced by electrolytic stimulus or ferric chloride application to the carotid artery. Mice infused with prothrombin demonstrated increased tissue factor-triggered thrombin generation measured ex vivo, but did not have increased circulating prothrombotic biomarkers in the absence of vessel injury. After venous injury, elevated prothrombin increased thrombin generation and the fibrin accumulation rate and total amount of fibrin ≈ 3-fold, producing extended thrombi with increased mass. However, elevated prothrombin did not accelerate platelet accumulation, increase the fibrin accumulation rate, or shorten the vessel occlusion time after arterial injury. These findings reconcile previously discordant findings on thrombin generation in hyperprothrombinemic individuals measured ex vivo and in vitro, and show elevated prothrombin promotes venous, but not arterial, thrombosis in vivo.

Nitrite anion stimulates ischemic arteriogenesis involving NO metabolism

Nitric oxide (NO) is a potential regulator of ischemic vascular remodeling, and as such therapies augmenting its bioavailability may be useful for the treatment of ischemic tissue diseases. Here we examine the effect of administering the NO prodrug sodium nitrite on arteriogenesis activity during established tissue ischemia. Chronic hindlimb ischemia was induced by permanent unilateral femoral artery and vein ligation. Five days postligation; animals were randomized to control PBS or sodium nitrite (165 μg/kg) therapy twice daily. In situ vascular remodeling was measured longitudinally using SPY angiography and Microfil vascular casting. Delayed sodium nitrite therapy rapidly increased ischemic limb arterial vessel diameter and branching in a NO-dependent manner. SPY imaging angiography over time showed that nitrite therapy enhanced ischemic gracillis collateral vessel formation from the profunda femoris to the saphenous artery. Immunofluorescent staining of smooth muscle cell actin also confirmed that sodium nitrite therapy increased arteriogenesis in a NO-dependent manner. The NO prodrug sodium nitrite significantly increases arteriogenesis and reperfusion of established severe chronic tissue ischemia.