Regional and Conducted Vascular Effects of Endovascular Ultrasound Catheters.

Intra-vascular ultrasound catheters are used clinically to facilitate clot lysis. We hypothesized that these devices could also directly lower microvascular resistance and increase tissue perfusion through established shear-dependent pathways. In mice, either the proximal hind-limb muscles or the upstream femoral artery alone was exposed to an endovascular ultrasound catheter (2.3 MHz, 0.5-1.1 MPa) for 10 min. Quantitative microvascular perfusion imaging in the hind limbs exposed to the endovascular ultrasound system exhibited a more-than-twofold increase in flow (p < 0.01) compared with the contralateral control limb after exposure of either the muscle or the femoral artery alone. Using an in vivo optical imaging reporting system, an eight- to ninefold increase in tissue adenosine triphosphate (ATP) was detected in the region of insonification (p = 0.006). Ultrasound was found to produce an immediate release of ATP from ex vivo erythrocytes (p = 0.03). In situ electrochemical sensing revealed an immediate increase in nitric oxide with initiation of ultrasound which returned to baseline within 5 min of termination, as well as ultrasound-triggered nitric oxide (NO) release from erythrocytes. These data indicate that non-cavitating ultrasound produced by endovascular catheters can reduce vascular resistance and increase flow through recognized shear-dependent vasodilator pathways involving purinergic signaling and NO.

Mouse laser injury models: variations on a theme.

A confluence of technological advances in genetic manipulation and molecular-based fluorescence imaging has led to the widespread adoption of laser injury models to study hemostasis and thrombosis in mice. In all animal models of hemostasis and thrombosis, detailing the nature of experimentally induced vascular injury is paramount in enabling appropriate interpretation of experimental results. A careful appraisal of the literature shows that direct laser-induced injury can result in variable degrees of vascular damage. This review will compare and contrast models of laser injury utilized in the field, with an emphasis on the mechanism and extent of injury, the use of laser injury in different vascular beds and the molecular mechanisms regulating the response to injury. All of these topics will be discussed in the context of how distinct applications of laser injury models may be viewed as representing thrombosis and/or hemostasis.

High dose-rate brachytherapy for the treatment of lower extremity in-stent restenosis.

OBJECTIVE: Historically, edge stenosis and late thrombosis limited the effectiveness of adjunctive endovascular brachytherapy (EVBT) for in-stent restenosis (ISR) after percutaneous transluminal angioplasty (PTA) and stenting. We evaluated an updated protocol of PTA and EVBT for ISR among patients with lower extremity occlusive disease. METHODS: This is a retrospective, single-center review of patients treated with PTA and EVBT for ISR in the iliac and femoropopliteal segments between 2004 and 2012. A dose of 20 Gy was given at a depth of 0.5 mm beyond the radius of the largest PTA balloon using iridium 192, with at least 2-cm-long margins of radiation coverage proximal and distal to the injured area. Stents were assessed for patency by duplex ultrasound imaging at 1, 3, 6, 9, 12, and 18 months and then yearly. The primary end point was freedom from ≥50% restenosis in the treated segment at 6 months, 1 year, and 2 years. Patency data were estimated using the Kaplan-Meier method. Secondary end points were early and late thrombotic occlusion. RESULTS: Among 42 consecutive cases in 35 patients of EVBT for ISR in common or external iliac (9 [20.8%]) and superficial femoral or popliteal (33 [76.7%]) arteries, or both, 21 patients (50%) had claudication, asymptomatic hemodynamically significant stenoses were identified on duplex ultrasound imaging in 16 (38.1%), and 4 (9.8%) had critical limb ischemia. Mean treated length was 23.5 ± 12.3 cm over a mean duration of 16.1 ± 9.6 minutes. There was one technical failure (2.3%). Median post-EVBT follow-up time was 682 days (range, 1-2262 days). There were two (4.9%) and five (11.9%) cases of early and late thrombotic occlusions, respectively. There was one death, believed to be secondary to acute coronary syndrome. Primary, assisted primary, and secondary patency in the entire cohort was 75.2%, 89.1%, and 89.1%, respectively, at 1 year and 63.7%, 80.6%, and 85.6%, respectively, at 2 years. CONCLUSIONS: This contemporary protocol of PTA and adjunctive EVBT for lower extremity ISR, which is updated from those used in prior trials and includes a surveillance strategy that identifies at-risk stents for reintervention before occlusion, may be a promising treatment for lower extremity ISR at institutions where a close collaboration between vascular surgeons and radiation oncologists is feasible.

Impact of Center Experience on Patient Radiation Exposure During Transradial Coronary Angiography and Percutaneous Intervention: A Patient-Level, International, Collaborative, Multi-Center Analysis.

BACKGROUND: The adoption of the transradial (TR) approach over the traditional transfemoral (TF) approach has been hampered by concerns of increased radiation exposure-a subject of considerable debate within the field. We performed a patient-level, multi-center analysis to definitively address the impact of TR access on radiation exposure. METHODS AND RESULTS: Overall, 10 centers were included from 6 countries-Canada (2 centers), United Kingdom (2), Germany (2), Sweden (2), Hungary (1), and The Netherlands (1). We compared the radiation exposure of TR versus TF access using measured dose-area product (DAP). To account for local variations in equipment and exposure, standardized TR:TF DAP ratios were constructed per center with procedures separated by coronary angiography (CA) and percutaneous coronary intervention (PCI). Among 57 326 procedures, we demonstrated increased radiation exposure with the TR versus TF approach, particularly in the CA cohort across all centers (weighted-average ratios: CA, 1.15; PCI, 1.05). However, this was mitigated by increasing TR experience in the PCI cohort across all centers (r=-0.8; P=0.005). Over time, as a center transitioned to increasing TR experience (r=0.9; P=0.001), a concomitant decrease in radiation exposure occurred (r=-0.8; P=0.006). Ultimately, when a center's balance of TR to TF procedures approaches 50%, the resultant radiation exposure was equivalent. CONCLUSIONS: The TR approach is associated with a modest increase in patient radiation exposure. However, this increase is eliminated when the TR and TF approaches are used with equal frequency-a guiding principle for centers adopting the TR approach.

Results of a randomized clinical trial of external beam radiation to prevent restenosis after superficial femoral artery stenting.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of external beam radiation (EBR) in preventing restenosis after superficial femoral artery (SFA) stenting in comparison with a control group treated with SFA stenting only. METHODS: In this Institutional Review Board-approved study, patients who provided written informed consent were randomly assigned to 0 Gy or 14 Gy of EBR to the stent site 24 hours after SFA stenting. The primary end point was the angiographic binary restenosis rate 2 years after stenting. Categorical and continuous end points were respectively analyzed using logistic regression models and Wilcoxon tests. End points expressed as time to event were analyzed using a log-rank test. RESULTS: The study included 155 patients, 46 women and 109 men (mean age, 66 years; range, 45-85 years). In the 0 and 14 Gy groups, binary restenosis was present, respectively, in 44% (34/77) and 68% (52/76; P = .003) 2 years after stenting. Stent thrombosis occurred in 13% (10/78) of the 0 Gy group and in 33% (25/77) of the 14 Gy group (P = .003). Target lesion revascularization at 2 years was 26% (25/78) in the 0 Gy group and 30% (23/77) in the 14 Gy group (P = .56). There were no significant differences in total walking distances change from baseline to 2 years (46 ± 100 and 26 ± 79 m, respectively, in the 0 Gy and 14 Gy group; P = .25). There were no procedure-related deaths and no major amputations. CONCLUSIONS: A single 14 Gy dose of EBR to the SFA stenting site did not prevent in-stent restenosis.

Percutaneous Treatment of Superficial Femoral Artery Stenosis Secondary to Radiation Arteritis.

Radiation arteritis is a rare cause of lower extremity peripheral arterial occlusive disease, and has been traditionally treated with open interventions. There have been only a few reported cases of endovascular interventions for this disease. Previous reports described endovascular treatment in the iliac and common femoral regions, but intervention in the superficial femoral artery have not been described. Described here is a case of acute lower extremity ischemia caused by remote radiation arteritis of the superficial femoral artery, which was successfully treated by percutaneous endovascular technique.

Trans-Stent B-Mode Ultrasound and Passive Cavitation Imaging.

Angioplasty and stenting of a stenosed artery enable acute restoration of blood flow. However, restenosis or a lack of re-endothelization can subsequently occur depending on the stent type. Cavitation-mediated drug delivery is a potential therapy for these conditions, but requires that particular types of cavitation be induced by ultrasound insonation. Because of the heterogeneity of tissue and stochastic nature of cavitation, feedback mechanisms are needed to determine whether the sustained bubble activity is induced. The objective of this study was to determine the feasibility of passive cavitation imaging through a metal stent in a flow phantom and an animal model. In this study, an endovascular stent was deployed in a flow phantom and in porcine femoral arteries. Fluorophore-labeled echogenic liposomes, a theragnostic ultrasound contrast agent, were injected proximal to the stent. Cavitation images were obtained by passively recording and beamforming the acoustic emissions from echogenic liposomes insonified with a low-frequency (500 kHz) transducer. In vitro experiments revealed that the signal-to-noise ratio for detecting stable cavitation activity through the stent was greater than 8 dB. The stent did not significantly reduce the signal-to-noise ratio. Trans-stent cavitation activity was also detected in vivo via passive cavitation imaging when echogenic liposomes were insonified by the 500-kHz transducer. When stable cavitation was detected, delivery of the fluorophore into the arterial wall was observed. Increased echogenicity within the stent was also observed when echogenic liposomes were administered. Thus, both B-mode ultrasound imaging and cavitation imaging are feasible in the presence of an endovascular stent in vivo. Demonstration of this capability supports future studies to monitor restenosis with contrast-enhanced ultrasound and pursue image-guided ultrasound-mediated drug delivery to inhibit restenosis.

Radiation-induced rupture of the superficial femoral artery: a case report.

BACKGROUND: Radiation-induced necrosis and arteriopathy are well-known iatrogenic pathologic entities. However, radiation-induced rupture of the superficial femoral artery is an exceptional life-threatening event. REPORT: We hereby report a case of radiation-induced rupture of the superficial femoral artery that was successfully treated by fascial stitching then by an endovascular approach by stenting. RESULTS: Infection, skin stiffness, and major tissue loss in a previously irradiated field are important limiting factors to an open surgical approach. CONCLUSION: It is important to consider using a combined approach for selected patients.

Irradiated superficial femoral artery rupture after free flap: a case report and review of the literature.

Radical oncologic resection can result in large soft tissue defects with exposure of underlying vessels. Unless immediately covered with viable soft tissue, these vessels are vulnerable to desiccation from air exposure and mechanical trauma. Local radiation treatment also contributes to a decline in vessel wall strength. We present an index case of a patient with prolonged exposure of her femoral bone and superficial femoral artery after an initial failed reconstruction of a soft tissue sarcoma resection defect. We provided coverage using a free latissimus dorsi muscle flap. Two weeks after the initial free flap operation, the patient was readmitted to emergency service with profuse bleeding from beneath the free flap. Intraoperative inspection revealed a 2-cm defect of the irradiated superficial femoral artery. The defect was repaired with cryopreserved human arterial graft, and the flap was reset. This case highlights the importance of immediate coverage of soft tissue defects after oncologic resection. If any vessels are left exposed, they should be closely inspected before a delayed flap coverage to rule out future sources of bleeding that may jeopardize the outcomes of an otherwise successful free flap operation.

Radiation safety and vascular access: attitudes among cardiologists worldwide.

OBJECTIVES: To determine opinions and perceptions of interventional cardiologists on the topic of radiation and vascular access choice. BACKGROUND: Transradial approach for cardiac catheterization has been increasing in popularity worldwide. There is evidence that transradial access (TRA) may be associated with increasing radiation doses compared to transfemoral access (TFA). METHODS: We distributed a questionnaire to collect opinions of interventional cardiologists around the world. RESULTS: Interventional cardiologists (n=5332) were contacted by email to complete an on-line survey from September to October 2013. The response rate was 20% (n=1084). TRA was used in 54% of percutaneous coronary interventions (PCIs). Most TRAs (80%) were performed with right radial access (RRA). Interventionalists perceived that TRA was associated with higher radiation exposure compared to TFA and that RRA was associated with higher radiation exposure that left radial access (LRA). Older interventionalists were more likely to use radiation protection equipment and those who underwent radiation safety training gave more importance to ALARA (as low as reasonably achievable). Nearly half the respondents stated they would perform more TRA if the radiation exposure was similar to TFA. While interventionalists in the United States placed less importance to certain radiation protective equipment, European operators were more concerned with physician and patient radiation. CONCLUSIONS: Interventionalists worldwide reported higher perceived radiation doses with TRA compared to TFA and RRA compared to LRA. Efforts should be directed toward encouraging consistent radiation safety training. Major investment and application of novel radiation protection tools and radiation dose reduction strategies should be pursued.

Far red/near infrared light treatment promotes femoral artery collateralization in the ischemic hindlimb.

Nitric oxide (NO) is a crucial mediator of hindlimb collateralization and angiogenesis. Within tissues there are nitrosyl-heme proteins which have the potential to generate NO under conditions of hypoxia or low pH. Low level irradiation of blood and muscle with light in the far red/near infrared spectrum (670 nm, R/NIR) facilitates NO release. Therefore, we assessed the impact of red light exposure on the stimulation of femoral artery collateralization. Rabbits and mice underwent unilateral resection of the femoral artery and chronic R/NIR treatment. The direct NO scavenger carboxy-PTIO and the nitric oxide synthase (NOS) inhibitor L-NAME were also administered in the presence of R/NIR. DAF fluorescence assessed R/NIR changes in NO levels within endothelial cells. In vitro measures of R/NIR induced angiogenesis were assessed by endothelial cell proliferation and migration. R/NIR significantly increased collateral vessel number which could not be attenuated with L-NAME. R/NIR induced collateralization was abolished with c-PTIO. In vitro, NO production increased in endothelial cells with R/NIR exposure, and this finding was independent of NOS inhibition. Similarly R/NIR induced proliferation and tube formation in a NO dependent manner. Finally, nitrite supplementation accelerated R/NIR collateralization in wild type C57Bl/6 mice. In an eNOS deficient transgenic mouse model, R/NIR restores collateral development. In conclusion, R/NIR increases NO levels independent of NOS activity, and leads to the observed enhancement of hindlimb collateralization.

Transient repetitive exposure to low level light therapy enhances collateral blood vessel growth in the ischemic hindlimb of the tight skin mouse.

The tight skin mouse (Tsk(-/+)) is a model of scleroderma characterized by impaired vasoreactivity, increased oxidative stress, attenuated angiogenic response to VEGF and production of the angiogenesis inhibitor angiostatin. Low-level light therapy (LLLT) stimulates angiogenesis in myocardial infarction and chemotherapy-induced mucositis. We hypothesize that repetitive LLLT restores vessel growth in the ischemic hindlimb of Tsk(-/+) mice by attenuating angiostatin and enhancing angiomotin effects in vivo. C57Bl/6J and Tsk(-/+) mice underwent ligation of the femoral artery. Relative blood flow to the foot was measured using a laser Doppler imager. Tsk(-/+) mice received LLLT (670 nm, 50 mW cm(-2), 30 J cm(-2)) for 10 min per day for 14 days. Vascular density was determined using lycopersicom lectin staining. Immunofluorescent labeling, Western blot analysis and immunoprecipitation were used to determine angiostatin and angiomotin expression. Recovery of blood flow to the ischemic limb was reduced in Tsk(-/+) compared with C57Bl/6 mice 2 weeks after surgery. LLLT treatment of Tsk(-/+) mice restored blood flow to levels observed in C57Bl/6 mice. Vascular density was decreased, angiostatin expression was enhanced and angiomotin depressed in the ischemic hindlimb of Tsk(-/+) mice. LLLT treatment reversed these abnormalities. LLLT stimulates angiogenesis by increasing angiomotin and decreasing angiostatin expression in the ischemic hindlimb of Tsk(-/+) mice.

Radiation exposure during percutaneous coronary interventions and coronary angiograms performed by the radial compared with the femoral route.

OBJECTIVES: This study aimed to compare radiation exposure of patients undergoing percutaneous coronary interventions (PCI) and coronary angiograms (CAG) accessed by the femoral route with the radial route (operator's choice). BACKGROUND: There are limited and contradictory data on the radiation exposure of patients during PCI and CAG performed by the radial route compared with the femoral route. METHODS: Data on the radiation exposure of patients from 3,973 PCI and CAG procedures between June 22, 2004, and December 31, 2008, were prospectively collected and analyzed. A prediction model was made for radiation exposure (dose-area product in Gy·cm(2)) based upon the femoral access group, and the group of radial performed procedures was compared to assess differences between observed and expected radiation exposure. RESULTS: Median exposures of patients undergoing a PCI via the femoral route (n = 2,309) was 75 (interquartile range [IQR]: 44 to 135) Gy·cm(2) compared with 72 (IQR: 42 to 134) Gy·cm(2) for radial performed procedures (n = 1,212) (p = 0.30). Median exposure for CAGs was 44 (IQR: 31 to 69) Gy·cm(2) and 40 (IQR: 25 to 65) Gy·cm(2) for, respectively, femoral (n = 314) and radial performed procedures (n = 138), (p = 0.31). Also, the observed radiation exposure in patients undergoing radial PCI or CAGs was not higher than the expected exposure of patients as predicted by the femoral access-based prediction model (71.5 ± 2.3 Gy·cm(2) vs. 79.9 ± 1.8 Gy·cm(2,)). CONCLUSIONS: The study shows that even after correction for the complexity of the procedures, selected procedures performed by the radial route are not associated with higher radiation exposure of patients than selected procedures performed by the femoral route.

Intimal sarcoma of the superficial femoral artery with osteosarcomatous differentiation.

Sarcomas of the large vessels usually present centrally in the aorta, pulmonary artery, and inferior vena cava. Peripheral arterial sarcomas are exceptionally rare. They have been reported in the iliac and common or profunda femoral arteries, and are frequently undifferentiated. In this study, we describe a differentiated intimal sarcoma of the superficial femoral artery with abundant osteosarcoma within the specimen. Before knowing the diagnosis, treatment was for a presumed pseudoaneurysm using excision and bypass. Postoperatively, the patient received palliative radiation therapy. The tumor's location and histopathology are unique. A differentiated intimal sarcoma has never been reported in the superficial femoral artery, and it represents the second peripheral arterial intimal sarcoma reported with osteosarcomatous differentiation.

Hemodynamic changes induced by preventive exposure to terahertz radiation at a frequency range corresponding to molecular emission and absorption spectrum of nitric oxide in animals under conditions of acute stress.

We studied the influence of preventive irradiation with terahertz electromagnetic waves at frequencies corresponding to nitric oxide emission and absorption molecular spectrum (150,176-150,664 GHz) on hemodynamic parameters in arteries of albino rats upon acute immobilization stress. We showed that exposure to the specified frequencies can produce adaptogenic effect manifesting in the absence of post-stress changes in the linear, systolic, and diastolic blood flow velocities and pressure gradient in various blood vessels of experimental animals.

[The impact of microbubbles-mediated intermitten HIFU on bloodflow in femoral artery of rabbit].

This study sought to find out whether the femoral artery of rabbit could be occluded after microbubbles mediated intermitten ultrasound exposure. One hundred and eight rabbits were randomly divided into 3 groups subjected to 3 different factors, namely ultrasound, HIFU combined with Microbubble (the intermitten mode and the continuous mode). After exposure, HE staining was used for visual inspection of the histopathologic change of femoral artery. Electron microscope was used for observation of the ultramicrostructural change; digital subtraction radiography (DSA) was used for inspections of the change in blood flow. There were thrombi formed in the femoral artery and the blood flow was occluded; the endarterium of the femoral artery of rabbits was damaged, and there was cavitation observed in the intermitten exposure group. In the other two groups, there was no change in the the femoral artery of rabbits. Thrombus could be formed in the femoral artery, and blood flow was occluded after exposure to microbubbles-mediated intermitten HIFU.

Irradiation inhibits vascular anastomotic stenosis in a canine model.

OBJECTIVE: The graft patency rate after coronary artery bypass grafting (CABG) correlates with anastomotic stenosis. Intracoronary radiation therapy is effective for preventing restenosis after percutaneous coronary intervention (PCI). We postulated that intracoronary radiation therapy could prevent anastomotic stenosis and tested this hypothesis in an animal model. METHODS: Femoral arteries and veins of beagle dogs were harvested, and composite arterioarterial and arteriovenous grafts were prepared. After external irradiation of the anastomotic sites, these composite grafts were transplanted into femoral arteries. Histomorphometric and immunohistological analyses of the anastomotic sites were performed. The study groups consisted of controls and animals exposed to 10 Gy, 20 Gy, and 30 Gy (n = 5, in each group). RESULTS: In the artery graft model, the ratio of negative remodeling was significantly increased in all groups exposed to >or=10 Gy. The ratio of neointimal hyperplasia was significantly decreased in all groups exposed to >or=10 Gy. Cell density of anti-alpha-actin antibody-positive cells and anti-proliferating cell nuclear antigen (PCNA) antibody-positive cells was highest in the adventitial layer, and the density decreased as the dosage increased. Experimental results were almost the same in the vein graft models as in the artery graft models. With double immunohistostaining, the anti-PCNA antibody-positive cells expressed alpha-actin. CONCLUSION: Irradiation can inhibit anastomotic stenosis in a canine model. Adventitia is a factor in the creation of stenosis, and irradiation appears to target the adventitia. We speculate that there might be a possible role for intracoronary irradiation in the future to prevent anastomotic stenosis.

[Spontaneous rupture of the femoral artery after radiotherapy: a case report]. / Rottura spontanea dell'arteria femorale dopo radioterapia: presentazione di un caso clinico.

Radiation-induced arteriopathy is a well-known disease whose incidence is not known and which usually arises chronically many years after radiation therapy. When it arises acutely, spontaneous rupture or, more rarely, thrombosis of the involved vessel may occur. Spontaneous rupture can occur within 4 to 32 weeks of radiotherapy, and usually affects the carotid artery involved in radiotherapy of the neck and head. Spontaneous rupture of the femoral artery is a very rare event and only a few cases have been reported in the literature. In this paper we report a case of spontaneous rupture of the left femoral superficial artery after adjuvant radiotherapy following surgery for a liposarcoma of the spermatic cord with multiple local recurrences, successfully treated with an extra-anatomic bypass through the obturator canal and rectal muscle flap.

Occlusive arterial disease after radiotherapy for testicular cancer: case report and review of the literature.

Radiation injury to arterial occlusion is a rare and late complication of radiotherapy. Numerous adverse reactions may occur secondary to radiation therapy. A well-known side effect is radiation-induced occlusive lesions and the enhancement of normally occurring atherosclerosis. We report a case of symptomatic right iliac and femoral artery occlusion after radiation therapy for carcinoma of the testis.

Radiation-induced peripheral artery disease.

Radiation therapy is a cause of cardiovascular morbidity and mortality. This is due to the significant degree of atherosclerosis seen in the vessels in the vicinity of the area being irradiated. Radiation-induced peripheral arterial disease is increasingly being recognized as large populations of cancer patients survive longer, yet it is a problem that is often under reported. Although it has most commonly been associated with carotid artery disease, all vascular beds are prone to this form of injury. The injury is accelerated by usual risk factors for atherosclerosis. Developing a healthy lifestyle, dietary prudence and the aggressive treatment of hypertension, diabetes mellitus, and dyslipidemia should all be encouraged in this patient population. When revascularization strategies are warranted, the percutaneous approach may be superior to open surgery as technical difficulties may arise in the fibrotic, scarred tissue. Stenting with distal embolic protection devices should be considered as the treatment of choice for patients with radiation-induced carotid artery disease. Several reports also suggest good results with balloon angioplasty with or without stenting in the case of radiation-induced renal, iliac, and femoral artery disease. Lifelong antiplatelet therapy may be appropriate.