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Aterosklerozė, kaip arterijas pažeidžianti liga, žinoma jau daugelį metų. Periferinių arterijų okliuzinės ligos (PAOL) simptomus jaučia apie 27 milijonai žmonių Šiaurės Amerikoje ir Europoje. Nežiūrint gerėjančios PAOL diagnostikos, chirurginio, endovaskulinio ir medikamentinio gydymo, jos paplitimas toliau didėja. Ši liga ypač neigiamai veikia gyvenimo kokybę ir išgyvenamumą. Populiacijai senstant, 2040 metais žmonių, sergančių PAOL, skaičius padidės iki 22 proc.. Taigi, akivaizdžiai galime pastebėti, kad žmonėms senstant, daugėja PAOL sergančiųjų ir ši liga progresuoja, blogina žmonių gyvenimo kokybę bei didina mirštamumą ar sunkina gretutinių susirgimų eigą. Ilgėjant žmonių amžiui, jie turi daug gretutinių susirgimų. Todėl PAOL operacinis gydymas gali būti gyvybei pavojingas, nes sukelia gretutinių ligų pasunkėjimą. Šiuo metu šią problemą bandoma spręsti pritaikant endovaskulinius arterijų užakimo koregavimo metodus, kurie yra mažai invazyvūs, atliekami vietinėje nejautroje ir sąlyginai pigūs. Darbo tikslas: palyginti subintiminės angioplastikos (SA), arterijų šuntavimo operacijų ir perkutaninės transliuminalinės angioplastikos (PTA) gydymo rezultatus, esant paviršinės šlaunies arterijos lėtiniam užakimui bei įvertinti subintiminės angioplastikos rizikos veiksnius. Darbo uždaviniai: 1. Įvertinti subintiminės ir perkutaninės transliuminalinės angioplastikų bei arterijų šuntavimo operacijos ypatumus, gydant lėtinį paviršinės šlaunies arterijos užakimą. 2. Įvertinti... [toliau žr. visą tekstą] / The Aim The aim of this study is to compare the results of subintimal angioplasty (SA), the bypass surgery and percutaneus transluminal angioplasty (PTA) in treatment of the chronic occlusion of superficial femoral artery (SFA) and determine risk factors of subintimal angioplasty. The objectives: 1. To evaluate peculiarity of subintimal and percutaneus transluminal angioplasty and arterial bypass surgery in treatment the chronic occlusion of superficial femoral artery. 2. To evaluate the primary results of subintimal and percutaneus transluminal angioplasty and arterial bypass surgery in treatment the chronic occlusion of superficial femoral artery. 3. To evaluate the early results of subintimal and percutaneus transluminal angioplasty and arterial bypass surgery in treatment the chronic occlusion of superficial femoral artery. 4. To determine risk factors predicting the primary and the early results of chronic superficial femoral artery occlusion treatment by means of subintimal and percutaneus transluminal angioplasty and the arterial bypass surgery. 2.1. Patients The prospective clinical study is being performed at the Department of Vascular Surgery of the Clinic of Cardiac, Thoracic and Vascular Surgery of Kaunas University of Medicine. The study was started in November 2002 and ended on December 2006. We had 255 patients admitted to the clinic during this period of time due to the occlusion of SFA, which matched the criteria of the study. The patients were... [to full text]

<p><h1>ABSTRACT</h1> <h1>Individuals with spinal cord injuries (SCI) are prone to significant alterations in vascular structure and function. This study was designed to examine the effects of osteopathic treatment on mean leg (MLBF) blood flow and skin temperature in the lower extremities of individuals with chronic SCI compared to able-bodied (AB) individuals. Methods: Nine individuals (age 44 ± 17.5 years) with a chronic SCI (C6-T12; AIS A-B; 3.7 ± 4.6 years post-injury) and six AB individuals (38.3 ± 9.7 years) participated. The protocol consisted of 1 interview session and 3 osteopathic treatment sessions. Doppler ultrasound measured the diameter and mean blood velocity in the CFA before (Pre) and after (Post) each session. Skin temperatures were measured using skin thermistors at three different sites on the left leg. Change scores were calculated and measured as post-treatment minus pre-treatment. Results: A two-way ANOVA revealed an increase in flow of 16±2 ml/min within the SCI group and a decrease in flow of 25±2 ml/min in the AB group (p = 0.04). There was also a smaller reduction in skin temperature in individuals within the SCI versus AB (left thigh: SCI, -0.5±0.2° C; AB, -1.2±0.2°C, p(left foot: SCI, -0.1±0.4°C; AB, -1.8±0.4°C, pAll treatments resulted in small increases in MLBF in the SCI group versus small decreases in the able-bodied group and smaller skin temperature decreases in the SCI versus the decreases in the AB group, potentially indicating reduced skin temperature reactivity. These findings emphasize the potential for different physiological responses to interventions in individuals with SCI compared to AB individuals.</h1></p> / Master of Science in Kinesiology

Peripheral artery disease (PAD) affects more than 200 million people worldwide. PAD refers to illness due to a reduction or complete occlusion of blood flow in the artery, especially to the extremities in disease conditions, such as atherosclerosis or diabetes. Critical limb ischemia (CLI) is a severe form of PAD associated with high morbidity and mortality. Currently, no effective and permanent treatments are available for this disease. The current endovascular medications (e.g., angioplasty or stents) only relieve the clinical symptoms while the surgical therapies (e.g., bypass or endarterectomy) require grafting vessels from a healthy organ to the diseased limb of the patient. However, even with these therapeutic techniques, 30% of patients still undergo limb amputation within a year. Thus, understanding of disease mechanism and development of new therapeutic approaches are in urgent needs. Meis1 (myeloid ecotropic viral integration site 1) gene belongs to the three-amino-acid loop extension subclass of homeobox gene families, and it is a highly conserved transcription factor in all eukaryotes. Up to date, little is known about the role of Meis1 in regulating vascular remodeling under ischemic condition. In this study, we aim to investigate the role and underlying mechanism of Meis1 in the regulation of arteriogenesis and angiogenesis using hindlimb ischemia model of transgenic neonatal mice. The long-term goal is to develop a new treatment for patients with PAD. Three separate but related studies were planned to complete the proposed research aims. To better understand the role of Meis1, we reviewed, in the first chapter, all literature relevant to the recent advances of the Meis1 in normal hematopoiesis, vasculogenesis, and heart developments, which were mostly studied in zebrafish and mouse. Briefly, Meis1 is found to be highly expressed in the brain and retina in zebrafish and additional in the heart, nose, and limb in mouse during the very early developmental stage, and remains at a low level quickly after birth. Meis1 is necessary for both primitive and definitive hematopoiesis and required for posterior erythroid differentiation. The absence of Meis1 results in a severe reduction of the number of mature erythrocytes and weakens the heart beats in zebrafish. Meis1 deficiency mouse is dead as early as E11.5 due to the severe internal hemorrhage. In addition, Meis1 is essential in heart development. Knock-down of Meis1 can promote angiotensin II-induced cardiomyocytes (CMs) hypertrophy or CMs proliferation, which can be repressed by a transcription factor Tbx20. Meis1 appears to play a complicated role in the blood vessels. Although the major blood vessels are still normal when global deletion of Meis1, the intersegmental vessel cannot be formed in Meis1 morphants in the zebrafish, and the small vessels are either too narrow or form larger sinuses in Meis1 deficient mouse. The effects of Meis1 on the vascular network under normal and disease (ischemia) condition remain largely unknown, and the existing data in this field is limited. In the second chapter, we developed a method protocol to identify mice of all ages, especially neonates that we faced methodological difficulties to easily and permanently label prior to our major experiments. In this study, single- or 2-color tattooing (ear, tail, or toe or combinations) was performed to identify a defined or unlimited number of mice, respectively. Tail tattooing using both green and red pastes was suitable for identifying white-haired neonatal mice as early as postnatal day (PND) 1, whereas toe tattooing with green paste was an effective alternative approach for labeling black-haired mouse pups. In comparison, single-color (green) or 2-color (green and red) ear tattooing identified both white and black adult mice older than three weeks. Ear tattooing can be adapted to labeling an unlimited number of adult mice by adding the cage number. Thus, tattooing various combinations of the ears, tail, and toes provides an easy and permanent approach for identifying mice of all ages with minimal disturbance to the animals, which shows a new approach than any existing method to identify mouse at all ages, especially the neonatal pups used in the present study (Chapter 4). Various formation of hindlimb ischemia with ligations of femoral artery or vein or both have been reported in the literature. The ischemic severity varies dependent on mouse strains and ligation methods. Due to the tiny body size of our experimental neonatal mice (PND2), it is technically challenging to separate the femoral artery from femoral vein without potential bleeding. In the third chapter, we aimed to explore a suitable surgical approach that can apply to neonatal mice. To this end, we compared the effects of femoral artery/vein (FAV) excision vs. femoral artery (FA) excision on hindlimb model using adult CD-1 mice. We showed during the 4-week period of blood reperfusion, no statistically significant differences were found between FAV and FA excision-induced ischemia regarding the reduction of limb blood flow, paw size, number of necrotic toes, or skeletal muscle cell size. We conclude that FAV and FA excision in CD-1 mice generate a comparable severity of hindlimb ischemia. In other words, FAV ligation is no more severe than FA ligation. These findings provide valuable information for researchers when selecting ligation methods for their neonate hindlimb models. Based on these findings, we selected FAV ligation of hindlimb ischemia approach to study the function of Meis1 in vascular remodeling of neonatal mice. In the fourth chapter (the main part of my dissertation), we investigated the roles of Meis1 in regulating arteriogenesis and angiogenesis of neonatal mouse under the ischemic condition. To this end, endothelial cell-specific deletion of Meis1 was generated by cross-breeding Meis1flox/flox mice with Tie2-Cre mice. Wild-type (WT, Meis1f/f) and endothelial cell-specific knock-out (KO, Meis1ec-/-Tie2-Cre+) C57BL/6 mice at the age of PND2 were used. Under the anesthesia, the pups were subject to hindlimb ischemia by excising FAV. Laser Doppler Imager was used to measure the blood flow pre- and post-surgery up to 28 days. Toe necrosis, skeletal regeneration, and vascular distributions were examined at the end of experiments (PND28 post-ischemia). Surprisingly, during 4-week periods after ischemia, the blood flow ratios (ischemic vs. control limb) in KO mice significantly increased compared to WT on PND14 and PND28, suggesting the inhibitory effects of Meis1 on blood flow recovery under ischemic condition. Meanwhile, WT mice showed more severe necrotic limb (lower ratio of limb length and area, and higher necrotic scores at PND7) than those in the KO mice. Furthermore, significant increases in diameters of Dil-stained arterioles of the skin vessel and the vessels on the ligation site were observed in KO mice, indicating the enhanced arteriogenesis in KO mice. To investigate the underlying mechanism, RNA from the ischemia and control limb was extracted and q-PCR was used to study the potential genes involved in the mechanism. Casp3 and Casp8 were found downregulated showing less apoptosis in the KO mice. On the other hand, endothelial cells (ECs) were isolated from the lungs of 3-5 WT and KO neonates using CD31 Microbeads. CD31+ cells were plated and treated with 0, 0.5, and 1μM doxorubicin for 24 hours and analyzed with various assays. Meis1-KO ECs demonstrated higher cell viability and formed a higher number of vascular tubes than those in WT ECs following 0.5μM Dox treatment, presenting the potential ability of angiogenesis in KO-ECs. Furthermore, the increased viability in KO ECs may be due to the decreased expression or activities of Casp8 and Casp3. In conclusion, my present studies have developed a new methodology to easily and permanently identify all mice at any ages. The insignificant differences between FAV and FA ligations suggest that a relative-easy surgical approach could be used to generate hindlimb ischemic model, which potentially reduces the cost, decreases the surgical time and prevents damage of femoral nerve from surgical tools. More importantly, by using transgenic mice, we found that Meis1-KO dramatically increased blood flow and protected the ischemic hindlimb through vascular remodeling. Obviously, the molecular and cellular mechanisms underlying the above beneficial effects appear complicated and likely to involve multiple cellular remodeling processes and molecular signaling pathways to enhance arteriogenesis and angiogenesis and/or reduce cellular apoptosis through Meis1-mediated pathways. Our study demonstrated that under ischemic condition, knockout of Meis1 increases expression of Hif1a, which then activates Agt or VEGF, thus enhances arteriogenesis or angiogenesis; In addition, knockout of Meis1 activates Ccnd1, which subsequently promotes regeneration of skeletal muscle, and reduces expression of Casp8 and Casp3, thus preventing limb tissue from ischemia-induced apoptosis. Our innovative findings offer great potential to ultimately lead to new drug discovery or therapeutic approaches for prevention or treatment of PAD. / PHD / Peripheral artery disease (PAD), which affects more than 200 million people worldwide, commonly refers to the vascular diseases of legs or feet due to a reduction or even complete occlusion of blood flow to these areas. PAD is usually caused by blockage of main vessels in limbs under certain diseases, such as atherosclerosis. Unfortunately, no effective and permanent treatments are available for this disease. The current medications only relieve the clinical symptoms while the surgical therapy requires grafting vessels from a healthy organ to the diseased limb of the patient. In the present study, we aim to explore a new approach to facilitate the vessel formation in ischemic limb using Meis 1 transgenic mice. Meis 1 (myeloid ecotropic viral integration site 1) gene belongs to homeobox gene families, and it is a highly conserved transcription factor in all eukaryotes. My dissertation aims to understand how Meis 1 affects vascular remodeling in the mouse following induced hindlimb ischemia (to mimic PAD). To better understand the role of Meis 1, we first reviewed the literature studying the Meis 1 function on normal hematopoiesis, vasculogenesis, and heart development in zebrafish and mouse. The studies show that Meis 1 plays a complicated role in the blood vessels. When entirely deleting Meis 1 in the zebrafish, the intersegmental vessels cannot be formed. While in a mammal study, it is found that the major blood vessels are normal while the small vessels are either too narrow or form larger sinuses in Meis 1 deficient mouse. Thus, Mesi1 appears to play an important role in regulating vascular network, but the available information in this field is insufficient. The present projects aimed to study the roles of Meis 1 in regulating vascular remodeling following the hindlimb ischemia induced by ligation of main limb vessels (to mimic PAD). The transgenic mice with the deletion of Meis 1 (called knockout or KO mice) were generated by a Cre-loxP system (a gene manipulation method) to remove Meis 1 only in endothelial cells. The resulting KO mice were subject to the hindlimb ischemia and compared to those mice with the intact Meis 1 (called wild-type, or WT). To this end, the entire experiments contain three separate studies. In the first studies (Chapter 2), we developed an easy, but a permanent method to identify the mice at all age, especially the neonatal mice we used in the projects. Briefly, we used single- or 2-color tattooing to identify a defined or unlimited number of mice, respectively. We labeled our adult mice with ear tattooing combined with cage number and neonatal mice with toe tattooing if necessary to identify the individual animals. Next (Chapter 3), we determined the effects of femoral artery/vein (FAV) ligation vs. femoral artery (FA) ligation alone on hindlimb severities. The purpose of this study was to generate a suitable ligation model for the neonatal mice. Interestingly, no statistically significant differences were found between FAV and FA excision-induced ischemia, suggesting that FAV ligation could be applied to the neonatal hindlimb ischemia model in the rest of study. Upon the establishment of identification and ligation approaches for neonatal mice, we conducted systemic studies at both in vitro and in vivo settings to investigate the biological function of Meis 1 under ischemic condition. Briefly, two groups of Meis 1 mice at ages of postnatal day 2 were used in the study: WT (the normal mice), and endothelial specific knock-out (KO, Meis 1 gene was entirely deleted in endothelial cells). Under anesthesia, the postnatal day 2 pups were induced hindlimb ischemia, and blood flow was measured pre- and post-ischemia up to 4 weeks. Our data demonstrated that the blood flow was significantly higher in KO mice than WT mice, suggesting deletion of Meis 1 in endothelial cells can increase blood perfusion following ischemic injury. Moreover, the KO mice showed less toe damage compared with WT, thus showing protective benefit in rescuing the damaged limb. We also found that deletion of Meis 1 in endothelial cells increased cell viability and induced generation of more numbers of vessels under an induced apoptosis condition. These findings suggested that the deletion of Meis 1 in endothelial cells facilitates vessel formation and prevents the injured limbs from loss or undergoing apoptosis/necrosis, which may lead new drug discovery and development of effective therapy for treatments of PAD.

INTRODUÇÃO: A implantação de stent auto-expansível de nitinol para o tratamento das lesões oclusivas femoro-poplíteas tem sido associado com maus resultados a longo prazo. O everolimus administrado via oral para inibir reestenoses do stent foi investigado recentemente em animais com bons resultados, porém sua segurança e eficácia não têm sido estudada em seres humanos. O propósito deste estudo piloto foi avaliar o impacto da terapia antiproliferativa com everolimus administrado via oral por 28 dias na diminuição de reestenose após implante de stent auto-expansível de nitinol para tratamento de lesões oclusivas da artéria femoral superficial. MÉTODOS E RESULTADOS: Trinta e quatro pacientes foram recrutados para este estudo randomizado, prospectivo. O grupo que recebeu everolimus via oral foi constituído por 15 pacientes e o grupo que não recebeu medicação composto por 19 pacientes. As características basais e do procedimento foram similares entre os dois grupos. Todos os pacientes tinham isquemia crônica do membro inferior e oclusão da artéria femoral superficial (média da lesão de 83,14 mm no grupo sem medicação e 105 mm no grupo everolimus). O objetivo primário do estudo foi a redução da porcentagem média do diâmetro da reestenose intra-stent após seis meses da angioplastia avaliada por angiografia quantitativa. A porcentagem média do diâmetro das reestenoses foi 46,9% no grupo tratado com everolimus e 44,5% no grupo que não recebeu a medicação (p=0,81). Não foram observados efeitos colaterais graves nos grupos. No acompanhamento clínico aos 24 meses não houve diferenças significativas entre os grupos em relação a eventos clínicos. A patência primária, primária assistida e secundária em 24 meses, foi 42%, 74% e 79% no grupo sem medicação e 27%, 73% e 73% no grupo tratado com everolimus. CONCLUSÃO: O everolimus via oral por 28 dias em doses altas é seguro e bem tolerado, com baixo índice de efeitos colaterais, porém não é eficaz na redução da porcentagem média do diâmetro da reestenose intra-stent em pacientes com implante de stents auto-expansíveis de nitinol nas lesões oclusivas complexas da artéria femoral superficial. / INTRODUCTION: The implantation of a self-expanding of nitinol stent in the treatment of femoropopliteal occlusive lesions has been associated with a poor outcome in a long term setting. Everolimus administered orally to inhibit restenosis of the stent was investigated recently in animals with good results, but its safety and efficacy has not been studied in humans. The purpose of this pilot study was to evaluate the impact of antiproliferative therapy with everolimus administered orally for 28 days in the reduction of restenosis after implantation of self-expandable nitinol stent for treatment of occlusive lesions of the superficial femoral artery. METHODS AND RESULTS: Thirty-four patients were recruited for this randomized, prospective study. The group that received oral Everolimus was consisted of 15 patients and the group that received no medication was 19 patients. The baseline characteristics and procedure were similar in both groups. All the patients had chronic lower limb ischemia and occlusion of the superficial femoral artery (mean of the lesion of 83.14 mm in the group without medication and 105 mm in the everolimus group). The primary objective of the study was to evaluate the reduction of the average percentage of the diameter of in-stent restenosis six months after angioplasty assessed by quantitative angiography. The in-stent mean percent diameter stenosis was 46.9% in the group treated with everolimus and 44.5% in the group that received no medication (p = 0.81). There were no serious side effects seen in either group in the clinical follow up at 24 months. There was no significant difference between groups in relation to clinical events. The primary patency, assisted primary and secondary in 24 months was 42%, 74% and 79% in the group without medication and 27%, 73% and 73% in the group treated with Everolimus. CONCLUSION: Everolimus administered orally for 28 consecutive days to stent implantation in high doses proves to be safe and well tolerated, with low rate of side effects, but it is not effective in reducing the average percentage of diameter of in-stent restenosis in patients with implantation of self-expandable nitinol stent in complex occlusive lesions of the superficial femoral artery.

A via de acesso arterial é um importante sítio de complicações após a realização de procedimentos coronários invasivos. Dentre as estratégias para a redução de complicações vasculares, encontra-se estabelecida a eficácia da técnica radial. Os dispositivos de oclusão vascular propiciam maior conforto ao paciente, reduzindo o tempo de hemostasia e repouso no leito. Entretanto, a inconsistência de dados comprovando sua segurança limita sua adoção rotineira como estratégia para redução de complicações vasculares, requerendo evidências de estudos randomizados com metodologia adequada. O objetivo deste estudo foi comparar a incidência de complicações no sítio de punção arterial entre a técnica radial e a técnica femoral com utilização de Angio-Seal em pacientes com síndrome coronariana aguda sem supradesnível do segmento ST submetidos à estratégia invasiva precoce. Trata-se de um ensaio clínico unicêntrico, de não inferioridade, no qual duzentos e quarenta pacientes foram randomizados para a técnica radial ou técnica femoral com utilização de Angio-Seal. O objetivo primário foi a ocorrência de complicações no sítio de punção arterial até 30 dias após o procedimento, incluindo sangramento grave, hematoma >= 5 cm, hematoma retroperitoneal, síndrome compartimental, pseudoaneurisma, fístula arteriovenosa, infecção, isquemia de membro, oclusão arterial, lesão de nervo adjacente ou necessidade de reparo vascular cirúrgico. Em relação às características demográficas e clínicas, houve diferença apenas quanto ao gênero, com presença maior de pacientes do sexo feminino no grupo radial (33,3% versus 20,0%, p=0,020). Não se observaram diferenças entre os grupos quanto ao diagnóstico de admissão, alterações isquêmicas presentes no eletrocardiograma, elevação de marcadores de necrose miocárdica ou escores de risco, bem como quanto à farmacoterapia antitrombótica adjunta e características da intervenção coronária percutânea. A hemostasia foi obtida na totalidade dos procedimentos do grupo radial com a utilização da pulseira compressora seletiva TR Band e em 95% dos procedimentos realizados pela técnica femoral com o Angio-Seal (p=0,029). Exceto pela maior incidência de oclusão arterial no grupo radial comparado ao femoral, não houve diferenças entre os demais desfechos analisados. Segundo o teste de não inferioridade para complicações na via de acesso arterial aos 30 dias, verificou-se que a utilização do Angio-Seal não produziu resultados inferiores ao acesso radial, considerando-se a margem de 15% (12,5% versus 13,3%, diferença -0,83%, IC 95% -9,31 - 7,65, p para não inferioridade <0,001). Os resultados principais deste estudo demonstram que, em uma população de pacientes com diagnóstico de síndrome coronariana aguda sem supradesnível do segmento ST, submetida à estratificação de risco invasiva, a utilização do dispositivo de oclusão vascular Angio-Seal confere ao procedimento efetivado pelo acesso femoral inferioridade na incidência de complicações no sítio de punção arterial aos 30 dias quando comparado ao acesso radial. / Arterial access is a major site of complications after invasive coronary procedures. Among strategies to decrease vascular complications, the radial approach is an established one. Vascular closure devices provide more comfort to patients decreasing hemostasis and need for bed rest. However, the inconsistency of data proving their safety limits their routine adoption as a strategy to prevent vascular complications, requiring evidence through adequately designed randomized trials. The aim of this study is to compare the radial versus femoral approach using Angio-Seal for the incidence of arterial puncture site complications among non-ST-segment elevation acute coronary syndrome patients submitted to an early invasive strategy. This study is a unicentric, non-inferiority clinical trial where two hundred and forty patients with non-ST-segment elevation acute coronary syndrome were randomized to either radial or femoral access using Angio-Seal. The primary outcome was the occurrence of complications at the arterial puncture site until 30 days after the procedure, including major bleeding, hematoma >= 5 cm, retroperitoneal hematoma, compartment syndrome, pseudoaneurysm, arteriovenous fistula, infection, limb ischemia, arterial occlusion, adjacent nerve injury or the need for vascular surgery repair. With respect to demographic and clinical characteristics, there were differences only in terms of gender, with greater presence of female patients in the radial group (33.3% versus 20.0%, p = 0.020). There were no differences between the groups regarding the diagnosis of admission, ischemic changes present in the electrocardiogram, elevation of myocardial necrosis markers or risk scores, as well as the adjunct antithrombotic pharmacotherapy and features of the percutaneous coronary intervention. Hemostasis was achieved in the entire radial group with the use of selective radial compressor TR Band and in 95% of the procedures performed by femoral technique with Angio-Seal (p = 0.029). Except for a higher incidence of arterial occlusion in the radial group compared to the femoral, there were no differences among the other outcomes analyzed. According to the non-inferiority test for arterial access site complications in 30 days, it was found that the use of Angio-Seal not produced results inferior to the radial approach, considering the margin of 15% (12.5% vs. 13.3%, difference -0.83%, 95% CI -9.31 - 7.65, p for noninferiority <0.001). The main results of this study demonstrated that in a population of patients diagnosed with non-ST segment elevation acute coronary syndrome, who underwent invasive risk stratification, the use of the Angio-Seal vascular closure device confers to the femoral approach noninferiority in the incidence of arterial puncture site complications at 30 days when compared to the radial approach.

The mechanical behavior of the arterial wall is determined by the composition and structure of its internal constituents as well as the applied traction-forces, such as pressure and axial stretch. The purpose of this work is to develop new theoretical frameworks and experimental methodologies to further the understanding of arterial mechanics and role of the various intrinsic and extrinsic mechanically motivating factors. Specifically, residual deformation, matrix organization, and perivascular support are investigated in the context of their effects on the overall and local mechanical behavior of the artery. We propose new kinematic frameworks to determine the displacement field due to residual deformations previously unknown, which include longitudinal and shearing residual deformations. This allows for improved predictions of the local, intramural stresses of the artery. We found distinct microstructural differences between the femoral and carotid arteries from non-human primates. These arteries are functionally and mechanically different, but are geometrically and compositionally similar, thereby suggesting differences in their microstructural alignments, particularly of their collagen fibers. Finally, we quantified the mechanical constraint of perivascular support on the coronary artery by mechanically testing the artery in-situ before and after surgical exposure.

INTRODUÇÃO: A implantação de stent auto-expansível de nitinol para o tratamento das lesões oclusivas femoro-poplíteas tem sido associado com maus resultados a longo prazo. O everolimus administrado via oral para inibir reestenoses do stent foi investigado recentemente em animais com bons resultados, porém sua segurança e eficácia não têm sido estudada em seres humanos. O propósito deste estudo piloto foi avaliar o impacto da terapia antiproliferativa com everolimus administrado via oral por 28 dias na diminuição de reestenose após implante de stent auto-expansível de nitinol para tratamento de lesões oclusivas da artéria femoral superficial. MÉTODOS E RESULTADOS: Trinta e quatro pacientes foram recrutados para este estudo randomizado, prospectivo. O grupo que recebeu everolimus via oral foi constituído por 15 pacientes e o grupo que não recebeu medicação composto por 19 pacientes. As características basais e do procedimento foram similares entre os dois grupos. Todos os pacientes tinham isquemia crônica do membro inferior e oclusão da artéria femoral superficial (média da lesão de 83,14 mm no grupo sem medicação e 105 mm no grupo everolimus). O objetivo primário do estudo foi a redução da porcentagem média do diâmetro da reestenose intra-stent após seis meses da angioplastia avaliada por angiografia quantitativa. A porcentagem média do diâmetro das reestenoses foi 46,9% no grupo tratado com everolimus e 44,5% no grupo que não recebeu a medicação (p=0,81). Não foram observados efeitos colaterais graves nos grupos. No acompanhamento clínico aos 24 meses não houve diferenças significativas entre os grupos em relação a eventos clínicos. A patência primária, primária assistida e secundária em 24 meses, foi 42%, 74% e 79% no grupo sem medicação e 27%, 73% e 73% no grupo tratado com everolimus. CONCLUSÃO: O everolimus via oral por 28 dias em doses altas é seguro e bem tolerado, com baixo índice de efeitos colaterais, porém não é eficaz na redução da porcentagem média do diâmetro da reestenose intra-stent em pacientes com implante de stents auto-expansíveis de nitinol nas lesões oclusivas complexas da artéria femoral superficial. / INTRODUCTION: The implantation of a self-expanding of nitinol stent in the treatment of femoropopliteal occlusive lesions has been associated with a poor outcome in a long term setting. Everolimus administered orally to inhibit restenosis of the stent was investigated recently in animals with good results, but its safety and efficacy has not been studied in humans. The purpose of this pilot study was to evaluate the impact of antiproliferative therapy with everolimus administered orally for 28 days in the reduction of restenosis after implantation of self-expandable nitinol stent for treatment of occlusive lesions of the superficial femoral artery. METHODS AND RESULTS: Thirty-four patients were recruited for this randomized, prospective study. The group that received oral Everolimus was consisted of 15 patients and the group that received no medication was 19 patients. The baseline characteristics and procedure were similar in both groups. All the patients had chronic lower limb ischemia and occlusion of the superficial femoral artery (mean of the lesion of 83.14 mm in the group without medication and 105 mm in the everolimus group). The primary objective of the study was to evaluate the reduction of the average percentage of the diameter of in-stent restenosis six months after angioplasty assessed by quantitative angiography. The in-stent mean percent diameter stenosis was 46.9% in the group treated with everolimus and 44.5% in the group that received no medication (p = 0.81). There were no serious side effects seen in either group in the clinical follow up at 24 months. There was no significant difference between groups in relation to clinical events. The primary patency, assisted primary and secondary in 24 months was 42%, 74% and 79% in the group without medication and 27%, 73% and 73% in the group treated with Everolimus. CONCLUSION: Everolimus administered orally for 28 consecutive days to stent implantation in high doses proves to be safe and well tolerated, with low rate of side effects, but it is not effective in reducing the average percentage of diameter of in-stent restenosis in patients with implantation of self-expandable nitinol stent in complex occlusive lesions of the superficial femoral artery.

A via de acesso arterial é um importante sítio de complicações após a realização de procedimentos coronários invasivos. Dentre as estratégias para a redução de complicações vasculares, encontra-se estabelecida a eficácia da técnica radial. Os dispositivos de oclusão vascular propiciam maior conforto ao paciente, reduzindo o tempo de hemostasia e repouso no leito. Entretanto, a inconsistência de dados comprovando sua segurança limita sua adoção rotineira como estratégia para redução de complicações vasculares, requerendo evidências de estudos randomizados com metodologia adequada. O objetivo deste estudo foi comparar a incidência de complicações no sítio de punção arterial entre a técnica radial e a técnica femoral com utilização de Angio-Seal em pacientes com síndrome coronariana aguda sem supradesnível do segmento ST submetidos à estratégia invasiva precoce. Trata-se de um ensaio clínico unicêntrico, de não inferioridade, no qual duzentos e quarenta pacientes foram randomizados para a técnica radial ou técnica femoral com utilização de Angio-Seal. O objetivo primário foi a ocorrência de complicações no sítio de punção arterial até 30 dias após o procedimento, incluindo sangramento grave, hematoma >= 5 cm, hematoma retroperitoneal, síndrome compartimental, pseudoaneurisma, fístula arteriovenosa, infecção, isquemia de membro, oclusão arterial, lesão de nervo adjacente ou necessidade de reparo vascular cirúrgico. Em relação às características demográficas e clínicas, houve diferença apenas quanto ao gênero, com presença maior de pacientes do sexo feminino no grupo radial (33,3% versus 20,0%, p=0,020). Não se observaram diferenças entre os grupos quanto ao diagnóstico de admissão, alterações isquêmicas presentes no eletrocardiograma, elevação de marcadores de necrose miocárdica ou escores de risco, bem como quanto à farmacoterapia antitrombótica adjunta e características da intervenção coronária percutânea. A hemostasia foi obtida na totalidade dos procedimentos do grupo radial com a utilização da pulseira compressora seletiva TR Band e em 95% dos procedimentos realizados pela técnica femoral com o Angio-Seal (p=0,029). Exceto pela maior incidência de oclusão arterial no grupo radial comparado ao femoral, não houve diferenças entre os demais desfechos analisados. Segundo o teste de não inferioridade para complicações na via de acesso arterial aos 30 dias, verificou-se que a utilização do Angio-Seal não produziu resultados inferiores ao acesso radial, considerando-se a margem de 15% (12,5% versus 13,3%, diferença -0,83%, IC 95% -9,31 - 7,65, p para não inferioridade <0,001). Os resultados principais deste estudo demonstram que, em uma população de pacientes com diagnóstico de síndrome coronariana aguda sem supradesnível do segmento ST, submetida à estratificação de risco invasiva, a utilização do dispositivo de oclusão vascular Angio-Seal confere ao procedimento efetivado pelo acesso femoral inferioridade na incidência de complicações no sítio de punção arterial aos 30 dias quando comparado ao acesso radial. / Arterial access is a major site of complications after invasive coronary procedures. Among strategies to decrease vascular complications, the radial approach is an established one. Vascular closure devices provide more comfort to patients decreasing hemostasis and need for bed rest. However, the inconsistency of data proving their safety limits their routine adoption as a strategy to prevent vascular complications, requiring evidence through adequately designed randomized trials. The aim of this study is to compare the radial versus femoral approach using Angio-Seal for the incidence of arterial puncture site complications among non-ST-segment elevation acute coronary syndrome patients submitted to an early invasive strategy. This study is a unicentric, non-inferiority clinical trial where two hundred and forty patients with non-ST-segment elevation acute coronary syndrome were randomized to either radial or femoral access using Angio-Seal. The primary outcome was the occurrence of complications at the arterial puncture site until 30 days after the procedure, including major bleeding, hematoma >= 5 cm, retroperitoneal hematoma, compartment syndrome, pseudoaneurysm, arteriovenous fistula, infection, limb ischemia, arterial occlusion, adjacent nerve injury or the need for vascular surgery repair. With respect to demographic and clinical characteristics, there were differences only in terms of gender, with greater presence of female patients in the radial group (33.3% versus 20.0%, p = 0.020). There were no differences between the groups regarding the diagnosis of admission, ischemic changes present in the electrocardiogram, elevation of myocardial necrosis markers or risk scores, as well as the adjunct antithrombotic pharmacotherapy and features of the percutaneous coronary intervention. Hemostasis was achieved in the entire radial group with the use of selective radial compressor TR Band and in 95% of the procedures performed by femoral technique with Angio-Seal (p = 0.029). Except for a higher incidence of arterial occlusion in the radial group compared to the femoral, there were no differences among the other outcomes analyzed. According to the non-inferiority test for arterial access site complications in 30 days, it was found that the use of Angio-Seal not produced results inferior to the radial approach, considering the margin of 15% (12.5% vs. 13.3%, difference -0.83%, 95% CI -9.31 - 7.65, p for noninferiority <0.001). The main results of this study demonstrated that in a population of patients diagnosed with non-ST segment elevation acute coronary syndrome, who underwent invasive risk stratification, the use of the Angio-Seal vascular closure device confers to the femoral approach noninferiority in the incidence of arterial puncture site complications at 30 days when compared to the radial approach.