Clinical evaluation of endovascular repair of abdominal aortic aneurysm based on long-term experiences.

INTRODUCTION: The endovascular method as a less invasive treatment for patients with abdominal aortic aneurysm (AAA) has become an alternative to conventional open surgery. AIM: The objective of the present study was to analyse the outcomes of endovascular treatment of AAA patients in long-term observation. MATERIAL AND METHODS: A group of 236 AAA patients subjected to planned endovascular aneurysm repair (EVAR) between 2010 and 2015 was reviewed. Rates of mortality, surgical complications and re-interventions were collected in the separate time periods, i.e. up to 30 days after surgery, 30 days to 3 years, and from 3 to 5 years after surgery. Cumulative rates of these parameters were evaluated in the short-term (up to 30 days after surgery), medium-term (up to 3 years), and long-term (up to 5 years after surgery) perspective. RESULTS: The median age of patients was 75 years, and the most common comorbidities were arterial hypertension (54%) and ischaemic heart disease (52%). Cumulative short-, medium- and long-term mortality rates were 2.5%, 14.2% and 28.9%, respectively. Total rates of surgical complications in short-, medium- and long-term observation were 7.6%, 12.6% and 17.5%, respectively. The cumulative rate of re-interventions ranged from 4.2% to 11.4%. CONCLUSIONS: In the consecutive time periods, the increase in the percentage of surgical complications and re-interventions increased gradually, in contrast to mortality, where the curve grew significantly, which is expected due to the aging and numerous comorbidities in the observed group of patients.

T Cells Are Dominant Population in Human Abdominal Aortic Aneurysms and Their Infiltration in the Perivascular Tissue Correlates With Disease Severity.

Abdominal Aortic Aneurysm (AAA) is a major cause of cardiovascular mortality. Adverse changes in vascular phenotype act in concert with chronic inflammation to promote AAA progression. Perivascular adipose tissue (PVAT) helps maintain vascular homeostasis but when inflamed and dysfunctional, can also promote vascular pathology. Previous studies suggested that PVAT may be an important site of vascular inflammation in AAA; however, a detailed assessment of leukocyte populations in human AAA, their anatomic location in the vessel wall and correlation to AAA size remain undefined. Accordingly, we performed in depth immunophenotyping of cells infiltrating the pathologically altered perivascular tissue (PVT) and vessel wall in AAA samples at the site of maximal dilatation (n = 51 patients). Flow cytometry revealed that T cells, rather than macrophages, are the major leukocyte subset in AAA and that their greatest accumulations occur in PVT. Both CD4+ and CD8+ T cell populations are highly activated in both compartments, with CD4+ T cells displaying the highest activation status within the AAA wall. Finally, we observed a positive relationship between T cell infiltration in PVT and AAA wall. Interestingly, only PVT T cell infiltration was strongly related to tertiles of AAA size. In summary, this study highlights an important role for PVT as a reservoir of T lymphocytes and potentially as a key site in modulating the underlying inflammation in AAA.

Treatment of high- and intermediate-risk pulmonary embolism using the AngioJet percutaneous mechanical thrombectomy system in patients with contraindications for thrombolytic treatment - a pilot study.

INTRODUCTION: Intravenous thrombolysis is the treatment of choice in patients presenting with high- and intermediate-risk pulmonary embolism. The role of percutaneous mechanical pulmonary thrombectomy (PMPT) is not fully established, although selected patients can be managed with this method. AIM: This open-label single-centre prospective pilot study was aimed at assessing the feasibility of PMPT for the treatment of severe pulmonary embolism in a Polish hospital. We also evaluated the safety and efficacy of such management. MATERIAL AND METHODS: We managed 7 patients, aged 52.7 ±16.6 years, presenting with high- and intermediate-risk pulmonary embolism (4 patients with class 5 and one patient with class 4 of the Pulmonary Embolism Severity Index), with occlusion of at least 2 lobar arteries and contraindications for thrombolysis. Percutaneous mechanical pulmonary thrombectomy was performed using the AngioJet system. RESULTS: It was possible to introduce the thrombectomy system to the pulmonary arteries in all patients. The procedure was successful in 6 patients (technical success rate: 85.7%). Two (28.6%) patients died during the hospital stay, one patient with unsuccessful thrombectomy and the other due to pneumonia. In all survivors control echocardiography demonstrated normalised function of the right ventricle. Also, dyspnoea disappeared and blood gas parameters normalised. There was no recurrent thromboembolism during 3-14 months of follow-up. CONCLUSIONS: In the Polish setting, in selected patients, management of high- and intermediate-risk pulmonary embolism with PMPT is technically feasible. Such treatment is relatively safe and effective. It can be an alternative to standard management, especially in patients with contraindications for fibrinolysis or surgical embolectomy.

Mechanisms of oxidative stress in human aortic aneurysms--association with clinical risk factors for atherosclerosis and disease severity.

UNLABELLED: Aortic abdominal aneurysms (AAA) are important causes of cardiovascular morbidity and mortality. Oxidative stress may link multiple mechanisms of AAA including vascular inflammation and increased metalloproteinase activity. However, the mechanisms of vascular free radical production remain unknown. Accordingly, we aimed to determine sources and molecular regulation of vascular superoxide (O2(-)) production in human AAA. METHODS AND RESULTS: AAA segments and matched non-dilated aortic samples were obtained from 40 subjects undergoing AAA repair. MDA levels (determined by HPLC/MS) were greater in plasma of AAA subjects (n=16) than in risk factor matched controls (n=16). Similarly, superoxide production, measured by lucigenin chemiluminescence and dihydroethidium fluorescence, was increased in aneurysmatic segments compared to non-dilated aortic specimens. NADPH oxidases and iNOS are the primary sources of O2(-) in AAA. Xanthine oxidase, mitochondrial oxidases and cyclooxygenase inhibition had minor or no effect. Protein kinase C inhibition had no effect on superoxide production in AAA. NADPH oxidase subunit mRNA levels for p22phox, nox2 and nox5 were significantly increased in AAAs while nox4 mRNA expression was lower. Superoxide production was higher in subjects with increased AAA repair risk Vanzetto score and was significantly associated with smoking, hypercholesterolemia and presence of CAD in AAA cohort. Basal superoxide production and NADPH oxidase activity were correlated to aneurysm size. CONCLUSIONS: Increased expression and activity of NADPH oxidases are important mechanisms underlying oxidative stress in human aortic abdominal aneurysm. Uncoupled iNOS may link oxidative stress to inflammation in AAA. Oxidative stress is related to aneurysm size and major clinical risk factors in AAA patients.

Local inflammation is associated with aortic thrombus formation in abdominal aortic aneurysms. Relationship to clinical risk factors.

Intraluminal thrombus formation in aortic abdominal aneurysms (AAA) is associated with adverse clinical prognosis. Interplay between coagulation and inflammation, characterised by leukocyte infiltration and cytokine production, has been implicated in AAA thrombus formation. We studied leukocyte (CD45+) content by flow cytometry in AAA thrombi from 27 patients undergoing surgical repair. Luminal parts of thrombi were leukocyte-rich, while abluminal segments showed low leukocyte content. CD66b+ granulocytes were the most prevalent, but their content was similar to blood. Monocytes (CD14+) and T cells (CD3+) were also abundant, while content of B lymphocytes (CD19+) and NK cells (CD56+CD16+) were low. Thrombi showed comparable content of CD14highCD16- monocytes and lower CD14highCD16+ and CD14dimCD16+, than blood. Monocytes were activated with high CD11b, CD11c and HLA-DR expression. Total T cell content was decreased in AAA thrombus compared to peripheral blood but CD8 and CD3+CD4-CD8- (double negative T cell) contents were increased in thrombi. CD4+ cells were lower but highly activated (high CD69, CD25 and HLA-DR). No differences in T regulatory (CD4+CD25+FoxP3+) cell or pro-atherogenic CD4+CD28null lymphocyte content were observed between thrombi and blood. Thrombus T cells expressed high levels of CCR5 receptor for chemokine RANTES, commonly released from activated platelets. Leukocyte or T cell content in thrombi was not correlated with aneurysm size. However, CD3+ content was significantly associated with smoking in multivariate analysis taking into account major risk factors for atherosclerosis. In conclusion, intraluminal AAA thrombi are highly inflamed, predominantly with granulocytes, CD14highCD16- monocytes and activated T lymphocytes. Smoking is associated with T cell infiltration in AAA intraluminal thrombi.

Mechanisms of increased vascular superoxide production in human varicose veins.

INTRODUCTION: Varicose vein disease is one of the most common morbidities in the developed countries. Recent studies have shown that oxidative stress is increased in varicose veins (VV) and venous insufficiency. However, the exact mechanisms of oxidative stress in VV remain unknown. OBJECTIVES: The aim of the study was to measure superoxide anion production and analyze its enzymatic sources in VV in comparison with control human saphenous veins (HSV). Superoxide production was also compared between the proximal and distal segments of the veins. PATIENTS AND METHODS: Proximal and distal segments of varicose veins (14 patients, aged 52 ±3.5 years) and control veins (15 patients, aged 56 ±4 years) were obtained during VV removal or elective coronary artery bypass graft surgery, respectively. Subjects were matched for age, sex, and the major risk factors for atherosclerosis. Superoxide was measured by lucigenin-enhanced chemiluminescence (5 µmol/l) in the presence and absence of oxidase inhibitors. RESULTS: Superoxide production was increased in VV compared with control HSV. This increase was particularly evident in the distal segments of VV. There was a significant correlation between superoxide production in the proximal and distal segments of HSV but not of VV. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and uncoupled nitric oxide synthase (NOS) were the major sources of superoxide in VV, because their inhibitors greatly attenuated superoxide production in VV. CONCLUSIONS: NADPH oxidases and NOS could represent valuable drug targets for pharmacological treatment and prevention of varicose vein disease. Oxidative stress may provide a link between endothelial dysfunction, inflammation, and immune activation and the development of chronic venous dysfunction.