Smooth muscle cells of injured rat and rabbit arteries in culture: contractile and cytoskeletal proteins

The aim of this study is to determine whether subpopulations of smooth muscle cells (SMC). as distinguished by variations in contractile and cytoskeletal proteins, appear in the neointima at different times after vascular injury, and/or whether subpopulations develop during serial passaging of these cells. Rat aortae and rabbit carotid arteries were injured with a 2F Fogarty balloon catheter and cultures established from the resulting neointima and the media 2, 6, 12, 16 and 24 weeks later. Cultures were examined at passages 1-5 and subpopulations of SMC categorised by intensity of staining for each protein by immunohistochemistry. Two populations of SMC with different staining intensities ('+ +', '+') were observed for each of the following proteins: alpha -SM actin, SM-myosin, desmin and vimentin. Populations without these proteins were also found. Changes in the percentages of cells expressing these proteins were transitory, indicating that the populations were not limited to a particular tissue (neointima or media), time after injury or passage number. One exception was found in rabbit cultures where the number of desmin-expressing cells quickly decreased with both time after injury and time in culture. Subpopulations of SMC were found at all times after injury in the media and neointima of rat and rabbit arteries, and after multiple passage of these cells. There was no pattern of development of one population suggesting that either no subpopulation has a proliferative or migratory advantage over others, or that only one population exists: that is capable of diverse phenotypic changes. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Relationship of glycosaminoglycan and matrix changes to vascular smooth cell phenotype modulation in rabbit arteries after acute injury

Purpose: The phenotype of vascular smooth muscle cells (SMCs) is altered in several arterial pathologies, including the neointima formed after acute arterial injury. This study examined the time course of this phenotypic change in relation to changes in the amount and distribution of matrix glycosaminoglycans. Methods: The immunochemical staining of heparan sulphates (HS) and chondroitin sulphates (CS) in the extracellular matrix of the arterial wall was examined at early points after balloon catheter injury of the rabbit carotid artery. SMC phenotype was assessed by means of ultrastructural morphometry of the cytoplasmic volume fraction of myofilaments. The proportions of cell and matrix components in the media were analyzed with similar morphometric techniques. Results: HS and CS were shown in close association with SMCs of the uninjured arterial media as well as being more widespread within the matrix. Within 6 hours after arterial injury, there was loss of the regular pericellular distribution of both HS and CS, which was associated with a significant expansion in the extracellular space. This preceded the change in ultrastructural phenotype of the SMCs. The glycosaminoglycan loss was most exaggerated at 4 days, after which time the HS and CS reappeared around the medial SMCs. SMCs of the recovering media were able to rapidly replace their glycosaminoglycans, whereas SMCs of the developing neointima failed to produce HS as readily as they produced CS. Conclusions: These studies indicate that changes in glycosaminoglycans of the extracellular matrix precede changes in SMC phenotype after acute arterial injury. In the recovering arterial media, SMCs replace their matrix glycosaminoglycans rapidly, whereas the newly established neointima fails to produce similar amounts of heparan sulphates.

Regulation of LIF receptor expression in vascular smooth muscle

Previous studies in our laboratory have shown that the pleiotropic cytokine leukemia inhibitory factor (LIF) inhibits neointimal formation and the development and progression of atherosclerotic and restenotic lesions in a rabbit model of disease. The present study demonstrates an upregulation of both the LIF receptor (LIFR)-α subunit and the signal transducing subunit gp130 following endothelial denudation of the carotid artery by balloon catheter. Continuous infusion of LIF (30 μg/kg/day) resulted in the downregulation of LIFR-a in injured arteries in vivo. Similarly, smooth muscle cells in vitro treated with LIF exhibited a time-dependent reduction in LIFR-a protein expression and the subsequent reduction in transcription of the TIMP-1 gene. However, in the presence of an intact endothelium, LIFR-a was upregulated in response to LIF, and accordingly the downstream induction of iNOS expression was also increased. Thus, LIF exerts more potent antiatherogenic effects in the vasculature when the endothelium is intact.

Repeated three-dimensional magnetic resonance imaging of atherosclerosis development in innominate arteries of low-density lipoprotein receptor-knockout mice

Background-In vivo methods to evaluate the size and composition of atherosclerotic lesions in animal models of atherosclerosis would assist in the testing of antiatherosclerotic drugs. We have developed an MRI method of detecting atherosclerotic plaque in the major vessels at the base of the heart in low-density lipoprotein (LDL) receptor-knockout (LDLR-/-) mice on a high-fat diet. Methods and Results-Three-dimensional fast spin-echo magnetic resonance images were acquired at 7 T by use of cardiac and respiratory triggering, with approximate to140-mum isotropic resolution, over 30 minutes. Comparison of normal and fat-suppressed images from female LDLR-/- mice I week before and 8 and 12 weeks after the transfer to a high-fat diet allowed visualization and quantification of plaque development in the innominate artery in vivo. Plaque mean cross-sectional area was significantly greater at week 12 in the LDLR-/- mice (0.14+/-0.086 mm(2) [mean+/-SD]) than in wild-type control mice on a normal diet (0.017+/-0.031 mm(2), p

Use of an accelerated chest pain assessment protocol in patients at intermediate risk of adverse cardiac events

Objective: To determine the feasibility, safety and effectiveness of a structured clinical pathway for stratification and management of patients presenting with chest pain and classified as having intermediate risk of adverse cardiac outcomes in the subsequent six months. Design: Prospective clinical audit. Participants and setting: 630 consecutive patients who presented to the emergency department of a metropolitan tertiary care hospital between January 2000 and June 2001 with chest pain and intermediate-risk features. Intervention: Use of the Accelerated Chest Pain Assessment Protocol (ACPAP), as advocated by the Management of unstable angina guidelines - 2000 from the National Heart Foundation and the Cardiac Society of Australia and New Zealand. Main outcome measure: Adverse cardiac events during six-month follow-up. Results: 409 patients (65%) were reclassified as low risk and discharged at a mean of 14 hours after assessment in the chest pain unit. None had missed myocardial infarctions, while three (1%) had cardiac events at six months (all elective revascularisation procedures, with no readmissions with acute coronary syndromes). Another 110 patients (17%) were reclassified as high risk, and 21 (19%) of these had cardiac events (mainly revascularisations) by six months. Patients who were unable to exercise or had non-diagnostic exercise stress test results (equivocal risk) had an intermediate cardiac event rate (8%). Conclusions: This study validates use of ACPAP. The protocol eliminated missed myocardial infarction; allowed early, safe discharge of low-risk patients; and led to early identification and management of high-risk patients.

Avaliação funcional e farmacológica do corpo carotídeo do rato no envelhecimento

Resumo: O corpo carotídeo gera o quimiorreflexo à hipoxia, tendo por objectivo principal a homeostase dos gases do sangue. Esta tese testou a hipótese da função destes quimiossensores não se deteriorar ao longo da idade. In vivo, em ratos anestesiados, foram estudados os efeitos da idade nas respostas cardiorespiratórias a dois tipos de estímulos diferentes: a isquemia carotídea e a manipulação farmacológica de dois neurotransmissores com efeitos opostos nos quimiorreceptores, a adenosina e a dopamina. O modelo de isquemia carotídea corresponde à oclusão bilateral da artéria carótida comum, durante períodos de 5 a 15 s, o que determina um efeito excitatório na ventilação que é abolido pela secção bilateral dos nervos do seio carotídeo. No estudo farmacológico foram analisadas as respostas cardio-respiratórias à adenosina e à dopamina exógenas na presença e na ausência de antagonistas selectivos para os receptores A2A e D2, respectivamente. In vitro, no corpo carotídeo, foi quantificado o efeito de diferentes concentrações de oxigénio no conteúdo do segundo mensageiro comum à activação dos receptores A2A e D2, o cAMP. Em conjunto, estes resultados demonstraram que no rato o controlo da ventilação pelo corpo carotídeo se mantém inalterado ao longo da idade.--------------------- ABSTRACT: The carotid body initiates reflexes aimed principally at the homeostatic maintenance of blood gas tensions. This thesis tested the hypothesis of the function of these quimiossensores not deteriorate through age. In vivo, in anesthetized rats, we studied the effects of age on cardiorespiratory responses to two different types of stimuli: carotid ischemia and pharmacological manipulation of neurotransmitters with two opposite effects on chemoreceptors, adenosine and dopamine. The model of carotid ischemia corresponded to bilateral occlusion of common carotid artery, during periods of 5 to 15 s, which determines an excitatory effect on ventilation that is abolished by bilateral section of carotid sinus nerve. The pharmacological study analyzed the cardiorespiratory responses to exogenous adenosine and dopamine in the presence and absence of selective antagonists for the A2A and D2 receptors, respectively. In vitro, at the carotid body, it was quantified the effect of different concentrations of oxygen in the content of the common second messenger for the activation of A2A and D2 receptors, the cAMP. Together, these results showed that in rats the control of ventilation by carotid body remains unchanged through age.

Embolização das artérias prostáticas no tratamento da hiperplasia benigna da próstata : estudo anátomo-clínico

Resumo: A hiperplasia benigna da próstata (HBP) tem elevada prevalência nos homens entre os 50 e 79 anos de idade, sendo ubiquitária com o envelhecimento. Devido à significativa morbi-mortalidade associada aos tratamentos médicos e cirúrgicos currentemente disponíveis, são necessárias novas tecnologias para melhorar os resultados e minimizar o desconforto dos doentes. Recentemente, estudos preliminares de experimentação animal e em 3 doentes tratados, sugeriram a embolização arterial prostática selectiva (EAPS) como hipótese terapêutica para a HBP. Decidimos investigar se a EAPS poderia ser um procedimento bem sucedido no tratamento da HBP gravemente sintomática. Para tal realizámos um estudo anátomo-radiológico e clínico em 63 doentes com recurso a uma terapêutica inovadora minimamente invasiva guiada pela imagem. Avaliámos 126 hemipélvis com recurso a Angio-RM, Angio-TC e Angiografia Digital de Subtracção, com o intuito de definir os padrões básicos de bifurcação das artérias ilíacas internas até agora apenas descritos em estudos cadavéricos. Estudámos ainda o suprimento vascular arterial prostático, identificando: 1 as artérias prostáticas; 2 origem e direcção; 3 os ramos intra-prostáticos; 4 anastomoses com outras artérias. Em relação aos resultados anatómicos, identificámos 181 artérias prostáticas, já que em 43.7% das hemipélvis existiam dois pedículos arteriais prostáticos com origens independentes. A origem mais frequente foi a artéria pudenda interna (39.7%), seguida do tronco comum glúteo-pudendo (21%) e da artéria vesical superior (18.2%). Origens menos frequentes foram a artéria obturadora (12.1%), as artérias glúteas inferior (3.9%)ou superior (1.7%), ramos rectais provenientes da artéria mesentérica inferior (1.7%) e a artéria pudenda acessória (1.7%). Identificaram-se anastomoses com as artérias adjacentes em 57.9% dos casos: com a terminação da artéria pudenda interna (41.6%),artérias prostáticas contra-laterais (18.2%) e homo-laterais (11.7%), com ramos rectais (15.6%) e com artérias vesicais (12.9%). Em relação ao estudo clínico tratámos 63 doentes (idades compreendidas entre 52 - 82 anos, média 69.5 anos) com HBP gravemente sintomática refractária à terapêutica médica há mais de 6 meses. Foi possível avaliação após o tratamento em 37 doentes: média de seguimento de 4.7 meses (variando entre 1 e 12 meses). A EAPS unilateral foi possível em todos os doentes, com embolização bilateral em 73% dos casos. A embolização bilateral não foi possível em 27% dos casos devido a tortuosidade, alterações ateroescleróticas e pequeno calibre das artérias ilíacas e/ou prostáticas. Em média houve uma melhoria do International Prostate Symptom Score (IPSS) de 10.8 pontos, da QoL de 1.5 pontos e do Internationl Index of Erectile Function (IIEF) de 2.1 pontos. Houve uma redução média do PSA de 30% (2.4 ng/mL), um aumento do pico de fluxo urinário (Qmax) de 3.1 - 3.85 mL/s e uma redução média do volume prostático de 21% (18.5 mL). Registou-se uma complicação major: pequena área de isquémia da parede vesical tratada cirurgicamente. Em 75% dos doentes tratados obteve-se sucesso clínico com franca melhoria dos sintomas, enquanto 25% dos doentes foram considerados insucesso clínico por se ter registado uma fraca ou ausente melhoria sintomática após a embolização. Os restantes doentes tratados estão sob controlo evolutivo, pararam toda a medicação prostática, sem qualquer caso de disfunção sexual associada com o tratamento. Este trabalho constitui o primeiro estudo anatómico descritivo in vivo das artérias prostáticas, conseguido devido à utilização de técnicas de imagem nunca usadas para este fim. O uso clínico dos dados anatómicos acima referidos permitiu a implementação de técnicas de Radiologia de Intervenção no tratatamento de uma doença de elevada prevalência. ------------------------------- ABSTRACT: Benign prostatic hyperplasia (BPH) has high prevalence in men aged 50–79 years being ubiquitous with aging. Due to significant morbi-mortality associated with currently available medical and surgical treatments, there is the need for innovative technologies to continue to improve outcomes and minimize patient discomfort and morbidity. Recently, prostatic arterial embolization (PAE) was suggested as a treatmentoption for BPH based on preliminary results from animal studies and 3 treated patients. We decided to investigate if PAE might be a successful treatment option for severely symptomatic BPH patients. We performed a clinical and anatomical-radiological study in 63 patients with the use of an inovative image-guided minimally invasive technique. We evaluated 126 pelvic sides using Angio-MR or Angio-CT and Catheter Angiography before embolisation to treat symptomatic BPH. We aimed to define the main branching patterns of the male internal iliac arteries, so far only studied in the cadaver. We also evaluated the prostatic arterial supply, identifying: 1 the prostatic arteries; 2 origin and direction; 3 intra-prostatic branches; 4 anastomoses with surrounding arteries. Regarding the anatomical study we identified 181 prostatic arteries, because in 43.7% of pelvic sides 2 separate prostatic vascular pedicles were found. The most frequent origin was the internal pudendal artery (39.7%) with the common glutealpudendal trunk (21%) and superior vesical arteries (18.2%) the next commonest. Less frequent origins were the obturator artery (12.1%), the inferior (3.9%) or superior (1.7%) gluteal arteries, rectal branches from the inferior mesenteric artery (1.7%) and the accessory pudendal artery (1.7%). There were anastomoses with the surrounding arteries in 57.9% of cases: termination of the internal pudendal artery (41.6%), contralateral prostatic arteries (18.2%), same-side prostatic arteries (11.7%), rectal branches (15.6%), and vesical arteries (12.9%).Regarding the clinical study, we treated 63 patients aged 52–82 years (mean 69.5 years) who presented with symptomatic BPH refractory to medical treatment for at least 6 months. Follow-up evaluation (mean 4.7 months, range 1-12 months) was possible in 37 patients. PAE was achieved in all patients with bilateral embolization in 73%. In 27% PAE was performed unilaterally due to tortuosity, atherosclerotic changes and small size of iliac and prostatic arteries. There was a mean decrease in the IPSS of 10.8 points, a mean improvement in QoL of 1.5 points, and a mean increase in the sexual function score of 2.1 points. There was a mean PSA reduction of 30% (2.4 ng/mL), a Qmax increase of 3.1 to 3.85 mL/sec, and a mean prostate volume decrease of 21% (18.5 mL). There was one major complication: a small area of bladder wall ischemia treated by surgery. Overall, 75% of patients were considered clinical success with major improvement after PAE, while 25% of patients were considered clinical failure with little or no improvement after PAE. All remaining patients are under follow-up, stopped all prostatic medication, and reported no sexual dysfunction. This study is the first one to describe the radiological anatomy of the prostatic arteries, with the use of imaging techniques never used for this purpose before. The clinical use of the anatomical findings allowed the implementation of Interventional Radiology tehniques in the treatment of a disease with a high prevalence.

Dissecção Carotídea. Cinco Variações Sobre um Tema

A dissecção da artéria carótida interna é uma causa de AVC isquémico, particularmente em doentes jovens, sem aparentes factores de risco cérebro-vasculares. Métodos: Os autores descrevem o quadro clínico e achados imagiológicos (TAC, RMN e angiografia de subtracção digital) de cinco doentes internados consecutivamente na Unidade Cérebro-Vascular do Hospital de S. José, num período de dois meses, com o diagnóstico de oclusão da artéria carótida interna por provável dissecção. Discussão: O conjunto de casos clínicos apresentados salienta a heterogeneidade de formas de apresentação desta patologia, quer do ponto de vista clínico, quer imagiológico.

Prostatic Arterial Supply: Anatomic and Imaging Findings Relevant for Selective Arterial Embolization

PURPOSE: To describe the anatomy and imaging findings of the prostatic arteries (PAs) on multirow-detector pelvic computed tomographic (CT) angiography and digital subtraction angiography (DSA) before embolization for symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: In a retrospective study from May 2010 to June 2011, 75 men (150 pelvic sides) underwent pelvic CT angiography and selective pelvic DSA before PA embolization for BPH. Each pelvic side was evaluated regarding the number of independent PAs and their origin, trajectory, termination, and anastomoses with adjacent arteries. RESULTS: A total of 57% of pelvic sides (n = 86) had only one PA, and 43% (n = 64) had two independent PAs identified (mean PA diameter, 1.6 mm ± 0.3). PAs originated from the internal pudendal artery in 34.1% of pelvic sides (n = 73), from a common trunk with the superior vesical artery in 20.1% (n = 43), from the anterior common gluteal-pudendal trunk in 17.8% (n = 38), from the obturator artery in 12.6% (n = 27), and from a common trunk with rectal branches in 8.4% (n = 18). In 57% of pelvic sides (n = 86), anastomoses to adjacent arteries were documented. There were 30 pelvic sides (20%) with accessory pudendal arteries in close relationship with the PAs. No correlations were found between PA diameter and patient age, prostate volume, or prostate-specific antigen values on multivariate analysis with logistic regression. CONCLUSIONS: PAs have highly variable origins between the left and right sides and between patients, and most frequently arise from the internal pudendal artery.

Coronary Revascularization Induces a Shift From Cardiac Toward Noncardiac Mortality Without Improving Survival in Vascular Surgery Patient

OBJECTIVE: Although evidence has shown that ischemic heart disease (IHD) in vascular surgery patients has a negative impact on the prognosis after surgery, it is unclear whether directed treatment of IHD may influence cause-specific and overall mortality. The objective of this study was to determine the prognostic implication of coronary revascularization (CR) on overall and cause-specific mortality in vascular surgery patients. METHODS: Patients undergoing surgery for abdominal aortic aneurysm, carotid artery stenosis, or peripheral artery disease in a university hospital in The Netherlands between January 2003 and December 2011 were retrospectively included. Survival estimates were obtained by Kaplan-Meier and Cox regression analysis. RESULTS: A total of 1104 patients were included. Adjusted survival analyses showed that IHD significantly increased the risk of overall mortality (hazard ratio [HR], 1.50; 95% confidence interval, 1.21-1.87) and cardiovascular death (HR, 1.93; 95% confidence interval, 1.35-2.76). Compared with those without CR, patients previously undergoing CR had similar overall mortality (HR, 1.38 vs 1.62; P = .274) and cardiovascular mortality (HR, 1.83 vs 2.02; P = .656). Nonrevascularized IHD patients were more likely to die of IHD (6.9% vs 35.7%), whereas revascularized IHD patients more frequently died of cardiovascular causes unrelated to IHD (39.1% vs 64.3%; P = .018). CONCLUSIONS: This study confirms the significance of IHD for postoperative survival of vascular surgery patients. CR was associated with lower IHD-related death rates. However, it failed to provide an overall survival benefit because of an increased rate of cardiovascular mortality unrelated to IHD. Intensification of secondary prevention regimens may be required to prevent this shift toward non-IHD-related death and thereby improve life expectancy.

Atherogenesis and atherosclerosis in primary antiphospholipid syndrome

ABSTRACT: In the late seventies the term “Haematological Stress Syndrome” defined some haematological abnormalities appearing in the course of acute and chronic disorders, such as raised plasma levels of fibrinogen (FNG) and factor VIII, reduced fibrinolytic activity and hyperviscosity. In the early nineties the “Membrane stress syndrome hypothesis” proposed the unification of the concepts of haematological stress syndrome with those of oxidation, inflammation and immune activation to explain the pathogenesis of the antiphospholipid syndrome (APS) Antiphospholipid antibodies, coagulation, fibrinolysis and thrombosis. This chapter investigated the occurrence of the “Haematological Stress Syndrome” and thrombosis in 144 participants positive for aPL detected by clotting and immune tests. Among the clotting assays for the detection of lupus anticoagulant, dilute Russell's viper venom time better correlated with a history of venous thrombosis than activated partial thromboplastin time (p<0.0002 vs p<0.009) and was the only test correlated with a history of arterial thrombosis (p<0.01). By regression analysis, serum levels of IgG anticardiolipin antibodies (aCL) associated with the number of venous occlusions (p<0.001). With regards to FNG and von Willebrand factor (vWF), the former rose by 36% (95% CI; 21%, 53%) and the latter by 50% (95% CI; 29%, 75%) at the first venous occlusion and remained unchanged after subsequent occlusions. At variance FNG rose by 45% (95% CI; 31%, 60%) per arterial occlusion and vWF by 27% (95% CI; 10%, 47%) per arterial occlusion throughout. The coagulation/fibrinolytic balance was cross-sectionally evaluated on 18 thrombotic PAPS patients, 18 subjects with persistence of idiopathic aPL and in healthy controls. Markers of thrombin generation prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and of fibrin turnover D-Dimer (D-D) were higher in thrombotic (p=0.006)and non-thrombotic subjects (p=0.0001) than in controls as were those of D-D (p<0.0001 and p=0.003 respectively). TAT levels did not differ. Gender analysed data revealed blunted tPA release (hence a negative venous occlusion test) in thrombotic females but neither in thrombotic males (p=0.01) nor in asymptomatic subjects of either sex. Also, in both patient groups females had higher mean PAI than males (p<0.0002) and control females (p<0.02). The activity of factor XIII (FXIIIa) was evaluated was evaluated in 29 patients with PAPS, 14 persistent carriers of aPL without thrombosis, 24 thrombotic patients with inherited thrombophilia, 28 healthy controls and 32 patients with mitral and aortic valve prosthesis as controls for FXIII only. FXIIIa was highest in PAPS (p=0.001), particularly in patients with multiple (n=12) than single occlusion (p=0.02) and in correlation with PAI (p=0.003) and FNG (p=0.005). Moreover FXIIIa was strongly associated with IgG aCL and IgG anti-2GPI (p=0.005 for both) in the PAPS group and to a lesser degree in the aPL group (FXIIIa with IgG aCL, p=0.02, with IgG anti-2GPI, p=0.04). Altogether these results indicate: 1) a differential relationship of aPL, vWF and FNG with venous and arterial thrombosis; 2) heightened thrombin generation, accelerated fibrin turnover and fibrinolysis abnormalities also in asymptomatic carriers of aPLs; 3) enhanced FXIIIa that may contribute to atherothrombosis via increased fibrin/fibrinogen cross-linking. Lipid profile, lipid peroxidation and anti-lipoprotein antibodies in thrombotic primary antiphospholipid syndrome. Given the atherogenic lipid profile of SLE, the same possibility was explored in PAPS by comparing high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (CHO), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), triglycerides (TG), anti-lipoprotein antibodies, beta-2-glycoprotein I complexed to oxidized low-density lipoprotein (oxLDL-2GPI) and C-reactive protein (CRP) in 34 thrombotic PAPS patients compared to 36 thrombotic patients with inherited thrombophilia (IT), to 18 subjects persistently positive for antiphospholipid antibodies (aPL) with no underlying autoimmune or non-autoimmune disorders and to 28 healthy controls. Average concentrations of HDL (p<0.0001), LDL (p<0.0001), CHO (p=0.0002), ApoAI (p=0.002) were lower in PAPS whereas average TRY was higher (p=0.01) than other groups. Moreover PAPS showed higher IgG anti-HDL (p=0.01) and IgG anti-ApoAI (p<0.0001) as well as greater average oxLDL-2GPI (p=0.001) and CRP (p=0.003). Within PAPS, IgG anti-HDL correlated negatively to HDL (p=0.004) and was an independent predictor of oxLDL-2GPI (p=0.009). HDL and ApoAI correlated negatively with CRP (p=0.001 and p=0.007, respectively). IgG anti-HDL may hamper the antioxidant and anti-inflammatory effect of HDL favouring low-grade inflammation and enhanced oxidation in thrombotic PAPS. Indeed plasma 8-epi-prostaglandin F2α (a very specific marker of lipid peroxidation) was significantly higher in 10 patients with PAPS than 10 age and sex matched healthy subjects (p=0.0002) and strongly related to the titre of plasma IgG aCL (r=0.89, p=0.0004). Hence oxidative stress, a major player in atherogenesis, also characterises PAPS. Nitric oxide and nitrative stress in thrombotic primary antiphosholipid syndrome. Oxidative stress goes hand in hand with nitrative stress and to address the latter plasma nitrotyrosine (NT, marker of nitrative stress), nitrite (NO2-) and nitrate (NO3-) were measured in 46 thrombotic PAPS patients, 21 asymptomatic but persistent carriers of antiphospholipid antibodies (PCaPL), 38 patients with inherited thrombophilia (IT), 33 patients with systemic lupus erythematosus (SLE) and 29 healthy controls (CTR). Average crude NT was higher in PAPS and SLE (p=0.01) whereas average plasma NO2- was lower in PAPS and average NO3- highest in SLE (p<0.0001). In PAPS, IgG aCL titer and number of vascular occlusions negatively predicted NO2-, (p=0.03 and p=0.001, respectively) whereas arterial occlusions and smoking positively predicted NO3- (p=0.05 and p=0.005). Moreover CRP (an inflammatory marker) positively predicted NT (p=0.004). Nitric oxide metabolites relates to type and number of vascular occlusions and to aPL titers, whereas nitrative stress relates to low grade marker) positively predicted NT (p=0.004). Nitric oxide metabolites relates to type and number of vascular occlusions and to aPL titers, whereas nitrative stress relates to low grade inflammation and both phenomena may have implications for thrombosis and atherosclerosis in PAPS Inflammation and immune activation in thrombotic primary antiphospholipid syndrome. To investigate inflammation and immune activation in thrombotic PAPS high-sensitivity CRP (hs-CRP), serum amyloid A (SAA), oxLDL-2GPI, CRP bound to oxLDL-2GPI (CRP-oxLDL-2GPI) (as inflammatory markers) neopterin (NPT) and soluble CD14 (sCD14) (as immune activation markers) were measured by ELISA in 41 PAPS patients, in 44 patients with inherited thrombophilia (IT) and 39 controls (CTR). Compared to other groups, PAPS presented with higher plasma concentrations of inflammatory, hs-CRP (p=0.0004), SAA (p<0.01), CRP-oxLDL-2GPI (p=0.0004) and immune activation markers, NPT (p<0.0001) and sCD14 (p=0.007). By regression analysis SAA independently predicted thrombosis number (p=0.003) and NPT independently predicted thrombosis type (arterial, p=0.03) and number (p=0.04). These data confirm that low-grade inflammation and immune activation occur and relate to vascular features of PAPS. Antiphosholipid antibodies, haemostatic variables and atherosclerosis in thrombotic primary antiphospholipid syndrome To evaluate whether IgG aCL titre, haemostatic variables and the lipid profile bore any relationship to the intima media thickness (IMT) of carotid arteries high-resolution sonography was applied to the common carotid (CC), carotid bifurcation (CB) and internal carotid (IC) of 42 aPL subjects, 29 with primary thrombotic antiphospholipid syndrome and 13 with persistence of aPL in the absence of any underlying disorder. The following were measured: plasma FNG, vWF, PAI, homocysteine (HC), CHO, TG, HDL, LDL, platelet numbers and aCL of IgG and IgM isotype. By multiple regression analysis, IgG aCL titre independently predicted IMT at all carotid segments examined (p always <0.005). Plasma FNG and HC independently predicted IMT at the CB (p=0.001 and p<0.0001, respectively) and IC (p=0.03 and p<0.0001, respectively). These data strongly support an atherogenic role for IgG aCL in patients with aPL in addition to traditional risk factors. The atherosclerosis hypothesis was investigated in an age and sex-matched case-double-control study including 49 thrombotic PAPS patients (18 M, 31 F, mean age 37 ± 11), 49 thrombotic patients for IT and 49 healthy subjects. Average IMT was always greater in PAPS than control patients (CC: p=0.004, CB: p=0.013, IC: p=0.001). By dividing participants into age tertiles the IMT was greater in the second (CC: p=0.003, CB: p=0.023, IC: p=0.003) and third tertiles (CC: p=0.03, CB: p=0.004, IC: p=0.007). Conclusion: Coagulation activation, fibrinolysis depression, hightened fibrin turnover, oxidative and nitrative stress in parallel with low grade inflammation and immune activation characterise thrombotic PAPS: all these are early atherogenic processes and contribute to the demonstrated premature atherosclerosis that should be considered a clinical feature of PAPS.

Acute pleuropulmonary complications detected by computed tomography following myocardial revascularization

INTRODUCTION: Pleuropulmonary changes are common following coronary artery bypass grafting surgery performed with a saphenous vein graft, with or without an internal mammary artery. The presence of atelectasis or pleural effusions reflects the thoracic trauma. PURPOSE: To define the postoperative incidence of changes in the lung and in the pleural space and to evaluate the influence of the trauma. METHODS: Thirty patients underwent elective coronary artery bypass grafting surgery (8 saphenous vein grafts and 22 saphenous vein grafts and internal mammary artery grafts with pleurotomy). Chest tubes in the left pleural space were used in all internal mammary artery patients. On the second (day 2) and seventh (day 7) postoperative day, patients underwent a computed tomography, and pleural effusions were rated as follows: grade 0 = no fluid to grade 4 = fluid in more than 75% of the hemithorax. Atelectasis was rated as follows: laminar = 1, segmental = 3, and lobar = 10 points. RESULTS: All patients had pleural effusion or atelectasis. Between day 2 and day 7, the number of patients with effusions or atelectasis on the right side decreased (P < 0.05). The incidence of effusions on day 2 in the saphenous vein graft group (87.5%) was higher (P < 0.05) than in the internal mammary artery group (52.3%). The incidence of atelectasis in the lower right lobe decreased (P < 0.05) from 86.7% (day 2) to 26.7% (day 7). The degree of atelectasis in both sides did not differ on day 2 (P = 0.42) but did on day 7 (P < 0.0001). There was a decrease in the atelectasis from day 2 to day 7 on the right side (P < 0.001), but not on the left (P = 0.21). On day 2 there was a relationship between atelectasis and effusion on the right (P = 0.04), but not on the left (P = 0.113). CONCLUSION: The present series demonstrates that there is a high incidence of both minimal pleural effusion and atelectasis after coronary artery bypass grafting surgery, which drops on the right side from day 2 to day 7 post surgery. Factors that contribute to the persistence of changes on the left side include the thoracic trauma and the presence of chest tubes and pericardial effusion.

Arterial distensibility as a possible compensatory mechanism in chronic aortic regurgitation

OBJECTIVE: To evaluate elastic properties of conduit arteries in asymptomatic patients who have severe chronic aortic regurgitation. METHODS: Twelve healthy volunteers aged 30±1 years (control group) and 14 asymptomatic patients with severe aortic regurgitation aged 29±2 years and left ventricular ejection fraction of 0.61±0.02 (radioisotope ventriculography) were studied. High-resolution ultrasonography was performed to measure the systolic and diastolic diameters of the common carotid artery. Simultaneous measurement of blood pressure enabled the calculation of arterial compliance and distensibility. RESULTS: No differences were observed between patients with aortic regurgitation and the control group concerning age, sex, body surface, and mean blood pressure. Pulse pressure was significantly higher in the aortic regurgitation group compared with that in the control group (78±3 versus 48±1mmHg, P<0.01). Arterial compliance and distensibility were significantly greater in the aortic regurgitation group compared with that in the control group (11.0±0.8 versus 8.1±0.7 10-10 N-1 m4, P=0.01 e and 39.3±2.6 versus 31.1±2.0 10-6 N-1 m², P=0.02, respectively). CONCLUSION: Patients with chronic aortic regurgitation have increased arterial distensibility. Greater vascular compliance, to lessen the impact of systolic volume ejected into conduit arteries, represents a compensatory mechanism in left ventricular and arterial system coupling.

Debranching Solutions in Endografting for Complex Thoracic Aortic Dissections

Background: Conventional surgical repair of thoracic aortic dissections is a challenge due to mortality and morbidity risks. Objectives: We analyzed our experience in hybrid aortic arch repair for complex dissections of the aortic arch. Methods: Between 2009 and 2013, 18 patients (the mean age of 67 ± 8 years-old) underwent hybrid aortic arch repair. The procedural strategy was determined on the individual patient. Results: Thirteen patients had type I repair using trifurcation and another patient with bifurcation graft. Two patients had type II repair with replacement of the ascending aorta. Two patients received extra-anatomic bypass grafting to left carotid artery allowing covering of zone 1. Stent graft deployment rate was 100%. No patients experienced stroke. One patient with total debranching of the aortic arch following an acute dissection of the proximal arch expired 3 months after TEVAR due to heart failure. There were no early to midterm endoleaks. The median follow-up was 20 ± 8 months with patency rate of 100%. Conclusion: Various debranching solutions for different complex scenarios of the aortic arch serve as less invasive procedures than conventional open surgery enabling safe and effective treatment of this highly selected subgroup of patients with complex aortic pathologies.