Advanced imaging study in cerebrovascular pathology for the personalization of therapy: from the capillary microcirculation to the vessel wall

Objectives: To investigate the use of intravascular optical coherence tomography (IVOCT) for carotid artery stenting (CAS) procedures in patients with atherosclerotic stenosis. Examine possible markers that might identify the onset of new cerebral ischemic lesions on MRI. Specifically, attention was drawn to the morphological features of the used dual layer stent, which could be underestimated during traditional CAS procedures. Secondary goals are to compare the safety and efficacy of different CAS techniques and the accuracy of the vessel analysis software’s on pre-operative CTA examination used to quantify ICA stenosis with the gold standard IVOCT. Material and Methods: Ten patients underwent CAS procedure with flow-arrest technique and IVOCT evaluations prior to and following stent deployment, while five matched patients underwent CAS procedure with distal embolic protection device (EPD) technique. All patients underwent 24-hours 3T MRI examination to check for ischemic lesions; all patients were treated with the same dual-layer stent. Results: Patients with new ischemic lesions demonstrated peculiar stent configuration in the distal end, and a strong Spearman’s rank order correlation was found among the volume of new DWI lesions and the stent configuration in its distal end (Rs: 0.81; p <0.001). No statistically significant differences were observed in the total burden of new ischemic lesions for each technique. The vessel analysis software's on CTA comparison demonstrated a higher diagnostic accuracy in the degree of ICA stenosis compared to the gold standard of IVOCT of the specialized software (ROC curve = 0.63; p = 0.06) compared to the general software (ROC curve = 0.57, p = 0.31). Conclusions: Study’s results support the use of IVOCT to allow recognition of potential features that can predict the onset of new cerebral ischemic lesions. Additionally, IVOCT made it possible to evaluate specialized software's increased accuracy in the pre-operative evaluation of ICA atherosclerotic stenosis.

The Soluble Guanylyl Cyclase Activator Bay 60-2770 Potently Relaxes The Pulmonary Artery On Congenital Diaphragmatic Hernia Rabbit Model.

Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypertension which is often difficult to manage, and a significant cause of morbidity and mortality. In this study, we have used a rabbit model of CDH to evaluate the effects of BAY 60-2770 on the in vitro reactivity of left pulmonary artery. CDH was performed in New Zealand rabbit fetuses (n = 10 per group) and compared to controls. Measurements of body, total and left lung weights (BW, TLW, LLW) were done. Pulmonary artery rings were pre-contracted with phenylephrine (10 μM), after which cumulative concentration-response curves to glyceryl trinitrate (GTN; NO donor), tadalafil (PDE5 inhibitor) and BAY 60-2770 (sGC activator) were obtained as well as the levels of NO (NO3/NO2). LLW, TLW and LBR were decreased in CDH (p < 0.05). In left pulmonary artery, the potency (pEC50) for GTN was markedly lower in CDH (8.25 ± 0.02 versus 9.27 ± 0.03; p < 0.01). In contrast, the potency for BAY 60-2770 was markedly greater in CDH (11.7 ± 0.03 versus 10.5 ± 0.06; p < 0.01). The NO2/NO3 levels were 62 % higher in CDH (p < 0.05). BAY 60-2770 exhibits a greater potency to relax the pulmonary artery in CDH, indicating a potential use for pulmonary hypertension in this disease.

Implantation Of Transcatheter Aortic Valve Prosthesis Through The Ascending Aorta Concomitant With Coronary Artery Bypass Grafting Without Cardiopulmonary Bypass.

Introdution: The transcatheter aortic valve implantation in the treatment of high-risk symptomatic aortic stenosis has increased the number of implants every year. The learning curve for transcatheter aortic valve implantation has improved since the last 12 years, allowing access alternatives. The aim of this study is to approach the implantation of transcatheter aortic valve through transaortic via associated with off-pump cardiopulmonary bypass surgery in a 67-year-old man, with chronic obstructive pulmonary disease, arterial hypertension and kidney transplant. Off-pump coronary artery bypass surgery was performed and the valve in the aortic position was released successfully. There were no complications in the intraoperative and postoperative period. Gradient reduction, effective orifice increasing of the prosthesis and absence of valvular regurgitation after implantation were observed by transesophageal echocardiography. Procedural success demonstrates that implantation of transcatheter aortic valve through the ascending aorta associated with coronary artery bypass surgery without CPB is a new option for these patients.

Enhanced Endothelium-dependent Relaxation Of Rat Pulmonary Artery Following β-adrenergic Overstimulation: Involvement Of The No/cgmp/vasp Pathway.

The aim of this study was to investigate whether β-adrenoceptor (β-AR) overstimulation induced by in vivo treatment with isoproterenol (ISO) alters vascular reactivity and nitric oxide (NO) production and signaling in pulmonary arteries. Vehicle or ISO (0.3mgkg(-1)day(-1)) was administered daily to male Wistar rats. After 7days, the jugular vein was cannulated to assess right ventricular (RV) systolic pressure (SP) and end diastolic pressure (EDP). The extralobar pulmonary arteries were isolated to evaluate the relaxation responses, protein expression (Western blot), NO production (diaminofluorescein-2 fluorescence), and cyclic guanosine 3',5'-monophosphate (cGMP) levels (enzyme immunoassay kit). ISO treatment induced RV hypertrophy; however, no differences in RV-SP and EDP were observed. The pulmonary arteries from the ISO-treated group showed enhanced relaxation to acetylcholine that was abolished by the NO synthase (NOS) inhibitor N(ω)-nitro-l-arginine methyl ester (l-NAME); whereas relaxation elicited by sodium nitroprusside, ISO, metaproterenol, mirabegron, or KCl was not affected by ISO treatment. ISO-treated rats displayed enhanced endothelial NOS (eNOS) and vasodilator-stimulated phosphoprotein (VASP) expression in the pulmonary arteries, while phosphodiesterase-5 protein expression decreased. ISO treatment increased NO and cGMP levels and did not induce eNOS uncoupling. The present data indicate that β-AR overactivation enhances the endothelium-dependent relaxation of pulmonary arteries. This effect was linked to an increase in eNOS-derived NO production, cGMP formation and VASP content and to a decrease in phosphodiesterase-5 expression. Therefore, elevated NO bioactivity through cGMP/VASP signaling could represent a protective mechanism of β-AR overactivation on pulmonary circulation.

Quality Of Life Of Coronary Artery Disease Patients After The Implementation Of Planning Strategies For Medication Adherence.

to compare the general and specific health-related quality of life (HRQoL) between the Intervention (IG) and Control (CG) groups of coronary artery disease patients after the implementation of Action Planning and Coping Planning strategies for medication adherence and to verify the relationship between adherence and HRQoL. this was a controlled and randomized study. the sample (n=115) was randomized into two groups, IG (n=59) and CG (n=56). Measures of medication adherence and general and specific HRQoL were obtained in the baseline and after two months of monitoring. the findings showed that the combination of intervention strategies - Action Planning and Coping Planning for medication adherence did not affect the HRQoL of coronary artery disease patients in outpatient monitoring.

The optical analysis of the abdominal wall using the biospeckle after implants of polypropylene mesh in rats

PURPOSE: To evaluate an experimental animal model to study the abdominal tissue activity considering its interaction with a polypropylene mesh, through the use of one of the optical phenomena of light Laser, the biospeckle. METHODS: Fifty Wistar male rats were divided into four groups: Group 1: ten animals not submitted to surgery; Group 2: ten animals submitted to surgery without polypropylene mesh; Group 3: 20 animals submitted to surgery followed by the mesh placement; Group 4: (sham) with ten animals. None of the animals presented post surgical complications being submitted to the optical tests at the 20th postoperative day. RESULTS: The analysis from the biospeckle tests, comparing the medians and standard deviations with T Student test, indicated that no significative difference was observed on the abdominal wall tissue activity in the four groups considered, with and without polypropylene mesh prosthesis implantation. CONCLUSION: The animal model is viable and the biospeckle open ways for a great number of experiments to be developed in evaluating tissue activity.

Modelo de suprimento sanguíneo do intestino grosso do tamanduá bandeira (Myrmecophaga tridactyla)

Em seis animais adultos Myrmecophaga tridactyla estudou-se o modelo de suprimento sanguíneo do intestino grosso, que é dependente das artérias mesentérica cranial (AMCr) e caudal (AMC). Os espécimes coletados conforme as normas do IBAMA (Instituto Brasileiro do Meio Ambiente e dos Recursos Naturais Renováveis) foram perfundidos com água (40 C), injetados com látex corado, fixados em formol e conservados em solução alcoólica (50%). O mesocólon está disposto na linha sagital mediana e fixa o intestino grosso à parede dorsal do abdome. Derivaram da AMC: a artéria retal cranial, sete a 14 artérias cólicas e uma ou duas artérias ileocólicas, que apresentaram anastomoses de irrigação com a AMCr. A AMC finaliza-se na borda mesocólica das alças intestinais, emitindo ramos cólicos retos a partir das arcadas justacólicas, que penetram na intimidade da musculatura longitudinal. Ao longo do trajeto da AMC foram observadas ilhas arteriais, e a região ileocólica apresentou maior densidade vascular.

Metabolic syndrome and dietary components are associated with coronary artery disease risk score in free-living adults: a cross-sectional study

Background: Coronary artery disease (CAD) is among the main causes of death in developed countries, and diet and lifestyle can influence CAD incidence. Objective: To evaluate the association of coronary artery disease risk score with dietary, anthropometric and biochemical components in adults clinically selected for a lifestyle modification program. Methods: 362 adults (96 men, 266 women, 53.9 +/- 9.4 years) fulfilled the inclusion criteria by presenting all the required data. The Framingham score was calculated and the IV Brazilian Guideline on Dyslipidemia and Prevention of Atherosclerosis was adopted for classification of the CAD risks. Anthropometric assessments included waist circumference (WC), body fat and calculated BMI (kg/m(2)) and muscle-mass index (MMI kg/m(2)). Dietary intake was estimated through 24 h dietary recall. Fasting blood was used for biochemical analysis. Metabolic Syndrome (MS) was diagnosed using NCEP-ATPIII (2001) criteria. Logistic regression was used to determine the odds of CAD risks according to the altered components of MS, dietary, anthropometric, and biochemical components. Results: For a sample with a BMI 28.5 +/- 5.0 kg/m(2) the association with lower risk (<10% CAD) were lower age (<60 years old), and plasma values of uric acid. The presence of MS within low, intermediary, and high CAD risk categories was 30.8%, 55.5%, and 69.8%, respectively. The independent risk factors associated with CAD risk score was MS and uric acid, and the protective factors were recommended intake of saturated fat and fiber and muscle mass index. Conclusion: Recommended intake of saturated fat and dietary fiber, together with proper muscle mass, are inversely associated with CAD risk score. On the other hand, the presence of MS and high plasma uric acid are associated with CAD risk score.

TCF7L2 Polymorphism rs7903146 Is Associated with Coronary Artery Disease Severity and Mortality

Background: TCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects. Methods and Results: two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR = 2.32 95% CI 1.27-4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004). Conclusions: rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets.

Genetic Variants of Diabetes Risk and Incident Cardiovascular Events in Chronic Coronary Artery Disease

Objective: To determine whether information from genetic risk variants for diabetes is associated with cardiovascular events incidence. Methods: From the about 30 known genes associated with diabetes, we genotyped single-nucleotide polymorphisms at the 10 loci most associated with type-2 diabetes in 425 subjects from the MASS-II Study, a randomized study in patients with multi-vessel coronary artery disease. The combined genetic information was evaluated by number of risk alleles for diabetes. Performance of genetic models relative to major cardiovascular events incidence was analyzed through Kaplan-Meier curve comparison and Cox Hazard Models and the discriminatory ability of models was assessed for cardiovascular events by calculating the area under the ROC curve. Results: Genetic information was able to predict 5-year incidence of major cardiovascular events and overall-mortality in non-diabetic individuals, even after adjustment for potential confounders including fasting glycemia. Non-diabetic individuals with high genetic risk had a similar incidence of events then diabetic individuals (cumulative hazard of 33.0 versus 35.1% of diabetic subjects). The addition of combined genetic information to clinical predictors significantly improved the AUC for cardiovascular events incidence (AUC = 0.641 versus 0.610). Conclusions: Combined information of genetic variants for diabetes risk is associated to major cardiovascular events incidence, including overall mortality, in non-diabetic individuals with coronary artery disease.

Effect of the effluent released from the canine internal mammary artery after intraluminal and extraluminal perfusion of acetylcholine and adenosine diphosphate

Segments of the canine internal mammary artery (35 mm in length) were suspended in vitro in an organ chamber containing physiological salt solution (95% O(2)/5% CO(2), pH = 7.4, 37 degrees C). Segments were individually cannulated and perfused at 5 ml/minute using a roller pump. Vasorelaxant activity of the effluent from the perfused internal mammary arteries was bioassayed by measuring the decrease in tension induced by the effluent of the coronary artery endothelium-free ring which had been contracted with prostaglandin F(2 alpha) (2 x 10(-6) M). Intraluminal perfusion of adenosine diphosphate (10(-5) M) induced significant increase in relaxant activity in the effluent from the perfused blood vessel. However, when adenosine diphosphate (10(-5) M) was added extraluminally to the internal mammary artery, no change in relaxant activity in the effluent was noted. In contrast, acetylcholine produced significant increase in the relaxant activity on the effluent of the perfused internal mammary artery with both intraluminal and extraluminal perfusion. The intraluminal and extraluminal release of endothelium-derived relaxing factor (EDRF) by acetylcholine (10(-5) M) can be inhibited by site-specific administration of atropine (10(-5) M). These experiments indicate that certain agonists can induce the release of EDRF only by binding to intravascular receptors while other agonists can induce endothelium-dependent vasodilatation by acting on neural side receptors.

Acute and chronic effects of exercise on inflammatory markers and B-type natriuretic peptide in patients with coronary artery disease

Few studies have prospectively addressed the effects of exercise in the inflammatory activity of patients with coronary artery disease (CAD). We sought to evaluate the consequences of an acute bout of exercise on inflammatory markers and BNP in untrained CAD patients before and after randomization to a training program. 34 CAD patients underwent a 50-min acute exercise session on a cycle-ergometer at 65% peak oxygen uptake before and after blood sampling. They were then randomized to a 4-month chronic exercise program (15 patients) or general lifestyle recommendations (19 patients), undergoing a new acute session of exercise after that. In the overall population, acute exercise caused a significant increase in C-reactive protein [CRP; 1.79 (4.49) vs. 1.94 (4.89) mg/L, P < 0.001], monokine induced by interferon-gamma [Mig; 351 (324) vs. 373 (330) pg/mL, P = 0.027] and vascular adhesion molecule-1 [VCAM-1; 226 (82) vs. 252 (110) pg/mL, P = 0.02]. After 4-months, in exercise-trained patients, there was a significant decrease in the inflammatory response provoked by the acute exercise compared to patients in the control group reflected by a significant decrease in the differences between rest and post-exercise levels of CRP [-0.29 (0.84) mg/L vs. -0.11 (0.21) mg/L, P = 0.05]. Resting BNP was also significantly lower in exercise-trained patients when compared to untrained controls [15.6 (16.2) vs. 9.7 (11.4) pg/mL, P = 0.04 and 19.2 (27.8) vs. 23.2 (27.5) pg/mL, P = 0.76; respectively]. Chronic exercise training might partially reverse the inflammatory response caused by acute exercise in CAD patients. These results suggest that regular exercise is an important nonpharmacological strategy to the improvement in inflammation in CAD patients.

Quality of life after coronary artery bypass surgery

This study assessed the quality of life (QoL) of 124 people with coronary artery disease who had coronary artery bypass surgery in a hospital in Brazil, by using the Modified Flanagan`s QoL instrument as the outcome measure. In addition, we studied the association between QoL and demographic, clinical, and perceived health status (using SF-36 Health Survey) measures. The mean for the Modified Flanagan`s QoL was high (M = 84.8, SD = 13.6) when compared to similar studies in the United States. In a linear regression analysis, the SF-36 subscales of vitality, and general and mental health were statistically significant (p < .01 for all), after adjusting for other demographic and clinical variables. Increasing values of those SF-36 subscales corresponded to increasing Modified Flanagan`s QoL. Despite the limitations of the study, this result suggests that future clinical interventions aimed to improve QoL in this population could focus on the patient`s psychological conditions after the surgery.

Analysis of PVC pipe-wall viscoelasticity during water hammer

This research work focuses on the analysis of hydraulic transients in polyvinyl chloride (PVC) pipes, which are characterized by a viscoelastic rheological behavior. Transient pressure data were collected in a pipe rig consisting of a set of PVC pipes. The creep function of the PVC pipes was determined by using an inverse transient model based on collected transient pressure data and compared with that obtained by carrying out mechanical tensile tests of PVC pipe specimens. The numerical results obtained from the transient solver have shown that the attenuation, dispersion, and shape of transient pressures were well described. The incorporation of the viscoelastic mechanical behavior in the hydraulic transient model has provided an excellent fitting between numerical results and observed data. Calibrated creep function based on inverse analysis fit the one determined by mechanical tests well, which emphasized the importance of pipe-wall viscoelasticity in hydraulic transients in PVC pipes.

Study of the influence of simultaneous variation of magnetic material microstructural features on domain wall dynamics

The magnetic Barkhausen noise (MBN) is a phenomenon sensitive to several kinds of magnetic material microstructure changes, as well as to variations in material plastic deformation and stress. This fact stimulates the development of MBN-based non-destructive testing (NDT) techniques for analyzing magnetic materials, being the proposition of such a method, the main objective of the present study. The behavior of the MBN signal envelope, under simultaneous variations of carbon content and plastic deformation, is explained by the domain wall dynamics. Additionally, a non-destructive parameter for the characterization of each of these factors is proposed and validated through the experimental results. (C) 2010 Elsevier B.V. All rights reserved.