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Background Previous studies have demonstrated that MMP-9 may be a predictor of atherosclerotic plaque instability and future adverse cardiovascular events, but longitudinal data on the association between MMP9 and coronary disease progression are lacking. Purpose This study is aimed at investigating whether MMP9 is associated with atherosclerotic plaque progression. Methods MMP9 serum levels were measured in stable patients with chronic coronary syndrome (CCS) undergoing coronary computed tomography angiography at baseline and after a period of 6.5±1.1 years of follow up to assess progression of Total, Fibrous, Fibro-fatty, Necrotic Core, and Dense Calcium plaque volume (PV). The relationship of serum MMP9 with plaque progression was assessed using linear regression analysis, adjusting for clinical variables including, age, sex, risk factors, medical therapy, LDL-C, TG/HDL-C ratio, hs-CRP, and the presence of obstructive CAD (>50% coronary stenosis in at least one major coronary vessels). Results A total of 157 patients (58±8 years of age; 66% males) were included in the analysis, with median MMP9 values of 135±186 mg/dL (mean ± SD). Annual changes of Total, Fibrous-Fatty and Necrotic Core PV were significantly different across MMP9 tertiles (Figure 1). Multivariable linear regression analysis demonstrated a positive association between serum levels of MMP9 and annual change of Total and Necrotic Core PV (Figure 1). Conclusion Among patients with CCS, MMP9 serum levels were an independent predictor of progression of coronary plaque burden and, in particular, of adverse plaque features, such as Necrotic Core PV. This association was robust and independent from baseline traditional cardiovascular risk factors and medications, supporting for MMP9 a role as a novel marker of residual coronary risk. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Horizon 2020 - Project “Simulation Modeling of coronary ARTery disease: a tool for clinical decision support–SMARTool”

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Commission in the H2020 program: Project SMARTool, “Simulation Modeling of coronary ARTery disease: a tool for clinical decision support—SMARTool” Background and aims The coexistence of elevated plasma triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) may contribute to the residual cardiometabolic risk of coronary artery disease (CAD) independently of total cholesterol and low-density lipoprotein cholesterol (LDL-C) absolute plasma levels [1]. Aim of this study is to assess whether a high TG/HDL-C ratio is characterized by a specific lipidomics signature in statin users and its relationship with the coronary risk score defined by coronary computed tomography angiography (CTA). Methods TG/HDL-C ratio was calculated in 132 patients (68.8±7.7 years, 85 males) with suspected or known CAD referred to coronary CTA and receiving statins treatment in the last 6.3 ± 1.4 years before enrolment. Patients were grouped according to TG/HDL-C ratio quartiles: IQ (≤1.694), IIQ (1.695-2.399), IIIQ (2.400-3.281), and IVQ (>3.282). Coronary CTA exams were analysed according to the modified 17-segment American Heart Association classification [2] and interpretable segments were visually assessed for degree of stenosis and plaque composition. A comprehensive coronary risk score (CTA score) [3], previously validated as predictor of adverse outcome, was calculated in each patient. Except for subjects with normal arteries (CTA score = 0), all patients were classified into 3 groups of CTA score severity: low (score < 5), intermediate (score 5-20) and high (score > 20) risk [4]. Patient-specific plasma targeted lipidomics was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This approach allowed to quantify 69 circulating lipids encompassing six lipid classes (triacylglycerol [TG], phosphatidylcholine [PC], phosphatidylethanolamine [PE], ceramide [Cer], sphingomyelin [SM], cholesterol ester [CE]). Differential analysis was performed using TG/HDL-C and CTA score annotation. Results 18 altered lipid species in the group with higher TG/HDL-C ratio were also altered in the group with higher CTA risk score. This common set of lipids is composed of CE(16:0), CE(18:0), PC(38:2), 8 SM [SM(34:2), SM(38:2), SM(41:2), SM(41:1), SM(42:4), SM(42:3), SM(42:1), SM(43:3)], TG(52:1) and 6 PE [PE(34:0), PE(34:1), PE(34:2), PE(36:1), PE(36:2), PE(36:3)], and represents the lipidomics signature associating elevated plasma TG/HDL-C ratio with high CTA risk score in statin users. Conclusion In patients with stable CAD under statin treatment, a specific pattern of altered lipids, characterized by reduced plasma levels of cholesterol esters and sphingomyelins and increased levels of triacylglicerols and phosphatidylethanolamines, is associated with high TG/HDL-C ratio and high CTA score. This specific lipidomic signature identifies patients with higher residual cardiometabolic and coronary risk, not tackled by current lipid lowering therapy, unveiling possible new molecular targets of treatment.

Il progetto MenSana mira alla prevenzione primaria mediante strumento mobili di facile impatto. Gli obiettivi primari del progetto sono: 1. fornire agli utenti della mensastrumenti di automonitoraggio, allo scopo di stimolare la consapevolezza di sé e migliorare il controllo sulle proprie scelte alimentari, 2. Migliorare lo stato di salute e aumentare il benessere dell'utente. L'app intende stimolare l'utente nella selezione dei cibi più salutari e più appropriati al proprio profilo (in base alle patologie del soggetto) e monitorare l'introito calorico. Un database contiene tutta la bromatologia delle pietanze offerte a mensa e la valutazione da parte di dietologi/nutrizionisti della adeguatezza o meno delle pietanze rispetto alle patologie osservate. Gli alert sui cibi sono forniti in modo diretto ed intuitivo mediante icone che rappresentano faccine (neutre, sorridenti, tristi). In questo report si descrive il progetto grafico e funzionale dell'app Mensana

Dilated cardiomyopathy following ischemic disease increases the degree of heart failure and its surgical management remains controversial. The most challenging objective in the clinical decision making for the management of patients with myocardial dysfunction or overt heart failure (HF) is to choose the best option for improving myocardial function and the clinical outcome. Medical versus surgical and, among surgical options, coronary revascularization, myocardial restoration, mitral valve repair, are the proposed solutions for avoiding progression of cardiac dysfunction toward HF. Magnetic resonance imaging (MRI) can provide patient-specific identification of dysfunctioning left ventricular (LV) segments and recognition of not viable myocardium by gadolinium (GAD) late hyperenhancement pattern. Within EU project VPH2 we aimed at developing two software tools for the quantitatively prediction the postoperative mechanical performance of the complex left ventricle: a functional assessment tool (FAT) and a functional predictive tool (FTP). In particular, the former is aimed to the automatic extraction of contours from 4D MRI images and automatic calculation of global and regional parameters (e.g. EF, synchronicity) while the latter is aimed to the prediction of postoperative LV function through mechanical modeling.

In recent experiments, inhomogeneities in the somatic membrane potential of a firing neuron have been observed by Gogan et al. Ion channel interactions result in collective behavior which might lead to spontaneous symmetry breaking. The simulations presented in this paper show that, with a uniform distribution of ion channels, such spontaneous symmetry breaking is not to be expected. On the other hand, a nonuniform distribution of ion channels effectively leads to a nonuniform membrane potential distribution. The inhomogeneities therefore must reflect inhomogeneities in the spatial distribution of ion channels.

A number of epidemiological and clinical studies have linked elevated plasma homocysteine (Hcy) to atherosclerotic vascular disease affecting coronary, carotid, and peripheral vessels. Plasma Hcy can be considered a marker of methionine metabolic efficiency, mainly affected by dietary intake of vitamins, especially folate, vitamin B(6), and B(12), as well as by genetic mutations of key metabolic enzymes and renal elimination.

Atherosclerosis is a progressive disease characterized by inflammation, monocyte-macrophage migration, and lipid accumulation in the vascular wall. Atherosclerosis is initially characterized by endothelial dysfunction, which favors lipid and cell elements crossing inside blood vessel wall. In this study, two experiments are calculated numerically. The first is Cheng et al. 2006 experiment with cast model on the carotid artery and the second is our pig experiment on the left anterior descending coronary artery (LAD) after 2 months of high fat diet. Experimental model of plaque formation on pig LAD is simulated numerically using a specific animal data obtained from intravascular ultrasound (IVUS) and histological data. The 3D blood flow is governed by the Navier-Stokes equations, together with the continuity equation. Mass transfer within the blood lumen and through the arterial wall is coupled with the blood flow and is modeled by the convection-diffusion equation. LDL transport in lumen of the vessel is described by Kedem-Katchalsky equations. The inflammatory process is solved using three additional reaction-diffusion partial differential equations. Matching of IVUS and histological animal data is performed using 3D histological image reconstruction and 3D deformation of elastic body. Lipids concentration in the intimal area of the low shear stress was 16% and for oscillatory zone 10% which is in good agreement with experimental data. Computed concentration of macrophages for pig model indicates that there is a newly formed matter in the intima, especially in LAD 15 mm region below left main artery bifurcation where plaque 8% of the area intima thickness was found in the area of lowered shear stress. Matching of plaque location and progression in time between experimental and computer model shows a potential benefit for future prediction of this vascular decease using computer simulation.

International audience; The purpose of this paper is to present the linkage of Thetis (a real time multi-vehicles hybrid simulator for heterogeneous vehicles) with a control architecture for the management of contextual tasks on AUVs (Autonomous Underwater Vehicle), both developed at LIRMM (France). An AUV is mainly composed of an onboard informatics system and a set of sensors and actuators. We design a 3-layer control architecture (global supervisor, local supervisors, and a set of management modules which are in charge of the means of perception and actions), allowing for facing Hardware (embedded instrumentation) and software evolutions. Due to the complexity and the sophistication of the control of actual underwater systems, it is necessary to check the embedded robot controller, i.e. all its constitutive hardware and software sub-systems before beginning any real mission. To achieve this goal it's possible to call upon simulation, thus avoiding heavy and numerous experimentations. Thetis is able to provide the necessary environment to test real robots and their interactions (communication and collision detection). Indeed this simulator allows hardware in loop simulations with the support of virtual sensors. The paper first describes the architecture and functionalities of Thetis, then the control architecture of our AUVs is briefly presented. We conclude with the advantages of connecting the 2 systems together.

Most wild equids are currently endangered or threatened, as mentioned in the International Union for the Conservation of Nature Red List, and several domestic horse breeds are at risk of extinction. Genome resource banking requires cryoconservation of semen, oocytes, and/or embryos. Embryo production in equids is limited in vivo because routine induction of multiple ovulation is still ineffective. Embryo production in vitro allows the production of several embryos per cycle that could easily be frozen because of their small size. Intracytoplasmic sperm injection has been widely adopted to generate horse embryos in vitro; however, intracytoplasmic sperm injection is time-consuming and requires expensive equipment and expertise in micromanipulation. Several attempts to establish an efficient IVF technique in the equine were performed, but reported IVF rates remain quite low and no repeatable equine IVF technique was available. Our objective was to develop an efficient and repeatable IVF technique in the equine. Immature cumulus-oocyte complexes (COC) were collected either from slaughtered mares in a local slaughterhouse or from our experimental mares by ovum pick up (OPU). The COC were cultured for 26 h in an in vitro maturation (IVM) medium or in preovulatory follicular fluid (FF) collected by OPU, pre-incubated for 30 min in oviducal fluid collected from slaughtered females, co-incubated for 18 h with fresh spermatozoa treated with procain, and cultured in SOF for 30 h. They were fixed and analysed either after 18 h IVF (experiment 1) or after 30 h in vitro development (experiment 2). In experiment 1, COC were collected from slaughtered mares and analysed after 18 h IVF. Zygotes with 2 pronuclei were observed. The IVF rate was similar for oocytes matured in IVM medium (22/33, 67%) or FF (24/42, 57%; chi-square test, P > 0.05). In experiment 2, COC were collected from slaughtered mares and from experimental mares and analysed after 30 h of in vitro development. We observed zygotes with 2 highly decondensed pronuclei, pronuclei decondensation being the first step of embryo development. For oocytes collected from slaughtered mares, the percentage of zygotes was similar for oocytes matured in IVM medium (8/11, 73%) or FF (10/15, 67%). For oocytes collected by ovum pickup, the percentage was similar for IVM medium (3/5, 60%) or FF (6/8, 75%). We also observed some embryonic structures with several nuclei, but the quality of these embryos was poor. In conclusion, we have established an efficient IVM-IVF technique that allows the first step of embryo development. Because we obtained similar results for 4 years, we consider that this efficient technique is repeatable. Further experiments are in progress to improve the quality of the embryos.

Severe sepsis and septic shock have a mortality rate that may range between 28 and 50%. It is estimated that approximately 200,000 patients die per annum in the USA as a consequence of sepsis. The reduction of plasma endotoxin levels to achieve a favourable outcome for septic patients has been previously demonstrated but the effectiveness of treatments targeting single inflammatory mediators during established sepsis has been disappointing. Furthermore,some clinical study clinically showed valuable reduction in cytokine levels by hemofiltration alone. The prompt removal of endotoxins could be an effective way to reduce the immunological activation and the amount of NO produced by endotoxin-activated inducible NO-synthase in many tissues and cells. The polymyxin B cartridge is an extracorporeal hemoperfusion device (PMX-DHP) known to remove circulating endotoxins. Open-label clinical trials testing PMX-DHP have demonstrated its safety in the septic shock treatment while the overall survival rate significantly improved in comparison with the control groups. The purpose of this study was to investigate the effects of PMX-DHP on redox status, inflammatory cytokine profile, monocytes and PMN leukocyte activation in Gram-negative sepsis. Prospective study: six patients, 2 males and 4 females 60.5+/-24.5 years old, in ICU for severe Gram-negative sepsis (emergency surgery for intra abdominal infection). Two PMX-DHP runs, at T0 and T1; 2 hours each; the first within 24 hours from sepsis diagnosis or 12 hours after emergency surgery, the first PMX-DHP at T0, the second after 24 hours.; APACHE II score at T0: 20.1+/-3.7; SOFA score 14.2+/-2.5; organ failure: 3+/-1.5; norepinephrine(Ne) in 1 patient; Ne + dopamine (DA) in 4 patients; DA in 1 patient only. Mean dosage: Ne 0.24 mcg/kg/min; DA 8.9 mcg/kg/min. Four patients in CRRT (continuous veno-venous hemofiltration, AN69 hemofilter) for the entire length of the study. QB 100+/-10 ml/min. Pre and post PMX-DHP, plasma endotoxins as well as anti-IL 1-beta, IL2, IL4, IL5, IL6, IL8, IL10, TNF-alpha, GM-CSF, IFN-gamma levels were measured. Expression of CD64 on monocytes and PMN leukocytes and I -2r CD25 on CD4+ T cells by flow cytometry. Total and reduced plasma cysteine, homocysteine, glutathione (GSH); plasma glutathione peroxidase (GSH-Px) and reductase (GSH-Rx); erythrocyte GSH (eGSH), eGSH-Px and eGSH-Rx; NADP and NADPH and their ratio assessed pre and post PMX-DHP, all compared with 15 age and gender-matched healthy subjects for complete REDOX characterization.We observed a significant reduction of endotoxin levels post PMX-DHP; CD64 monocytes and PMN leukocytes overexpression returned to normal; pro-inflammatory cytokines Il6, Il 10 and TNF-alpha were significantly reduced. We detected no differences in plasma levels of anti-IL 1-beta, IL2, IL4, IL5, IL8, GM-CSF, IFN-gamma pre versus post PMX-DHP. SOFA score from 14.2+/-2.5 to 8.9+/-2.1 post PMX-DHP runs. Four out of six patients survived and were discharged; mortality was 33% versus the anticipated 51%.PMX-DHP reduces circulating endotoxins, down-activates monocytes and PMN leukocytes, reduces pro-Inflammatory cytokines and corrects the redox environment imbalance preventing oxidative damage to endothelial cells and the metabolic and functional microvascular derangements that usually lead to multi-organ failure and septic shock.

Central to the pathophysiology of sepsis and septic shock is an alteration in endothelial cell function and oxidative stress. Highly complex, integrated responses that include the activation of a number of cell types, inflammatory mediators and the hemostatic system are involved in endothelial dysfunction. On the other hand, the imbalance between the excessive production of reactive oxygen species and/or inadequate antioxidative defenses characterizes the oxidative stress. The overview of all these mechanisms suggests clinical biochemical markers as a possible therapeutic target together with correct intervention timing.

Total plasma homocysteine (tHcy) in children may be an useful biochemical marker for genetic risk of premature cardiovascular disease. We reported a rapid, isocratic HPLC method able to process very small amount of newborn plasma samples. A blood sample from heel capillary circulation was collected, using a heparinized capillary glass tube. Plasma sample from 1 to 10 microl was derivatized with ammonium-7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate after reduction with tri-n-butylphosphine and analyzed on Discovery C18 column, with a solution of acetonitrile-dihydrogenphosphate 0.1 M (8:92 v/v pH*2.1). This assay ensures a good recovery (95%), precision (CV 4.5%) and linearity (y=2.41x + 0.31, r=1). Due to its simplicity and reliability, our method is suitable for routine analysis of tHcy and other aminothiols (Cys, Cys-Gly, GSH) assessed for clinical and research purposes. With this HPLC method we have assayed tHcy levels in 1400 apparently healthy newborn babies (tHcy mean value=4.9+/-2.7 microM). In conclusion, this accurate and linear HPLC method allows measurement of tHcy in newborn during the routinary capillary blood collection in the fourth living day without any other invasive procedure.

Various models have been proposed to quantitate from [/sup 18/F]-Fluoro-Deoxy-Glucose ([/sup 18/F]FDG) positron emission tomography (PET) data glucose regional metabolic rate. The authors evaluate here four models, a three-rate constants (3 K) model, a four-rate constants (4 K) model, an heterogeneous model (TH) and a spectral analysis (SA) model. The data base consists of [/sup 18/F]FDG dynamic data obtained in the myocardium and brain gray and white matter. All models were identified by nonlinear weighted least squares with weights chosen optimally. The authors show that: 1) 3 K and 4 K models are indistinguishable in terms of parsimony criteria and choice should be made on parameter precision and physiological plausibility; in the gray matter a more complex model than the 3 K one is resolvable; 2) the TH model is resolvable in the gray but not in the white matter; 3) the classic SA approach has some unnecessary hypotheses built in and can be in principle misleading; the authors propose here a new SA model which is more theoretically sound; 4) this new SA approach supports the use of a 3 K model in the heart with a 60 min experimental period; it also indicates that heterogeneity in the brain is modest in the white matter; 5) [/sup 18/F]FDG fractional uptake estimates of the four models are very close in the heart, but not in the brain; 6) a higher than 60 min experimental time is preferable for brain studies.

Although the relationship between delayed 201Tl distribution and blood flow in acutely ischemic and infarcted myocardium has been widely explored in the experimental setting, its behaviour in chronically hypoperfused dysfunctioning human myocardium has not yet been evaluated.In tissue samples of excised failing hearts taken from ischemic (IHD) patients and idiopathic dilated cardiomyopathy (IDC) controls, we evaluated the relationship between delayed 201Tl retention (4 h redistribution), blood flow (assessed by means of 99mTc-labelled human albumin microspheres injected during transplantation) and biochemically-assessed fibrosis. 201Tl activity was expressed as the percent of the activity in the region with highest flow and the least fibrosis.Fibrosis and 201Tl activity were inversely related (r = -0.62, P = 0.0001). In IDC controls, low flows corresponded to uniformly preserved 201Tl retention. In IHD, 46 segments with flowsor = 0.60 ml.min-1.g-1 and 20 segments with flows0.60 ml.min-1.g1 showed matching delayed 201Tl retention and flow values; in the remaining 27, there was a disproportionately high tracer accumulation in comparison with flow (flow/201Tl mismatch). Despite significantly less fibrosis and lower flows, the mismatch segments showed significantly greater. 201Tl activity than the segments with concordantly high tracer retention and flow values. Conversely, at equivalent flow rates, the mismatch regions had less fibrosis than the areas with concordantly depressed 201Tl activity and perfusion.This super-normal 201Tl retention in hibernating myocardium may indicate a mechanism of cell adaptation to chronic hypoperfusion.

The mechanisms regulating coronary collateral circulation are largely unknown owing to both the complex and variable nature of clinical models and the difficulty to obtain quantitative and differentiated flow measurements within the various coronary tree portions. With the aim of assessing collateral flow reserve, we studied 19 patients with effort angina, without myocardial infarction and with isolated occlusion of either the left anterior descending coronary artery (n = 14) or the circumflex coronary artery (n = 5). Flow values were measured basally, during atrial pacing induced tachycardia and following ev dipyridamole infusion (0.56 mg/kg of body weight in 4 min), by means of positron emission tomography and nitrogen-13 ammonia as flow tracer, within both regions depending on collateral circulation and the remote ones. Results have been compared with those obtained in 13 normal subjects. Basal flow values in regions depending on collateral circulation and in the remote regions (0.61 +/- 0.11 vs 0.63 +/- 0.17 ml/min/g) were found to be similar, but lower than in normal subjects (1.00 +/- 0.20 ml/min/g, p0.01). During atrial pacing, flow increased to 0.83 +/- 0.25 and to 1.11 +/- 0.39 ml/min/g, in the regions depending on collateral circulation and in the remote regions, respectively (p0.05 as compared to baseline); again, values were lower than in normal subjects (1.86 +/- 0.61 ml/min/g, p0.01). Dipyridamole infusion further increased flow in the remote regions (1.36 +/- 0.57 ml/min/g, p0.01 as compared to atrial pacing) but it did not in the regions depending on collateral circulation (0.94 +/- 0.37 ml/min/g, NS as compared to atrial pacing); both values were lower than in normal subjects (3.46 +/- 0.78 ml/min/g, p0.01). Flow reserve in the regions depending on collateral circulation was found to have a direct linear correlation with the one in the remote regions (r = 0.83; p0.01). In conclusion, in spite of basal hypoperfusion, collateral circulation maintains a flow reserve which, even if reduced, is able to cope with moderate increments in oxygen consumption. An analogous flow reduction can be observed in the remote regions, suggesting that the entire coronary tree is involved, beyond the obstructive lesions of the main arterial branches.

The aims of this study were to assess the value of dobutamine echocardiography in identifying myocardial hibernation versus stunning and to elucidate the underlying pathophysiological mechanism of the contractile impairment.Twenty-one patients with isolated stenosis of the left anterior descending artery were evaluated 1 mo after thrombolysed acute anterior infarction. Regional function and blood flow were measured using echocardiography and PET at rest and during dobutamine administration (10 microg/kg/min).Defined by [18F]fluorodeoxyglucose uptake, 36 of 102 dyssynergic segments were necrotic, and 66 were viable. The latter segments were subdivided according to their [13N]ammonia flow distribution: 30 hibernating regions with perfusion defects (flow of80% of maximum) and 36 stunned areas with preserved resting perfusion (flow ofor =80% of maximum). Resting flows were similar in necrosis and hibernation (0.43 +/- 0.18 versus 0.47 +/- 0.16 ml x min(-1) x g(-1); not significant), and both resting values were lower than those seen in stunning (0.79 +/- 0.24; p0.05). Flow response to dobutamine was markedly reduced in necrosis (dobutamine/resting flow = 1.16 +/- 0.27), whereas it was maintained in hibernation (1.65 +/- 0.54) and stunning (1.42 +/- 0.57). Dobutamine improved function in a higher number of stunned (55%) than hibernating (16%) or necrotic (11%) segments.Dobutamine improves function mainly in stunned myocardium and does not reliably identify hibernation. The lack of functional response in hibernation is not related to an exhausted vasodilating capacity.

This study sought to investigate the angiographic or intracoronary Doppler variables of stenosis severity that best correlate with the results of dipyridamole echocardiography.Quantitative coronary angiography and intracoronary Doppler flow velocity assessments are the commonly used techniques for the objective identification of significant coronary artery stenosis.Thirty patients with an isolated lesion of the left anterior descending coronary artery (LAD) were studied by means of on-line quantitative coronary arteriography, intracoronary Doppler flow velocity measurements and dipyridamole echocardiography 6 months after percutaneous transluminal coronary angioplasty. The quantitative arteriographic analyses were performed on-line; post-stenotic Doppler flow velocities were measured at baseline and after adenosine infusion. Angiographic and Doppler measurements were compared with the corresponding dipyridamole echocardiographic data and analyzed by discriminant analysis.The dipyridamole echocardiographic response was positive in 11 patients (37%). The best cutoff values for predicting an abnormal echocardiographic response were 1) stenotic flow reserve of 2.8 (p = 0.0001); 2) 59% diameter stenosis (p = 0.0001); 3) minimal lumen diameter of 1.35 mm (p = 0.001); 4) coronary flow reserve of 2.0 (p = 0.0002); and 5) maximal peak velocity of 60 cm/s during hyperemia (p = 0.04). Multivariate analysis identified stenotic flow reserve as the only independent predictor of ischemia during dipyridamole echocardiography.Stenotic flow reserve is the variable that best describes the functional significance of an isolated LAD lesion, and a value of 2.8 is the best predictor of a positive dipyridamole echocardiographic response. Furthermore, angiographic variables of stenosis severity relate to echocardiographic test results better than intracoronary Doppler variables.

The structural correlates of 201Tl uptake in patients with advanced postischemic pump dysfunction are unclear. There are no good experimental models adequately reflecting the mixture of normal, dysfunctional but viable, and necrotic regions characteristic of chronic ischemic heart disease in human beings.Four heart transplant candidates with idiopathic dilated cardiomyopathy and seven with ischemic heart disease underwent rest-injection 4-hour redistribution 201Tl single-photon emission computed tomography before surgery. Delayed tracer uptake was categorized into severely reduced (50%), mildly or moderately reduced (50% to 74%), and normal (or =75%) and related to echocardiographic wall motion and histologic findings in the hearts excised at transplantation. In idiopathic dilated cardiomyopathy, despite severe wall motion impairment, minimal or mild myocardial damage and homogeneously high 201Tl uptake were found. In ischemic heart disease, wall motion did not discriminate extensive from mild structural damage. 201Tl activity was inversely related to myocardial fibrosis (r = -0.50, p = 0.0001). Severe defects in 201Tl uptake (50%) predicted extensive (30%) fibrosis with 83% sensitivity and 63% specificity. Segmental akinesis and apical location resulted in loss of sensitivity (74% and 58%, respectively). No histologic or wall motion abnormality accounted for poor specificity. In the individual patient, more than nine segments determined viable by imaging criteria predicted left ventricular fibrosis of less than 15% with 86% accuracy.This histopathologic-clinical correlative study supports current evidence of good sensitivity but limited specificity of 201Tl rest-redistribution tomographic imaging in the evaluation of viable myocardium. In the individual patient, more than nine viable segments reliably predicted a limited extension of fibrosis.

Myocardial blood flow (MBF) abnormalities, despite the presence of angiographically normal coronary arteries, have been documented in patients with heart failure due to idiopathic dilated cardiomyopathy (DCM). In particular, a reduction in MBF at rest [1] and/or in response to either metabolic [2] or pharmacologic vasodilating stimuli [3] has been reported. The cause-effect relationship between MBF abnormalities and ventricular dysfunction in DCM, however, is not fully elucidated. An intriguing hypothesis, coming out from the recent recognition of functional abnormalities of the coronary microcirculation in these patients [4–6], points to the relevance of coronary microvascular disease as a primary pathogenetic process leading to progressive ventricular dysfunction. Further testing of this hypothesis implies the demonstration that: 1) in advanced DCM, MBF abnormalities cannot be fully ascribed to the effects of structural and hemodynamic derangement of the myocardium; 2) coronary microvascular dysfunction may be detected also in early stage DCM and may predict progressive deterioration of ventricular function and worse prognosis.

We sought to elucidate the flow-function relation in chronic postischemic dysfunction during vasodilator stress.In patients with ischemia and regional dysfunction, stress echocardiography can elicit three responses in the dysfunctioning segments: no change, improvement or worsening. The physiology underlying these responses is unclear.Seventeen patients with ischemia and left ventricular dysfunction underwent evaluation of regional function by two-dimensional echocardiography and myocardial blood flow by positron emission tomography and 13N-ammonia. Flow (ml/min per g) and function (regional wall motion score [RWMS] from 1 = normal to 4 = dyskinetic) were evaluated both at rest and after dipyridamole (0.56 mg/kg body weight over 4 min).In 45 normal segments, rest to dipyridamole flow increased from 0.83 +/- 0.22 (mean +/- 1 SD) to 1.87 +/- 0.90 (p0.01) with a hyperkinetic contraction pattern. Among dysfunctioning segments, responders (n = 11) showed an upsloping flow-function curve during stress (i.e., increased function [RWMS rest 2.5 +/- 0.5 vs. dipyridamole 1.2 +/- 0.4] and increased flow [rest 0.69 +/- 0.30 vs. dipyridamole 1.89 +/- 1.43, p0.01]); nonresponders (n = 20) had a flat flow-function curve during dipyridamole (i.e., fixed function [RWMS rest and dipyridamole 2.6 +/- 0.5] and no flow increase [rest 0.64 +/- 0.24 vs. dipyridamole 0.87 +/- 0.51, p = NS): Ischemic segments (n = 9) exhibited a downsloping flow-function curve during dipyridamole (i.e., worsened function [RWMS rest 2 +/- 0.5, dipyridamole 3.1 +/- 0.6] and no significant flow change [rest 0.67 +/- 0.29 vs. dipyridamole 0.79 +/- 0.23, p = NS]).Myocardial segments with rest dysfunction and a contractile reserve elicitable by a vasodilator stress more often exhibit residual flow reserve, whereas segments with a fixed or worsening mechanical response during stress show a flat flow response.

The objective of this research was to develop a parallel code for high performance dynamic volume rendering of medical images, starting from 2D image sequences. The availability of a parallel supercomputer enables us to conceive a technological advance in medical imaging, by accounting for the time factor, the fourth dimension (4D), that is, to provide medical specialist dynamic visualization. The parallel system we propose is an SIMD architecture aimed at promoting the potential gains of the use of HPCN technology in medical applications.

Substitution of interstitial tissue by fat may be observed in the right ventricle of hearts but is less common in the left ventricle. Fat was noted in myocardial scars of patients undergoing heart transplantation, prompting this retrospective study to determine the frequency of left ventricular myocardial scar being replaced by fat and its significanceThe left and right ventricles and coronary arteries were sampled systematically and lesions quantified histologically in 97 normal subjects dying accidentally; 116 consecutive failing hearts excised at transplantation from patients with ischemic heart disease, idiopathic dilated cardiomyopathy or chronic valvulopathy; and 34 autopsy hearts of apparently normal subjects with "silent' Chagas' heart disease who died suddenly and unexpectedly. Twenty-two left ventricular aneurysmectomy specimens from ischemic patients with heart failure were also studied. Among excised hearts lipomatous metaplasia of myocardial scar was observed in 68% of ischemic heart disease, in 37% of chronic valvulopathy and in 26% of idiopathic dilated cardiomyopathy patients; it was seen in 15% of Chagasic patients and in 55% of aneurysm walls.Lipomatous metaplasia of scar is often associated with severe heart failure and is more frequent and extensive in ischemic heart disease. Transformation of a compact scar into compressible and "sliding' adipose tissue may worsen ventricular wall function, thus facilitating and/or aggravating aneurysm formation. This phenomenon must be considered in the evaluation of myocardial repair, cardiac imaging of viable myocardium, quantitative morphology of autopsy specimens, and qualitative and quantitative biochemical analysis of myocardial tissue.

s / Journal of Equine Veterinary Science 33 (2013) 321-399 346 Nutrition: Oral Presentations Relating sensory characteristics with biochemical analyses of hays fed to horses S. Julliand , C. Omphalius , M. Orard , O. Parodi , C. Villot , H. Warren , and V. Julliand 4 1 Lab to Field, France, 2 AgroSupDijon, France, 3 Alltech Bioscience Centre, Ireland, 4 Uranie NCA, AgroSup Dijon, France Forages form the basis of horse diets. However in the field, forage nutritive value calculated from biochemical analyses is not commonly used. Horse people evaluate forage quality as “good” or “bad” based on their own quality indicators. The present study aimed at comparing the nutritive value of hays with their sensory characteristics using a descriptive analysis. Twenty hay buyers (equine breeders, trainers, owners and riding school proprietors) were interviewed. While trainers, owners and riding school proprietors said that they looked firstly at the origin of the hay, breeders focused on timing of harvest. All buyers looked at organoleptic qualities as the second major indicator. Among organoleptic qualities, odour and colour were the most frequent indicators mentioned.Twenty-one meadow hays originating from 12 different administrative regions of France were then collected for sensorial and biochemical analyses. For each hay, 2 kg were randomly hand-sampled from one opened bale in 10 different locations. Part was sent for biochemical analysis and part was used for sensorial analysis.The sensorial descriptive analysis was run in three separate workshops with 54 untrained subjects to sort hays by appearance, odour or texture. Subjects were asked to group hays by similarity of view, smell or touch and then to describe the groups with their own qualifying terms (with a maximum of five terms per group).Multidimensional scaling analyses were carried out in order to provide a hierarchical clustering of hays based on their description similarities and to map each group of hays in correlation with the associated description terms. Appearance was separated into four statistically distinct groups and described as “grassy-dark-green”, “mixedthin”, “heterogenic-medium”, “yellow-strawy-moldy”. Odour characteristics were also separated into four groups: “dry-smell of farm-persistent”, “sweet-pleasant”, “spicyaromatic-flowered”, “unpleasant-acid-moldy-smell of urine”. Texture characteristics were separated into three groups: “matted-long-pleasant-soft-homogeneous”, “un -pleasant-strawy”, “mix-short-lightened”.Hay digestible energy (DE) varied from 1.56 to 2.32 Mcal/kg DM and crude protein (CP) from 63 to 163 g/kg DM.The appearance “grassy-dark-green” group had a higher DE than the “yellow-strawy-moldy” group (p

The `oscillations' which have been observed in the visual cortex of cats and monkeys in the case of moving targets are discussed in relation to a temporal coding based on the arrival times of spikes or bursts. A decoding process for this temporal coding is proposed in which neurons work in a correlator mode. In the case of motion analysis, periodic resetting is needed to avoid information jamming. This resetting is proposed to be responsible for the `oscillations'. Good initial synchronization is required for the decoding process to be performed efficiently. A diffusive process based on interdendritic ionic currents is proposed and shown to operate efficiently, without any loss of spatial and temporal resolving powers.

Positron emission tomography (PET) offers the unique capability of measuring specific flow (flow per unit of mass) in man by means of a regional, tridimensional, noninvasive approach. Using PET, myocardial perfusion abnormalities secondary to microvascular disorders have been investigated in arterial hypertension (AH), dilated and hypertrophic cardiomyopathy (CM), as well as in ischemic heart disease (CAD). In AH, regional perfusion at rest is within the normal range, while the coronary reserve and flow response to increase in metabolic demand are blunted. These flow abnormalities are independent of the degree of cardiac hypertrophy and the severity of AH; appropriate anti-ipertensive therapy is able to improve the perfusion abnormalities after long term treatment, independently of the effect on myocardial hypertrophy. Both dilated and hypertrophic CM demonstrate abnormal vasodilating capability, which has been shown to be present in the subclinical form of dilated DM; the reduction of coronary reserve is not related to the presence and extent of the hemodynamic impairment in dilated CM, and involves also nonhypertropied myocardium in asymmetric hypertrophic CM. These findings indicate a primary involvement of coronary microcirculation in non advanced forms of dilated and hypertrophic CM. Finally, in patients with CAD, myocardial territories supplied by angiographically normal coronary arteries show abnormal coronary reserve and flow during pacing tachycardia, indicating that, even in absence of epicardial coronary artery obstruction, microcirculation is impaired in subjects with coronary atherosclerosis. This abnormality can smooth perfusion differences between control and jeopardized regions. Accordingly, the absence of a perfusion defect during stress might indicate the presence of either a non significant stenosis or a diffuse impairment in microcirculatory function. Nuclear perfusion imaging with conventional perfusion tracers does not allow measurements of absolute blood flow, rather it provides an estimation of perfusion inhomogeneities. Although the agreement with the angiographic documentation of coronary artery disease has been frequently considered to characterize the diagnostic reliability of these techniques, the evaluation of myocardial perfusion provides an independent tool for the functional assessment of patient with heart disease. The possibility to obtain measurements of regional myocardial blood flow, provided by positron emission tomography, helps to identify the mechanisms affecting flow regulation in the myocardium. This tool thus provides a new rationale for the application of perfusion imaging, to obtain a more precise characterization of these patients, beyond the agreement with the morphological angiographic picture.

The natural history of idiopathic dilated cardiomyopathy (IDC), once a disease with a dire prognosis, is thought to be changing. Aim of this study was to describe the clinical characteristics, long term course and prognostic factors of IDC patients followed up prospectively since the late eighties.Patients with a diagnosis of IDC confirmed by normal coronary angiography, non specific endomyocardial biopsy findings and a left ventricular ejection fraction below 50% were consecutively enrolled in a multicenter registry and followed up at 6-months intervals.From January 1986 till January 1994, 441 IDC patients with a mean age of 43 +/- 13 years (range 8-68) entered the registry. Thirty per cent of patients were women and 8% had familial dilated cardiomyopathy. NYHA class was I-II in 77% and 35% of patients were asymptomatic at the time of diagnosis. Treatment included digitalis in 235 patients (53%), diuretics in 239 (54%), angiotensin converting enzyme inhibitors in 269 (61%), betablockers in 108 (24%). Chronic atrial fibrillation was detected in 10% of patients and left bundle branch block in 24%. Mean cardiothoracic ratio was 0.54 +/- 0.06. Mean left ventricular end diastolic dimension was 38 +/- 6 mm/m2; 48% of patients had minimal or mild left ventricular dilatation. Mean left ventricular ejection fraction was 30 +/- 10%. At Holter monitoring 67% of cases had complex ventricular arrhythmias, 37% had ventricular tachycardia and 4% had advanced atrioventricular block. Mean exercise stress test duration was 9 +/- 4 minutes. After a mean follow up of 31 +/- 24 months, 337 patients were alive without transplantation and 5 were lost to follow up; 60 patients (14%) had died of cardiac causes, namely heart failure (6%), sudden death (7%) and pulmonary embolism (1%) and 30 had been transplanted (7%), while 4 had died of unclear causes. Survival and transplant-free survival were 94% and 90% at 2 years and 82 and 76% at 5 years, respectively. At multivariate analysis pulmonary capillary wedge pressure (p = 0.0001, odds ratio, for values15 mm Hg, 2.05) and betablocker treatment (p = 0.002, odds ratio 0.26) were independent predictors of survival.In this large, multicenter prospective study, prognosis of IDC in the eighties appears to be improved. Early diagnosis, together with improved medical treatment, probably bears a causal relation to these changes.

The recent introduction of new tracers and stressors has increased the number of combinations of techniques that can be used for the diagnostic and prognostic stratification of patients with coronary artery disease. However, these new techniques still need to be standardized for clinical use. Thallium-201 scintigraphy is at present the most common method to assess transient ischemia and viability in patients. Dynamic exercise and dipyridamole show similar incidence of major cardiac complications and their use can be considered sufficiently safe. Further experimental and multicenter clinical studies are needed for 99mTc-Sestamibi and 99mTc-Teboroxime and for new stressors such as adenosine and dobutamine.

The failure of non-imaging techniques in identifying viable segments has favoured the clinical application of nuclear imaging. The main pathways that support radionuclide imaging are cell membrane integrity, persistence of intermediary metabolism and demonstration of a residual coronary reserve. Thallium-201 reinjection or rest protocols allow the identification of viable myocardium in most of patients with wall motion abnormalities and appear to be the most diffuse, low-cost and available method to detect viable myocardium. More complex approaches use positron emission tomography and matched flow/metabolic information. Flow/metabolic "mismatch" usually identifies most of hypoperfused regions that show post-operative improvement of regional wall motion. The last promising approach is represented by the demonstration of a maintained regional coronary reserve in dyssynergic areas. 99mTc-microspheres (or Teboroxime in the future) can be successfully used for this purpose. The clinical application of radionuclides appears to be one of the principal imaging tools able to identify residual viability.

To assess whether myocardial stunning occurs following brief episodes of effort ischemia, ventricular function was assessed by radionuclide angiography in 29 patients with coronary artery disease. No patient had evidence of previous myocardial infarction. Patients were divided into two groups according to presence of single (14 patients, Group 1) or multi-vessel (15 patients, Group 2) coronary artery disease. Equilibrium radionuclide angiocardiography was performed in the left anterior oblique projection by a small field-of-view gamma-camera. Acquisition were performed at baseline, at peak exercise, then again at 1 and 5 minutes of the recovery phase. For each acquisition, ejection fraction, peak filling rate and wall motion index were measured and compared. No difference in baseline and stress measurements was found between Group 1 and Group 2, except for the wall motion index that was more impaired during ischemia in patients of Group 2. Global and regional indexes of ventricular function did not show significant differences also in the two recovery periods when compared to the relative baseline values. Transient ischemia caused by an increase of oxygen demand did not reproduce the phenomenon of systolic and diastolic stunning observed in animal experiments, although in all patients the ischemia was of sufficient duration and severity to induce transient ventricular dysfunction.

The relationship between radioisotopic, echocardiographic, and angiographic markers of myocardial viability is still to be defined. To this purpose, 14 patients with previous myocardial infarction were studied using a multiparametric approach. Each patient underwent, on separate days, rest thallium 201 and technetium 99m Sestamibi planar scintigraphy, dobutamine/dipyridamole stress echocardiography, and coronary angiography; 11 of these patients underwent also dipyridamole echocardiographic testing. Thallium 201 and Sestamibi uptakes at rest were expressed as percentage of maximal activity in each projection using a 13 segment model. Dobutamine and dipyridamole stress echocardiography were analyzed using a score index ranging from 1 (normokinesis) to 4 (dyskinesis) and a similar segmentation. Coronary angiography was analyzed by quantitative approach. In all patients, follow-up echocardiography was performed following coronary revascularization. Before revascularization, 75 segments showed regional dyssynergies. Thallium 201 showed the highest sensitivity and specificity in the preoperative identification of viability, whereas Sestamibi was affected by a significant number of false-negative studies. Among echocardiographic techniques, dobutamine was slightly superior to dipyridamole in the detection of viable segments. The degree of coronary stenosis failed to predict the recovery of function following by-pass graft or angioplasty in almost all segments; however, in case of occlusion, most viable segments were perfused by adequately collateralized coronary arteries.