169 Does atrial differences in endothelium damage, leukocyte and platelet activation contribute to chamber specific thrombogenic status in patients with atrial fibrillation?

BackgroundIn atrial fibrillation (AF), the reasons why most of the thrombi form in the left atrium are mainly unknown. In the vasculature, endothelial damage together with platelet activation and inflammation contribute to initiation of blood coagulation and thrombus growth.ObjectiveThe purpose of this study was to investigate whether atrial-specific differences in endothelial damage, leukocyte activation, platelet stimulation occur in patients with AF.MethodsTwenty patients (15 men, 5 women; age 55±8 years, 15 paroxystic AF, 5 persistent AF) with AF undergoing ablation were investigated. Blood samples from the left and right atrium were obtained at the start of the procedure. Procoagulant microparticles (MPs), reliable markers of vascular damage were measured by capture assays. Their procoagulant abilities were quantified by functional prothrombinase assay and their cellular origin were determined (endothelium, platelet, leukocyte). In addition, platelet reactivity was evaluated by whole blood flow cytometry for expression of platelet Pselectin (CD62P), active glycoprotein IIbIIIa receptor (PAC-1). Platelet aggregation was evaluated using Arachidonic acid (AA), ADP, TRAP and collageninduced whole blood aggregometry.ResultsNo atrial-specific differences in the levels of total procoagulant MP, leukocyte-derived-MP and platelet-derived MP could be evidenced. Conversely, endothelial-derived MPs (CD105+) were slightly elevated in the right atrium (RA 0.96±0.53 vs. LA 0.80±0.45nm PhtdSer Eq.; p=0.041). Likewise, collagen-induced platelet aggregation was evidenced in the right atrium (Collagen 1mg/l RA: 48±33% vs LA 37±29%; p 0.035; collagen 2,5mg/l RA: 76±25% vs LA: 60±29%; p=0.001).ConclusionsIn patients with AF, endothelial damage and collageninduced platelet aggregation appear slightly more pronounced in the right atrium. Our data did not substantiate the view that chamber specific enhanced thrombogenic status could be a reliable explanation for the increased propensity for thrombus formation observed in the left atrium in AF patients

Echocardiography underestimates stroke volume and aortic valve area:implications for patients with small-area low-gradient aortic stenosis

AbstractBackgroundDiscordance between small aortic valve area (AVA; < 1.0 cm2) and low mean pressure gradient (MPG; < 40 mm Hg) affects a third of patients with moderate or severe aortic stenosis (AS). We hypothesized that this is largely due to inaccurate echocardiographic measurements of the left ventricular outflow tract area (LVOTarea) and stroke volume alongside inconsistencies in recommended thresholds.MethodsOne hundred thirty-three patients with mild to severe AS and 33 control individuals underwent comprehensive echocardiography and cardiovascular magnetic resonance imaging (MRI). Stroke volume and LVOTarea were calculated using echocardiography and MRI, and the effects on AVA estimation were assessed. The relationship between AVA and MPG measurements was then modelled with nonlinear regression and consistent thresholds for these parameters calculated. Finally the effect of these modified AVA measurements and novel thresholds on the number of patients with small-area low-gradient AS was investigated.ResultsCompared with MRI, echocardiography underestimated LVOTarea (n = 40; −0.7 cm2; 95% confidence interval [CI], −2.6 to 1.3), stroke volumes (−6.5 mL/m2; 95% CI, −28.9 to 16.0) and consequently, AVA (−0.23 cm2; 95% CI, −1.01 to 0.59). Moreover, an AVA of 1.0 cm2 corresponded to MPG of 24 mm Hg based on echocardiographic measurements and 37 mm Hg after correction with MRI-derived stroke volumes. Based on conventional measures, 56 patients had discordant small-area low-gradient AS. Using MRI-derived stroke volumes and the revised thresholds, a 48% reduction in discordance was observed (n = 29).ConclusionsEchocardiography underestimated LVOTarea, stroke volume, and therefore AVA, compared with MRI. The thresholds based on current guidelines were also inconsistent. In combination, these factors explain > 40% of patients with discordant small-area low-gradient AS

Thermal and nuclear design review of the NRX-A5 Reactor

A thermal and nuclear NRX-A5 Design Review was held at WANL on April 10, 1964. Analyses and planning performed to date on the NRX-A5 and subsequent reactors were presented. Systems analyses were performed on various "cooled periphery".and "hot periphery" seal configurations. A number of inner reflector designs were examined, as well as means for cooling the lateral support springs. Core component redesign incl,uded methods for controlling inter-element pressure distribution by undercutting or chamfering of fuel elements. Changes in tie rod diameters, use of as-extruded fuel elements, and performance analysis of the various systems were also described. Nuclear analysis was confined to parametric studies on excess reactivity and control drum span for inner reflector material combinations of graphite, aluminum, and/or beryllium. Changes required to more precisely define the NRX-A5 were discussed together with the effects associated with the twice power reactor capability envisioned for subsequent reactors

Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays

Aims Several high-sensitivity cardiac troponin (hs-cTn) assays have recently been developed. It is unknown which hs-cTn provides the most accurate prognostic information and to what extent early changes in hs-cTn predict mortality. Methods and results In a prospective, international multicentre study, cTn was simultaneously measured with three novel [high-sensitivity cardiac Troponin T (hs-cTnT), Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI, Siemens] and a conventional assay (cTnT, Roche Diagnostics) in a blinded fashion in 1117 unselected patients with acute chest pain. Patients were followed up 2 years regarding mortality. Eighty-two (7.3%) patients died during the follow-up. The 2-year prognostic accuracy of hs-cTn was most accurate for hs-cTnT [area under the receivers operating characteristic curve (AUC) 0.78 (95% CI: 0.73-0.83) and outperformed both hs-cTnI (Beckman-Coulter, 0.71 (95% CI: 0.65-0.77; P = 0.001 for comparison), hs-cTnI (Siemens) 0.70 (95% CI: 0.64-0.76; P < 0.001 for comparison)] and cTnT 0.67 (95% CI: 0.61-0.74; P < 0.001 for comparison). Absolute changes of hs-cTnT were more accurate than relative changes in predicting mortality, but inferior to presentation values of hs-cTnT. Combining changes of hs-cTnT within the first 6 h with their presentation values did not further improve prognostic accuracy. Similar results were obtained for both hs-cTnI assays regarding the incremental value of changes. Hs-cTn concentrations remained predictors of death in clinically challenging subgroups such as patients with pre-existing coronary artery disease, impaired renal function, and patients older than 75 years. Conclusion High-sensitivity cardiac Troponin T is more accurate than hs-cTnI in the prediction of long-term mortality. Changes of hs-cTn do not seem to further improve risk stratification beyond initial presentation value

Modified Continuity Equation Using Left Ventricular Outflow Tract Three-Dimensional Imaging for Aortic Valve Area Estimation

PURPOSE: Aortic valve area (AVA) is usually estimated by the continuity equation (CE) in which the left ventricular outflow tract (LVOT) area is calculated assuming a circular shape. This study aimed to compare measurements of LVOT area using standard 2D transthoracic echocardiography (2DTTE), 3D transesophageal echocardiography (3DTEE), and multidetector computed tomography (MDCT) and assess their relative impact on AVA estimated by the CE. METHODS AND RESULTS: We prospectively enrolled 60 patients with severe aortic stenosis (AS) referred for transcatheter aortic valve replacement (TAVR) who systematically underwent 2DTTE, 3DTEE, and MDCT. Mean LVOT areas obtained by 2DTTE (3.28±0.66 cm2 ) and 3DTEE (3.95±0.90 cm2 ) were significantly underestimated when compared to the mean MDCT LVOT area (4.31±0.99 cm2 ). LVOT was rather elliptical than round, with a mean eccentricity index of 1.47 (ratio of maximum to minimum LVOT diameters) assessed by MDCT. Mean TTE AVA estimated by the CE was 0.62±0.20 cm2 . Substitution of 2DTTE LVOT area by 3DTEE LVOT area in the CE resulted in AVA of 0.74±0.24 cm2 , while using MDCT LVOT area held an AVA of 0.80±0.24 cm2 . MDCT-derived AVA was similar to MDCT planimetric AVA and allowed 24% of patients to be reclassified from severe to moderate AS. CONCLUSIONS: 2DTTE and 3DTEE underestimate LVOT area when compared to MDCT with significant impact on AVA estimation. Assessment through MDCT fusion AVA may be of incremental value in patients with discrepant severity criteria for AS.info:eu-repo/semantics/publishedVersio

Scientific Statement: Socioecological Determinants of Prediabetes and Type 2 Diabetes

In this article, we examine the socioecological determinants--the biological, geographic, and built environment factors--that influence risk for prediabetes and type 2 diabetes. A socioecological perspective looks beyond the individual to evaluate a multitude of influences, from the surrounding home, work, school, and community environments to social determinants and the influence of public policy on individual behavior (1). Figure 1, adapted from the Institute of Medicine socioecological model of childhood obesity, provides a good framework for understanding potential socioecological determinants of risk for type 2 diabetes. In November 2012, the American Diabetes Association Prevention Committee convened a writing group to review the evidence on socioecological factors contributing to recent increases in prediabetes and type 2 diabetes. Drawing from the work of the committee, in this article we review the overarching evidence-based contributions of socioecological factors to risk for type 2 diabetes. Rather than incorporate the entire universe of relational observations, this scientific statement is intended to evaluate the extent to which data indicate a contributing role of social and environmental factors to the current epidemic of type 2 diabetes

Morphine induces preconditioning via activation of mitochondrial KCa channels

PURPOSE: Mitochondrial calcium sensitive potassium (mK(Ca)) channels are involved in cardioprotection induced by ischemic preconditioning. In the present study we investigated whether morphine-induced preconditioning also involves activation of mK(Ca) channels. METHODS: Isolated rat hearts (six groups; each n = 8) underwent global ischemia for 30 min followed by a 60-min reperfusion. Control animals were not further treated. Morphine preconditioning (MPC) was initiated by two five-minute cycles of morphine 1 muM infusion with one five-minute washout and one final ten-minute washout period before ischemia. The mK(Ca) blocker, paxilline 1 muM, was administered, with and without morphine administration (MPC + Pax and Pax). As a positive control, we added an ischemic preconditioning group (IPC) alone and combined with paxilline (IPC + Pax). At the end of reperfusion, infarct sizes were determined by triphenyltetrazoliumchloride staining. RESULTS: Infarct size was (mean +/- SD) 45 +/- 9% of the area at risk in the Control group. The infarct size was less in the morphine or ischemic preconditioning groups (MPC: 23 +/- 8%, IPC: 20 +/- 5%; each P < 0.05 vs Control). Infarct size reduction was abolished by paxilline (MPC + Pax: 37 +/- 7%, P < 0.05 vs MPC and IPC + Pax: 36 +/- 6%, P < 0.05 vs IPC), whereas paxilline alone had no effect (Pax: 46 +/- 7%, not significantly different from Control). CONCLUSION: Cardioprotection by morphine-induced preconditioning is mediated by activation of mK(Ca) channel