BackgroundAggregates formed between leukocytes and platelets in the circulation lead to release of tissue factor (TF)–bearing microparticles contributing to a prothrombotic state. As enterohemorrhagic Escherichia coli (EHEC) may cause hemolytic uremic syndrome (HUS), in which microthrombi cause tissue damage, this study investigated whether the interaction between blood cells and EHEC virulence factors Shiga toxin (Stx) and lipopolysaccharide (LPS) led to release of TF.Methodology/Principal FindingsThe interaction between Stx or LPS and blood cells induced platelet-leukocyte aggregate formation and tissue factor (TF) release, as detected by flow cytometry in whole blood. O157LPS was more potent than other LPS serotypes. Aggregates formed mainly between monocytes and platelets and less so between neutrophils and platelets. Stimulated blood cells in complex expressed activation markers, and microparticles were released. Microparticles originated mainly from platelets and monocytes and expressed TF. TF–expressing microparticles, and functional TF in plasma, increased when blood cells were simultaneously exposed to the EHEC virulence factors and high shear stress. Stx and LPS in combination had a more pronounced effect on platelet-monocyte aggregate formation, and TF expression on these aggregates, than each virulence factor alone. Whole blood and plasma from HUS patients (n = 4) were analyzed. All patients had an increase in leukocyte-platelet aggregates, mainly between monocytes and platelets, on which TF was expressed during the acute phase of disease. Patients also exhibited an increase in microparticles, mainly originating from platelets and monocytes, bearing surface-bound TF, and functional TF was detected in their plasma. Blood cell aggregates, microparticles, and TF decreased upon recovery.Conclusions/SignificanceBy triggering TF release in the circulation, Stx and LPS can induce a prothrombotic state contributing to the pathogenesis of HUS.

Hemodynamic force analysis has been proposed as a novel tool for early detection of subclinical systolic dysfunction in heart failure with preserved ejection fraction (HFpEF). Here we investigated the ability of hemodynamic forces to discriminate between healthy subjects and heart failure patients with varying degrees of systolic dysfunction. We studied 34 controls, 16 HFpEF patients, and 25 heart failure patients with mid-range (HFmrEF) or reduced ejection fraction (HFrEF) using cardiac magnetic resonance with acquisition of cine images and 4D flow at 1.5 T. The Navier–Stokes equation was used to compute global left ventricular hemodynamic forces over the entire cardiac cycle. Forces were analyzed for systole, diastole, and the entire heartbeat, with and without normalization to left ventricular volume. Volume-normalized hemodynamic forces demonstrated significant positive correlation with EF (r2 = 0.47, p < 0.0001) and were found significantly lower in heart failure with reduced ejection fraction compared to controls (p < 0.0001 for systole and diastole). No difference was seen between controls and HFpEF (p > 0.34). Non-normalized forces displayed no differences between controls and HFpEF (p > 0.24 for all analyses) and did not correlate with EF (p = 0.36). Left ventricular hemodynamic force analysis, whether indexed to LV volumes or not, is not ready for clinical trials on HFpEF assessment.

Background Increased pulmonary blood volume (PBV) is a measure of congestion and is associated with an increased risk of cardiovascular events. PBV can be quantified using cardiovascular magnetic resonance (CMR) imaging as the product of cardiac output and pulmonary transit time (PTT), the latter measured from the contrast time-intensity curves in the right and left side of the heart from first-pass perfusion (FPP). Several methods of estimating PTT exist, including pulmonary transit beats (PTB), peak-to-peak, and center of gravity (CoG). The aim of this study was to determine the accuracy and precision for these methods of quantifying the PBV, taking the left atrium volume (LAV) into consideration. Methods Fifty-eight participants (64 ± 11 years, 24 women) underwent 1.5 T CMR. PTT was quantified from (1) a basal left ventricular short-axis image (FPP), and (2) the reference method with a separate contrast administration using an image intersecting the pulmonary artery (PA) and the LA (CoG(PA-LA)). Results Compared to the reference, PBV for (a) PTB(FPP) was 14 ± 17% larger, (b) peak-peak(FPP) was 17 ± 16% larger, and (c) CoG(FPP) was 18 ± 10% larger. Subtraction of the LAV (available for n = 50) decreased overall differences to − 1 ± 19%, 2 ± 18%, and 3 ± 12% for PTB(FPP), peak-peak(FPP), and CoG(FPP), respectively. Lowest interobserver variability was seen for CoG(FPP) (− 2 ± 7%). Conclusions CoG(PA-LA) and FPP methods measured the same PBV only when adjusting for the LAV, since FPP inherently quantifies a volume consisting of PBV + LAV. CoG(FPP) had the best precision and lowest interobserver variability among the FPP methods of measuring PBV. Graphical abstract