Blockade of Store-Operated Calcium Entry Reduces IL-17/TNF Cytokine-Induced Inflammatory Response in Human Myoblasts

Muscle inflammation as in idiopathic inflammatory myopathies (IIM) leads to muscle weakness, mononuclear cell infiltration, and myofiber dysfunction affecting calcium channels. The effects of interleukin-17A (IL-17) and tumor necrosis factor-α (TNFα) on inflammation and calcium changes were investigated in human myoblasts. Human myoblasts were exposed to IL-17 and/or TNFα with/without store-operated Ca2+ entry (SOCE) inhibitors (2-ABP or BTP2). For co-cultures, peripheral blood mononuclear cells (PBMC) from healthy donors activated or not with phytohemagglutinin (PHA) were added to myoblasts at a 5:1 ratio. IL-17 and TNFα induced in synergy CCL20 and IL-6 production by myoblasts (>14-fold). PBMC-myoblast co-cultures enhanced CCL20 and IL-6 production in the presence or not of PHA compared to PBMC or myoblast monocultures. Anti-IL-17 and/or anti-TNFα decreased the production of IL-6 in co-cultures (p < 0.05). Transwell system that prevents direct cell-cell contact reduced CCL20 (p < 0.01) but not IL-6 secretion. IL-17 and/or TNFα increased the level of the ER stress marker Grp78, mitochondrial ROS and promoted SOCE activation by 2-fold (p < 0.01) in isolated myoblasts. SOCE inhibitors reduced the IL-6 production induced by IL-17/TNFα. Therefore, muscle inflammation induced by IL-17 and/or TNFα may increase muscle cell dysfunction, which, in turn, increased inflammation. Such close interplay between immune and non-immune mechanisms may drive and increase muscle inflammation and weakness

Preventing acute decrease in renal function induced by coronary angiography (PRECORD): a prospective randomized trial

SummaryBackgroundInfusion of saline attenuates the decrease in renal function induced by radiographic contrast agents among patients with chronic renal insufficiency.AimThe Preventing Renal alteration in Coronary Disease (PRECORD) trial was a randomized trial to assess the effect on renal function of saline infusion during and after coronary angiography in 201 patients without severe chronic renal insufficiency (serum creatinine<140μmol/L).MethodsAll patients received standard oral hydration: 2000mL of tap water within the 24hours after coronary angiography. Patients were randomized before the procedure to intravenous hydration (1000mL of 0.9% saline infusion) or no additional hydration. The infusion was started in the catheterization laboratory and continued for 24hours. The primary endpoint was the change in calculated creatinine clearance between baseline and 24hours after coronary angiography. The same ionic low osmolar radiographic contrast agent (ioxaglate) was used in all patients.ResultsBoth groups had similar baseline characteristics, including age, serum creatinine, volume of contrast and proportion of patients undergoing ad hoc coronary angioplasty. The overall decrease in serum creatinine clearance 24hours after the procedure was –3.44 (0.68)mL/min. The change in serum creatinine clearance 24hours after the procedure was –2.81 (1.07)mL/min in the infusion group vs –4.09 (0.91)mL/min in the control group (p=0.38).ConclusionRenal function is altered only slightly 24hours after coronary angiography with standard oral hydration alone and is not affected by saline infusion started at the beginning of coronary angiography, even in patients with mild-to-moderate renal dysfunction

Cardioprotective effects of shock wave therapy: A cardiac magnetic resonance imaging study on acute ischemia-reperfusion injury

IntroductionCardioprotection strategies remain a new frontier in treating acute myocardial infarction (AMI), aiming at further protect the myocardium from the ischemia-reperfusion damage. Therefore, we aimed at investigating the mechano-transduction effects induced by shock waves (SW) therapy at time of the ischemia reperfusion as a non-invasive cardioprotective innovative approach to trigger healing molecular mechanisms.MethodsWe evaluated the SW therapy effects in an open-chest pig ischemia-reperfusion (IR) model, with quantitative cardiac Magnetic Resonance (MR) imaging performed along the experiments at multiple time points (baseline (B), during ischemia (I), at early reperfusion (ER) (∼15 min), and late reperfusion (LR) (3 h)). AMI was obtained by a left anterior artery temporary occlusion (50 min) in 18 pigs (32 ± 1.9 kg) randomized into SW therapy and control groups. In the SW therapy group, treatment was started at the end of the ischemia period and extended during early reperfusion (600 + 1,200 shots @0.09 J/mm2, f = 5 Hz). The MR protocol included at all time points LV global function assessment, regional strain quantification, native T1 and T2 parametric mapping. Then, after contrast injection (gadolinium), we obtained late gadolinium imaging and extra-cellular volume (ECV) mapping. Before animal sacrifice, Evans blue dye was administrated after re-occlusion for area-at-risk sizing.ResultsDuring ischemia, LVEF decreased in both groups (25 ± 4.8% in controls (p = 0.031), 31.6 ± 3.2% in SW (p = 0.02). After reperfusion, left ventricular ejection fraction (LVEF) remained significantly decreased in controls (39.9 ± 4% at LR vs. 60 ± 5% at baseline (p = 0.02). In the SW group, LVEF increased quickly ER (43.7 ± 11.4% vs. 52.4 ± 8.2%), and further improved at LR (49.4 ± 10.1) (ER vs. LR p = 0.05), close to baseline reference (LR vs. B p = 0.92). Furthermore, there was no significant difference in myocardial relaxation time (i.e. edema) after reperfusion in the intervention group compared to the control group: ΔT1 (MI vs. remote) was increased by 23.2±% for SW vs. +25.2% for the controls, while ΔT2 (MI vs. remote) increased by +24.9% for SW vs. +21.7% for the control group.DiscussionIn conclusion, we showed in an ischemia-reperfusion open-chest swine model that SW therapy, when applied near the relief of 50′ LAD occlusion, led to a nearly immediate cardioprotective effect translating to a reduction in the acute ischemia-reperfusion lesion size and to a significant LV function improvement. These new and promising results related to the multi-targeted effects of SW therapy in IR injury need to be confirmed by further in-vivo studies in close chest models with longitudinal follow-up

929-63 Dobutamine Stress Cine Magnetic Resonance Imaging versus PET for Detection of Myocardial Viability

To identify viable myocardium before coronary revascularization, we prospectively submitted eleven patients (60±7 yrs; 11 M) with previous Q-wave myocardial infarction to 18FDG-Positon Emission Tomography and low-dose (5 to 10 μg/kg/min) dobutamine cine-MRI. 18FDG uptake &gt; 60% was considered indicative of viable tissue. Ouantitation of systolic wall thickening/thinning (SW) was performed by use of a computer software allowing automatic detection of epicardial and endocardial outlines, at rest and under 5, 7.5 and 10 μg/kg/min of dobutamine. Heart slices of both 18FDG-PET scans and dobutamine cine-MRI were divided in 8 segments, matched and analyzed byobservers blinded to clinical data. Sixty-five segments were considered viable by 18FDG-PET; in this subgroup, rest SW thickening averaged 47±5% and improved by 43±8% under low-dose dobutamine. In the remaining 23 segments considered non viable by PET. rest SW thickening averaged 14±7%*(*p&lt;0.05 vs viable segment group) and further worsened by –13±8%*during low-dose dobutamine stress (*p&lt;0.05 versus viable segment group). Positive predictive value of low-dose dobutamine stress cine-MRI for assessment of myocardial viability was 84%. These data suggest that quantitative assessment of regional wall motion by dobutamine cine-MRI may help discriminate viable from non viable myocardium as defined by 18FDG-Positon Emission Tomography

Early detection of myocardial fibrosis in type II diabetic patients using MR T1-mapping

ORAL PRESENTATIONInternational audienc

Determination of the myocardial area at risk after reperfused acute myocardial infarction with different imaging techniques: cardiac magnetic resonance imaging, multidetector computed tomography and histopathological validation

International audiencen.

Myocardial T1-mapping for early detection of left ventricular myocardial fibrosis in systemic sclerosis

International audiencen.

Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction : trials and tribulations

Altres ajuts: D.J.H. and D.M.Y. are funded by the British Heart Foundation and the Rosetrees Trust, and are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre of which D.M.Y. is a senior investigator. G.H. is supported by the German Research Foundation (He 1320/18-3; SFB 1116 B8)

Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction: trials and tribulations

D.J.H. and D.M.Y. are funded by the British Heart Foundation and the Rosetrees Trust, and are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre of which D.M.Y. is a senior investigator. D.G.-D. is funded by the Cardiovascular Research Network of the Spanish Institute of Health Instituto de Salud Carlos III (ISCiii RETICS-RIC, RD12/0042/0021). G.H. is supported by the German Research Foundation (He 1320/18-3; SFB 1116 B8). B.I. is funded by the Carlos III Institute of Health and European Regional Development Fund (ERDF/FEDER) (PI13/01979), and the ISCiii Cardiovascular Research Network (RD12/0042/0054). Funding to pay the Open Access publication charges for this article was provided by Red de Investigacion Cardiovascular del Instituto de Salud Carlos III, grupo Hospital Universitari Vall d'Hebron (RETICS 2012 RD12/0042/0021).S