Serial Changes in Plasma Levels of Cytokines in Patients with Coronary Artery Disease

Roberto H Heinisch1, Carlos R Zanetti1, Fabiano Comin1, Juliano L Fernandes2, José A Ramires2, Carlos V Serrano Jr21Federal University of Santa Catarina, Florianópolis, Brazil; 2Heart Institute (InCor), University of São Paulo Medical School, São Paulo, BrazilObjectives: Inflammation is known to be a major determinant of the progression of coronary artery disease (CAD). In the present study we have evaluated the plasma levels of cytokines – tumor necrosis factor-α (TNF), interleukin-1α (IL-1), interleukin-6 (IL-6), interferon-γ (IFN), and interleukin-10 (IL-10) – to examine the association between these cytokines and C-reactive protein (CRP) in patients with CAD.Methods: Patients with acute coronary syndromes (ACS; n = 20) were compared with patients with stable angina (SA; n = 20) and with control volunteers (C; n = 20). Blood samples were collected at the time of admission from all patients and 15 and 30 days thereafter.Results: CRP levels (20.8 ± 8.8 mg/L) (mean ± SEM) were higher at baseline in ACS than SA patients (4.1 ± 0.8 mg/L) or the control subjects (5.1 ± 1.8 mg/L) (p < 0.05). At admission, IL-6 was detected in 50% of the ACS patients and 5% of the SA patients or control subjects, while TNF was detected in 35% of the ACS and SA patients but only in 5% of control subjects. Subsequently, IL-6 levels declined and were no longer detectable, while TNF levels increased among ACS patients at all time periods tested when compared with other patients. The presence of IL-1 and IL-10 were not detectable in the blood samples examined, and IFN could only be detected in the ACS group. A significant correlation was observed between IL-6 and CRP levels (r = 0.4; p < 0.01) in all groups. There were no correlations among any of the other cytokines and CRP levels.Conclusions: Our study demonstrates raised levels of TNF, IL6, IFN, and CRP in patients with ACS and a positive correlation between IL6 and CRP but not with the other cytokines. Keywords: cytokines, tumor necrosis factor-α, interleukin-6, C-reactive protein, coronary artery diseas

Preliminary assessment of cardiac short term safety and efficacy of manganese chloride for cardiovascular magnetic resonance in humans

<p>Abstract</p> <p>Background</p> <p>Manganese based agents are intracellular and accumulate inside myocytes allowing for different imaging strategies compared to gadolinium contrasts. While previous agents release manganese very slowly in the circulation, MnCl₂allows for rapid Mn2⁺uptake in myocytes, creating a memory effect that can be potentially explored. Data on animal models are very encouraging but the safety and efficacy of this approach in humans has not yet been investigated. Therefore, our objectives were to study the safety and efficacy of a rapid infusion of manganese chloride (MnCl₂) for cardiovascular magnetic resonance (CMR) in humans.</p> <p>Methods</p> <p>Fifteen healthy volunteers underwent a CMR scan on a 1.5 T scanner. Before the infusion, cardiac function was calculated and images of a short axis mid-ventricular slice were obtained using a 2D and 3D gradient-echo inversion recovery (GRE-IR) sequence, a phase-sensitive IR sequence and a single breath-hold segmented IR prepared steady-state precession acquisition for T₁calculations. MnCl₂was infused over three minutes at a total dose of 5 μMol/kg. Immediately after the infusion, and at 15 and 30 minutes later, new images were obtained and cardiac function re-evaluated.</p> <p>Results</p> <p>There was a significant decrease in T₁values compared to baseline, sustained up to 30 minutes after the MnCl₂infusion (pre,839 ± 281 ms; 0 min, 684 ± 99; 15 min, 714 ± 168; 30 min, 706 ± 172, P = 0.003). The 2D and 3D GRE-IR sequence showed the greatest increase in signal-to-noise ratio compared to the other sequences (baseline 6.6 ± 4.2 and 9.7 ± 5.3; 0 min, 11.3 ± 4.1 and 15.0 ± 8.7; 15 min, 10.8 ± 4.0 and 16.9 ± 10.2; 30 min, 10.6 ± 5.2 and 16.5 ± 8.3, P < 0.001 for both). There was a slight increase in systolic pressure and heart rate after three and four minutes of the infusion with normalization of these parameters thereafter. Patients showed good tolerance to MnCl₂with no major adverse events, despite all reporting transient facial flush.</p> <p>Conclusions</p> <p>In the short term, MnCl₂appears safe for human use. It effectively decreases myocardium T₁, maintaining this effect for a relatively long period of time and allowing for the development of new imaging strategies in CMR, especially in ischemia research.</p

Escore prognóstico precoce após 15 minutos do tratamento da asma aguda na sala de emergência

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Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin

Background: In the setting of stable coronary artery disease (CAD), it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alone. Objective: We sought to compare the anti-inflammatory and antiplatelet effects of ezetimibe 10 mg/simvastatin 20 mg (E10/S20) with simvastatin 80 mg (S80). Methods and results: CAD patients (n = 83, 63 +/- 9 years, 57% men) receiving S20, were randomly allocated to receive E10/S20 or S80, for 6 weeks. Lipids, inflammatory markers (C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, soluble CD40 ligand and oxidized LDL), and platelet aggregation (platelet function analyzer [PFA]-100) changes were determined. Baseline lipids, inflammatory markers and PFA-100 were similar between groups. After treatment, E10/S20 and S80 patients presented, respectively: (1) similar reduction in LDL-C (29 +/- 13% vs. 28 +/- 30%, p = 0.46), apo-B (18 +/- 17% vs. 22 +/- 15%, p = 0.22) and oxidized LDL (15 +/- 33% vs. 18 +/- 47%, p = 0.30); (2) no changes in inflammatory markers; and, (3) a higher increase of the PFA-100 with E10/S20 than with S80 (27 +/- 43% vs. 8 +/- 33%, p = 0.02). Conclusions: These data suggest that among stable CAD patients treated with S20, (1) both E10/S20 and S80 were equally effective in further reducing LDL-C; (2) neither treatment had any further significant anti-inflammatory effects; and (3) E10/S20 was more effective than S80 in inhibiting platelet aggregation. Thus, despite similar lipid lowering and doses 4x less of simvastatin, E10/S20 induced a greater platelet inhibitory effect than S80. (C) 2011 Elsevier Ireland Ltd. All rights reserved.Astra ZenecaAstraZenecaMerck/Schering PloughMerck/Schering PloughPfizerPfizerSao Paulo Research FoundationSao Paulo Research Foundation [FAPESP/05/57710-3