Interleukin-6, infection and cardiovascular outcomes in acute heart failure: Findings from the EDIFICA registry.

AIMS: Interleukin-6 (IL-6) is upregulated in response to infectious and inflammatory triggers and independently predicts all-cause mortality in acute heart failure (AHF). However, the association of IL-6 with cardiovascular outcomes and its interplay with C-reactive protein and infection, a major precipitating factor in AHF, remains poorly understood. METHODS AND RESULTS: The association between IL-6 and clinical outcomes (180 days) in AHF was evaluated using a cohort of 164 patients from the EDIFICA registry. Median IL-6 levels at admission were 17.4 pg/mL. Patients in the higher admission IL-6 tertile presented with lower blood pressure and more congestion, were diagnosed more frequently with infection, and had a longer hospital stay. Higher IL-6 levels were associated with increased risk of HF rehospitalization (hazard ratio per log2 3.69, 95% confidence interval (CI) 1.26-10.8, p =.017) and the composite of HF rehospitalization or cardiovascular death (hazard ratio per log2 3.50; 95% CI 1.28-9.57; p =.014), independently of major AHF prognosticators, including B-type natriuretic peptide and renal function. However, no independent associations were found for all-cause rehospitalization or mortality. Despite a moderate correlation of IL-6 with C-reactive protein (CRP) levels (R = .51), the latter were not associated with clinical outcomes in this population. CONCLUSIONS: IL-6 levels associate with higher rate of cardiovascular events in AHF, independently of classical prognosticators and evidence of infection, outperforming CRP as an inflammatory outcome biomarker.

Anti-Remodeling Effects of Xanthohumol-Fortified Beer in Pulmonary Arterial Hypertension Mediated by ERK and AKT Inhibition.

Polyphenols present in some alcoholic beverages have been linked to beneficial effects in preventing cardiovascular diseases. Polyphenols found in beer with anti-proliferative and anti-cancer properties are appealing in the context of the quasi-malignant phenotype of pulmonary arterial hypertension (PAH). Our purpose was to evaluate if the chronic ingestion of a xanthohumol-fortified beer (FB) would be able to modulate the pathophysiology of experimental PAH. Male Wistar rats with monocrotaline (MCT)-induced PAH (60 mg/kg) were allowed to drink either xanthohumol-fortified beer (MCT + FB) or 5.2% ethanol (MCT + SHAM) for a period 4 weeks. At the end of the protocol, cardiopulmonary exercise testing and hemodynamic recordings were performed, followed by sample collection for further analysis. FB intake resulted in a significant attenuation of the pulmonary vascular remodeling in MCT + FB animals. This improvement was paralleled with the downregulation in expression of proteins responsible for proliferation (ERK1/2), cell viability (AKT), and apoptosis (BCL-XL). Moreover, MCT + FB animals presented improved right ventricle (RV) function and remodeling accompanied by VEGFR-2 pathway downregulation. The present study demonstrates that a regular consumption of xanthohumol through FB modulates major remodeling pathways activated in experimental PAH.

[Plasma concentration of lidocaine during bronchoscopy]. / Concentração plasmática de lidocaína durante a broncofibroscopia.

Lidocaine is commonly used for local anesthesia during fiberoptic bronchoscopy (FOB). It has been suggested that the total dose of lidocaine should be limited to 300-400 mg (or < 8.2 mg/kg). Lidocaine toxicity is directly correlated with its concentration in the blood and a threshold above which the side effects become more likely has been put at a plasma level of 5 microg/ml. The aim of our study was to determine plasmatic lidocaine concentrations (PLC), how often the PLC fall into the potentially toxic range and its correlation with adverse reactions. PLC were recorded in 30 patients undergoing FOB. Lidocaine was administered as a 2% gel, 10% spray and 2% solution. Venous blood samples were taken before the beginning of local anesthesia and at 20, 30 and 40 min thereafter. The mean total amount of lidocaine administered was 746.3 +/- 159.5 mg (11.6 +/- 3.1 mg/kg). Before the beginning of anesthesia, no significant levels of lidocaine were measurable in the patients. PLC were 3.2 +/- 1.7 (g/ml at 20 min., 3.3 +/- 1.7 microg/ml at 30 min. and 3.0 +/- 1.5 microg/ml at 40 min. The PLC exceeded toxic levels in 6 patients, but no complications were observed. Our data show that although the amount of lidocaine used in this study exceeded the recommended highest dose, no subjects had signs of toxicity. A maximum dose of lidocaine for topical anesthesia should be determined despite the fact that an average total dose superior to 400 mg appears to be safe in patients undergoing FOB.