Early Expression of Pro- and Anti-Inflammatory Cytokines in Left Ventricular Assist Device Recipients With Multiple Organ Failure Syndrome

To assess whether the combined evaluation of total Sequential Organ Failure Assessment (t-SOFA) score and pro- and anti-inflammatory cytokine profiles early after left ventricular assist device (LVAD) implant discriminates patients at high risk for multiple organ failure syndrome (MOFS) in the first month post-LVA

Acute cigarette smoking impairs microvascular function in young moderate smokers: A potential model for studying vasoactive properties of food bioactives

It has been suggested that several dietary compounds may improve endothelial dysfunction and oxidative stress induced by smoking. We investigated the effects of acute smoking on blood pressure, heart rate (HR), peripheral arterial function (reactive hyperemia index, RHI), and arterial stiffness in young smokers by Endo-PAT2000. Twenty subjects that smoked an average of 15 cigarettes per day participated in the study. Reactive Hyperemia Index, arterial stiffness, blood pressure and HR were assessed before and after smoking one cigarette. Acute smoking significantly reduced RHI by 28% while increased arterial systolic ( + 14%) and diastolic ( + 10%) blood pressure and HR ( + 13%) at 5 min, while no effect was observed after 30 min. Arterial stiffness was not significantly affected. A significant, positive correlation was found between total serum cholesterol concentration and post-smoking arterial stiffness values. This study demonstrates that acute cigarette smoking impairs RHI and vital signs in young moderate smokers as evaluated through a non-invasive technique. Additionally, the experimental model described, where a decrease of RHI is induced by cigarette smoking, may be useful to study the impact of dietary vasoactive compounds on endothelial function

A single serving of blueberry (V. corymbosum) modulates peripheral arterial dysfunction induced by acute cigarette smoking in young volunteers: a randomized-controlled trial

Cigarette smoking causes oxidative stress, hypertension and endothelial dysfunction. Polyphenol-rich foods may prevent these conditions. We investigated the effect of a single serving of fresh-frozen blueberry intake on peripheral arterial function and arterial stiffness in young smokers. Sixteen male smokers were recruited for a 3-armed randomized-controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300 g of blueberry) + smoking; control treatment (300 mL of water with sugar) + smoking. Each treatment was separated by one week of wash-out period. The blood pressure, heart rate, peripheral arterial function (reactive hyperemia and Framingham reactive hyperemia), and arterial stiffness (digital augmentation index, digital augmentation index normalized for a heart rate of 75 bpm) were measured before and 20 min after smoking with Endo-PAT2000. Smoking impaired the blood pressure, heart rate and peripheral arterial function, but did not affect the arterial stiffness. Blueberry consumption counteracted the impairment of the reactive hyperemia index induced by smoking (?\u274.4 ? 0.8% blueberry treatment vs. ?\u2722.0 ? 1.1% smoking treatment, p < 0.01) and Framingham reactive hyperemia (+28.3 ? 19.2% blueberry treatment vs. ?\u2742.8 ? 20.0% smoking treatment, p < 0.0001), and the increase of systolic blood pressure (+8.4 ? 0.02% blueberry treatment vs. +13.1 ? 0.02% smoking treatment, mmHg, p < 0.05) after cigarette smoking. No effect was observed for arterial stiffness and other vital signs. In conclusion, data obtained suggest a protective role of blueberry on reactive hyperemia, Framingham reactive hyperemia, and systolic blood pressure in subjects exposed to smoke of one cigarette. Future studies are necessary to elucidate the mechanisms involved

Effects of Sapropterin on Endothelium-Dependent Vasodilation in Patients With CADASIL: A Randomized Controlled Trial

Background and Purpose-Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a rare autosomal dominant disorder caused by NOTCH3 mutations, is characterized by vascular smooth muscle and endothelial cells abnormalities, altered vasoreactivity, and recurrent lacunar infarcts. Vasomotor function may represent a key factor for disease progression. Tetrahydrobiopterin, essential cofactor for nitric oxide synthesis in endothelial cells, ameliorates endothelial function. We assessed whether supplementation with sapropterin, a synthetic tetrahydrobiopterin analog, improves endothelium-dependent vasodilation in CADASIL patients

Paraoxonase 1 L55M, Q192R and paraoxonase 2 S311C alleles in atherothrombosis

Increased oxidative stress is known to play a role in the pathogenesis of atherosclerosis, and polymorphisms in genes encoding for enzymes involved in modulation of oxidant stress, such as paraoxonases (PONs), provide a potentially powerful approach to study the risk of disease susceptibility. Aim of our study is to investigate the possible association among PONs polymorphisms, clinical and metabolic factors, and atherothrombotic events in an Italian population. We evaluated in 105 subjects, with or without atherosclerotic risk factors, the presence of PON1 L55M, PON1 Q192R, and PON2 S311C genetic variants, as well as lipid profile, the concentration of aminothiols (blood reduced glutathione, plasma total glutathione, homocysteine, cysteine, cysteinyl glycine), and malondialdehyde as markers of lipid peroxidation

Time-course of plasma NT-proc-type natriuretic peptide in end-stage heart failure patients supported by left ventricular assist device implant

Purpose: Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) as well as the respective amino-terminal NT-proANP and NT-proBNP have now been well established as predictors of outcome in patients with heart failure (HF). C-type natriuretic peptide (CNP) and NT-proCNP are increased in HF patients as a function of disease severity, supporting a role for these peptides in the pathophysiology of HF, but their modifications during left ventricular assist device (LVAD) implant are lacking. Aim of this study was to evaluate the time-course of natriuretic peptides in end-stage HF patients undergoing LVAD implant in order to recognize new reliable predictive biomakers of cardiac recovery during LVAD. Methods: Five end-stage HF patients (NYHA class III and IV; age: 57?11 yrs; LVEF%<20) undergoing LVAD implantation were studied. Clinical hemodynamic evaluation and blood samples were obtained at admission (T1) and at 4, 24, 72 hrs and 1, 2, 4 weeks (T2-T7) after LVAD implant. NT-proANP and NT-proCNP were measured in plasma EDTA and aprotinin samples by a direct ELISA () while NT-proBNP by the Elecsys? 2010 analyzer. Results: The NT-proCNP time-course during LVAD was the following: T1=88.8?12.8 pg/ml; T2=144?29.8; T3=241.6?86.8 (p<0.05 vs T1); T4=229.7?66.4; T5=162.3?66.5; T6=175.3?47.7; T7=76.9?8 (p=ns vs T1). NT-proANP showed a similar pathway while NT-proBNP is reduced after LVAD implant (T1=4.1?2.2 ng/ml; T3=3.0?0.4), remaining lower than at baseline until 4 weeks (T7=3.1?0.9 ng/ml). NT-proCNP positively correlated with NT-proANP (p=0.03) while no correlation was found with NT-proBNP. Conclusions: This study reports for the first time original data on NT-proCNP levels after LVAD as a function of the time. The natriuretic peptides are differently modulated by LVAD, although all peptides resulted reduced after 4 weeks from implantation. The parallel determination of these effectors could allow us to obtain an integrated description of pathophysiological changes occurring during mechanical support

Is the Oxidant/Antioxidant Status Altered in CADASIL Patients?

The altered aggregation of proteins in non-native conformation is associated with endoplasmic reticulum derangements, mitochondrial dysfunction and excessive production of reactive oxygen species. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary systemic vasculopathy, caused by NOTCH3 mutations within the receptor extracellular domain, that lead to abnormal accumulation of the mutated protein in the vascular wall. NOTCH3 misfolding could cause free radicals increase also in CADASIL. Aim of the study was to verify whether CADASIL patients have increased oxidative stress compared to unrelated healthy controls. We enrolled 15 CADASIL patients and 16 gender- and age-matched healthy controls with comparable cardiovascular risk factor. Blood and plasma reduced and total aminothiols (homocysteine, cysteine, glutathione, cysteinylglycine) were measured by HPLC and plasma 3- nitrotyrosine by ELISA. Only plasma reduced cysteine (Pr-Cys) and blood reduced glutathione (Br-GSH) concentrations differed between groups: in CADASIL patients Br-GSH levels were higher (p = 0.019) and Pr-Cys lower (p = 0.010) than in controls. No correlation was found between Br-GSH and Pr-Cys either in CADASIL patients (rho 0.25, P=0.36) or in controls (rho -0.15, P=0.44). Conversely, 3- nitrotyrosine values were similar in CADASIL and healthy subjects (p = 0.82). The high levels of antioxidant molecules and low levels of oxidant mediators found in our CADASIL population might either be expression of an effective protective action against free radical formation at an early stage of clinical symptoms or they could suggest that oxidative stress is not directly involved in the pathogenesis of CADASIL

Neopterin levels are independently associated with cardiac remodeling in patients with chronic heart failure

Neopterin, a marker of inflammation and monocyte activation, is found increased in patients with heart failure (HF). This study investigates whether neopterin levels correlate with left ventricular (LV) remodeling and brain natriuretic peptide (BNP), a marker of cardiac stress, in chronic HF (CHF) patients with different severity of disease. The relationship between elevated neopterin levels and LV enlargement in CHF patients suggests a crucial role of monocyte activation in the development of cardiac dysfunction in CHF patients. Assessment of neopterin levels is a potential biomarker to evaluate the progression of LV remodeling in CHF patients

Relationship between Early Inflammatory Response and Clinical Evolution of the Severe Multiorgan Failure in Mechanical Circulatory Support-Treated Patients

Background. The mechanical circulatory support (MCS) is an effective treatment in critically ill patients with end-stage heart failure (ESHF) that, however, may cause a severe multiorgan failure syndrome (MOFS) in these subjects. The impact of altered inflammatory response, associated to MOFS, on clinical evolution of MCS postimplantation patients has not been yet clarified. Methods. Circulating cytokines, adhesion molecules, and a marker of monocyte activation (neopterin) were determined in 53MCStreated patients, at preimplant and until 2 weeks. MOFS was evaluated by total sequential organ failure assessment score (tSOFA). Results. During MCS treatment, 32 patients experienced moderate MOFS (tSOFA< 11; A group), while 21 patients experienced severe MOFS (tSOFA? 11) with favorable (B group) or adverse (&#55349;&#56411; = 13, C group) outcomes. At preimplant, higher values of left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) were the only parameter independently associated with A group. In C group, during the first postoperative week, high levels of interleukin-8 (IL-8) and tumor necrosis factor (TNF)-&#55349;&#57084;, and an increase of neopterin and adhesionmolecules, precede tSOFA worsening and exitus. Conclusions.TheMCS patients of C group show an excessive release to IL-8 and TNF-&#55349;&#57084;, and monocyte-endothelial activation after surgery, that might contribute to the unfavourable evolution of severe MOFS

Plasma Total Cysteine and Cardiovascular Risk Burden: Action and Interaction

We hypothesized that redox analysis could provide sensitive markers of the oxidative pathway associated to the presence of an increasing number of cardiovascular risk factors (RFs), independently of type. We classified 304 subjects without cardiovascular disease into 4 groups according to the total number of RFs (smoking, hypertension, hypercholesterolaemia, hyperhomocysteinaemia, diabetes, obesity, and their combination). Oxidative stress was evaluated by measuring plasma total and reduced homocysteine, cysteine (Cys), glutathione, cysteinylglycine, blood reduced glutathione, and malondialdehyde. Twenty-seven percent of subjects were in group 0 RF, 26% in 1 RF, 31% in 2 RF, and 16% in ≥3 RF. By multivariable ordinal regression analysis, plasma total Cys was associated to a higher number of RF (OR = 1.068; 95% CI = 1.027–1.110, P = 0.002). Total RF burden is associated with increased total Cys levels. These findings support a prooxidant effect of Cys in conjunction with RF burden, and shed light on the pathophysiologic role of redox state unbalance in preclinical atherosclerosis