Whole blood endotoxin responsiveness in patients with chronic heart failure: the importance of serum lipoproteins.
Background Endotoxin [lipopolysaccharide (LPS)] may be an important stimulus for cytokine release in patients with chronic heart failure (CHF). We sought to investigate the relationship between whole blood endotoxin responsiveness and serum lipoprotein concentrations. It is not known if low-dose LPS is sufficient to stimulate immune activation. Methods and results Whole blood from 32 CHF patients (mean age 66±2 years, NYHA class 2.7±0.2, five female) and 11 healthy control subjects (mean age 47±4 years, six female) was stimulated with LPS at nine different concentrations (0.001 to 10 ng/mL), and tumor necrosis factor (TNF-α) release was quantified. Reference standard endotoxin at concentrat…
Inflammation in right ventricular dysfunction due to thromboembolic pulmonary hypertension
Activation of the immune system is well established in patients with chronic heart failure (CHF) and impaired left ventricular function. High levels of pro-inflammatory cytokines are associated with a poor prognosis. Chronic thromboembolic pulmonary hypertension (CTEPH) frequently leads to impaired right ventricular function. It is not known whether such patients display chronic immune activation as well.We studied 49 patients with CTEPH (50±2 years, right ventricular ejection fraction [RVEF] 29±2%, left ventricular ejection fraction [LVEF] 51±3%, mean±SEM) and compared their results with 17 patients with CHF (71±2 years, LVEF 23±1%) and 34 age-matched control subjects (age 57±2 years). We …
Elevated levels of asymmetric dimethylarginine in chronic heart failure: a pathophysiologic link between oxygen radical load and impaired vasodilator capacity and the therapeuthic effect of allopurinol.
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide-dependent vasodilation. In 113 patients with chronic heart failure (CHF) and 26 controls, ADMA level was studied in relation to peripheral blood flow and vasodilator capacity. Further, the effects of allopurinol on concentrations of reactive oxygen species (ROS) and ADMA and peripheral vasodilator capacity were tested in a double-blind design. ADMA level was found to be elevated in CHF patients as compared with controls and increased in parallel with New York Heart Association (NYHA) class and exercise capacity (all P < 0.0001). The level of ADMA predicted resting blood flow (P < 0.05) and postischemic vasodilator…
Importance of selenium status in patients with chronic heart failure
Abstract Overactivity of the immune system may be a worthwhile therapeutic target for implementing prognostic improvements. Therefore the impact of lipopolysaccharide (LPS) desensitization on survival may help in the development of novel therapies. An understanding of the pathophysiology of the trace element selenium may complement such approaches, as recent data suggest that inflammatory responses are selenium-dependent.
Exercise intensity assessment and prescription in cardiovascular rehabilitation and beyond : why and how : a position statement from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology
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Leukocyte Redistribution: Effects of Beta Blockers in Patients with Chronic Heart Failure
BACKGROUND:Overproduction of pro-inflammatory cytokines is a well established factor in the progression of chronic heart failure (CHF). Changes in cellular immunity have not been widely studied, and the impact of standard medication is uncertain. Here we investigate whether a leukocyte redistribution occurs in CHF and whether this effect is influenced by beta-blocker therapy. METHODOLOGY:We prospectively studied 75 patients with systolic CHF (age: 68+/-11 years, left ventricular ejection fraction 32+/-11%, New York Heart Association class 2.5+/-0.7) and 20 age-matched healthy control subjects (age: 63+/-10 years). We measured the response of cells to endotoxin exposure in vitro, analysed su…
Heat shock protein 70 in patients with chronic heart failure: relation to disease severity and survival
Heat shock protein 70 (Hsp70) is essential for cellular recovery, survival and maintenance of cellular function. Research into the possible use of Hsp70 as a cytoprotective therapeutic agent is ongoing. Chronic heart failure (CHF) is a state associated with systemic inflammation, particularly in patients with cardiac cachexia. We hypothesised that circulating Hsp70 levels are elevated in patients with CHF, more so in cachechtic patients, and that Hsp70 levels would relate to mortality.We studied 107 patients (28 female, age 67+/-1 years, NYHA class 2.6+/-0.6 and LVEF 29+/-1%, mean+/-SEM) and 21 controls. Cardiac cachexia was present in 32 patients. Hsp70 was detectable in 41% of CHF patient…
The relationship between age and production of tumour necrosis factor-α in healthy volunteers and patients with chronic heart failure
Ageing is associated with an altered immune response. Elevated plasma levels of tumour necrosis factor-alpha (TNF-alpha) are present in patients with advanced chronic heart failure (CHF). However, the relationship between age and the immune response in CHF is unknown.We investigated the relationship between age and the TNF-alpha generating capacity of lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) in nine healthy control subjects (mean age 51.6+/-3.6 years, age range 39-75 years) and 22 stable patients with CHF (mean age 68.3+/-1.5 years, age range 52-78 years, NYHA class 3.0+/-0.2). We also tested the TNF-alpha generating capacity of all control subjects and …