Torbjørn Aarsland

Effect of aerobic exercise training on plasma levels of tumor necrosis factor alpha in patients with heart failure.

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Effect of exercise training on skeletal muscle fibre characteristics in men with chronic heart failure. Correlation between skeletal muscle alterations, cytokines and exercise capacity.

BACKGROUND In patients with congestive heart failure (CHF) there is a shift from aerobic type I muscle fibres to less aerobic type II fibres. Exercise training has been shown to have beneficial effects on exercise performance, peripheral pathology and the neurohumoral profile in stable patients with CHF. This study evaluated the effect of a 3 month exercise training program on skeletal muscle characteristics and the correlation of these to cytokines and exercise capacity in CHF patients. METHODS Skeletal muscle biopsies for enzyme-histochemical analysis were performed in 15 CHF patients in New York Heart Association classes II-III, with a mean ejection fraction of 33+/-5% before and after a 12 week training period. The patients were trained for 30 min, five times a week at 80% of the peak heart rate achieved at baseline ergometer cycle test. Fifteen healthy men were used as controls. Plasma samples were examined by enzyme immunoassays for levels of pro-inflammatory cytokines. RESULTS (a) At baseline we found muscle atrophy in five of the patients. The percent area of type I fibres (40.7+/-12.0 vs. 56.4+/-11.0%, P<0.05) and the thickness of type IIA (56.10+/-7.8 vs. 71.6+/-11.9 microm, P<0.001) and B-fibres (49.0+/-8.9 vs. 63.9+/-10.6 microm, P<0.001) were reduced, whereas the percent area of type IIA fibres (52.1+/-13.3 vs. 36.4+/-9.9%, P<0.05) was increased in heart failure patients compared to healthy controls. There was a modest correlation between fibre thickness and the level of interleukin 6 (r=-0.657, P=0.008). (b) After exercise training there was a reduction in muscle area examined by light-microscopy, measured as a percentage of field (-2.7, P=0.003) with an concomitant increase in interstitium. This reduction correlated to the increase in the 6-min walk test (r=-0.558, P=0.031). The thickness of type IIB fibres increased (+5.6 microm, P=0.068) and the area of type I fibres decreased (-6.1%, P=0.062). CONCLUSIONS Patients with CHF have a relatively increased area of type IIA fibres and a relatively decreased area of type I fibres compared to healthy individuals. The thickness of type IIA and type IIB fibres is decreased compared to normal individuals. A modest negative correlation between the level of interleukin 6 and fibre thickness at baseline, suggests that inflammatory cytokines may be involved in the pathogenesis of the CHF related myopathy. A significant correlation between the reduction of muscle area, with increased interstitum, and the increase in the 6-min walk test may indicate that the improvement is due to increased capillary density permitting better flow reserve to exercising muscles.

The effects of chronic, sustained-release moxonidine therapy on clinical and neurohumoral status in patients with heart failure

AIMS Congestive heart failure (CHF) is characterized by elevated plasma norepinephrine (PNE) associated with a poor prognosis. Moxonidine selectively stimulates medullary imidazoline receptors which centrally inhibit sympathetic outflow and potently suppress levels of circulating PNE. This study was designed to evaluate the effects of central sympathetic inhibition on clinical and neurohumoral status in patients with CHF. METHODS AND RESULTS This study evaluated 25 patients (age=69+/-7 years, 20 males) with symptomatic CHF (NYHA II-III), stabilized on standard therapy. The mean ejection fraction was 28+/-7% at baseline. Patients were titrated in a double-blind fashion to 11 weeks of oral therapy with placebo (n=9) or sustained-release (SR) moxonidine 0.9 mg bid (n=16). Clinical and neurohumoral status were evaluated at baseline, on chronic therapy at the target dose, and during cessation of therapy. All patients completed the trial and reached the target dose. Dry mouth, symptomatic hypotension, and asthenia were more frequent in the moxonidine SR-treated group. PNE was substantially reduced after 6 weeks at the maximum dose (0.9 mg bid) by 50% vs. placebo (P<0. 0005). A reduction in 24-h mean heart rate (P<0.01) was correlated to the reduction in PNE (r=0.70, P<0.05). A 36% increase in the standard deviation of normal-to-normal intervals (SDNN) was observed in the moxonidine SR group vs. a 2% decrease for placebo (P=0.06); for the root mean square of successive differences (rMSSD), there was a 21% increase for moxonidine SR vs. a 19% decrease for placebo (P<0.05). Abrupt cessation of chronic therapy resulted in substantial increases in PNE, blood pressure, and heart rate. CONCLUSIONS Chronic therapy with a sustained-release formulation of moxonidine in patients with CHF was well tolerated, with substantial and sustained reductions in PNE. The tachyarrhythmias were attenuated, with evidence of improved autonomic tone. Due to the observed effects following moxonidine discontinuation, tapering of therapy is recommended.

Acute hemodynamic and neurohumoral effects of moxonidine in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Elevated plasma norepinephrine (PNE) has been shown to be an important predictor of morbidity and mortality in patients with congestive heart failure (CHF). Moxonidine selectively stimulates imidazoline receptors located in the medulla, which centrally inhibit sympathetic outflow. PNE is suppressed and peripheral vasodilation reduces systemic blood pressure. This study evaluated the acute neurohumoral and hemodynamic effects of a single dose of oral moxonidine in 32 patients (22 men, mean +/- SD age 66 +/- 10 years) with CHF. All patients were in New York Heart Association functional class III and stabilized on chronic therapy with diuretics, digitalis, and angiotensin-converting enzyme inhibitors. The mean PNE concentration was 509 +/- 304 pg/ml at baseline. Patients underwent invasive hemodynamic monitoring after double-blind randomization to either placebo (n = 12), moxonidine 0.4 mg (n = 9), or moxonidine 0.6 mg (n = 11). Moxonidine produced a dose-dependent, vasodilator response compared with placebo. Analysis of the time-averaged change from baseline over 6 hours demonstrated that moxonidine 0.6 mg caused significant reductions in mean systemic arterial pressure (p <0.0001), mean pulmonary arterial pressure (p <0.005), systemic vascular resistance (p <0.05), pulmonary vascular resistance (p <0.01), and heart rate (p <0.05). Stroke volume was unchanged. PNE was reduced substantially (-180 pg/ml at 4 hours, p <0.005) and the reduction was highly correlated with the baseline level (r = -0.968). Moxonidine was well tolerated in this single-dose study and resulted in a modest, dose-dependent, vasodilator response, with substantial reductions in systemic and pulmonary arterial blood pressure. Trials designed to evaluate the clinical efficacy of chronic moxonidine therapy in CHF added to conventional therapy would be appropriate.

Omega-3 index and prognosis in acute coronary chest pain patients with a low dietary intake of omega-3

Abstract Background. The omega-3 index (eicosapentaenoic acid + docosahexaenoic acid) content in red blood cell membranes has been suggested as a novel risk marker for cardiac death. Objective. To assess the ability of the omega-3 index to predict all-cause mortality, cardiac death and sudden cardiac death following hospitalization with an acute coronary syndrome (ACS), and to include arachidonic acid (AA) in risk assessment. Material and methods. The omega-3 index was measured in 572 consecutive patients (median 63 years and 59% males) admitted with chest pain and suspected ACS in an inland Northern Argentinean city with a dietary habit that was essentially based on red meat and a low intake of fish. Clinical endpoints were collected during a 5-year follow-up period, median 3.6 years, range 1 day to 5.5 years. Stepwise Cox regression analysis was employed to compare the rate of new events in the quartiles of the omega-3 index measured at inclusion. Multivariable analysis was performed. Results. No statistical significant differences in baseline characteristics were noted between quartiles of the omega-3 index. The median of the adjusted omega-3 index was 3.6%. During the follow-up period, 100 (17.5%) patients died. Event rates were similar in all quartiles of the omega-3 index, with no statistical significant differences. AA added no prognostic information. Conclusion. In a population with a low intake of fish and fish oils, the adjusted omega-3 index did not predict fatal events following hospitalization in patients with acute chest pain and suspected ACS.

The Argentinian mother-and-child contaminant study: a cross-sectional study among delivering women in the cities of Ushuaia and Salta

ABSTRACT Several ongoing international multidisciplinary projects have examined linkages between environmental chemicals and health. In contrast to Arctic regions, information for the Southern Hemisphere is scarce. Because of the inherent practice of pesticide utilisation and mismanagement, food security is potentially threatened. The most vulnerable period in human life occurs during pregnancy and early childhood, thus a focus on the body burdens of PTS in pregnant or delivering women is warranted. The current study was designed to investigate health risks related to exposure to PTS and food security in two regions of Argentina (Ushuaia and Salta). Our aims were to quantify concentrations of organic and inorganic toxins in serum or whole blood of delivering women and to collect pertinent dietary and medical information. The overall study design, the basic demographic features and essential clinical chemistry findings are described in the current paper. The socioeconomic differences between the two study areas were evident. On average, the women in Ushuaia were 4 years older than those in Salta (28.8 vs. 24.7 years). Respectively, the proportion of current smokers was 4.5 vs. 9.6%; and Salta had a higher birth rate, with 15.6% being para four or more. Saltanean women reported longer breastfeeding periods. Caesarean sections were more frequent in Ushuaia, with 43% of Caesarean deliveries compared with only 6% in Salta. Employment was high in both communities. Recognised environmental pollution sources in the vicinity of participant dwellings were widespread in Salta (56.1%) compared to Ushuaia (9%). The use of pesticides for insect control in homes was most common in Salta (80%). There is an urgent need for a comprehensive assessment of exposures in areas of the Southern Hemisphere. Our data set and the planned publications of observed concentrations of inorganic and organic environmental contaminants in both mothers and their newborns will contribute to this objective.