Aminothiol redox alterations in patients with chronic heart failure of ischaemic or non-ischaemic origin.

OBJECTIVE: Oxidative stress plays a role in the progression of chronic heart failure (CHF), but whether and how ischaemic heart disease (IHD) or non-IHD aetiology may account for differential redox alterations is currently unclear. We assessed the relation between thiol redox state and lipid peroxidation, as a marker of oxidative stress, in patients with CHF of ischaemic or non-ischaemic origin. METHODS: Blood reduced glutathione, plasma total and reduced cysteine, cysteinylglycine, homocysteine, glutathione, plasma alpha-tocopherol, ascorbic acid, and free malondialdehyde were assessed in 43 CHF heart transplant candidates (24 IHD and 19 non-IHD) and 30 controls matched for age, gender and number of atherosclerotic risk factors. RESULTS: Reduced cysteine was increased in CHF patients compared with controls. The highest levels were found in IHD versus non-IHD patients versus controls. Malondialdehyde levels were significantly higher in IHD patients than in controls, whereas antioxidant vitamins did not differ among the three groups. CONCLUSIONS: Specific abnormalities in the thiol pattern are associated with heart failure aetiology in CHF patients. Our findings point to the possible role of reduced cysteine in the progression of chronic IHD to heart failure status, as an additional pro-oxidant stimulus for worsening oxidative stress.

Redox state, oxidative stress and endothelial dysfunction in heart failure: the puzzle of nitrate-thiol interaction.

Endothelial dysfunction, a critical component in the progression of heart failure, may result from increased oxidative stress, secondary to activation of the adrenergic and the renin-angiotensin systems and to the production of inflammatory cytokines, which in turn contribute to reduced bioavailability of nitric oxide (NO). Oxidative stress, determined by excess production of reactive oxygen species and impairment in the antioxidant defence, is responsible for both the decline of diffusible NO and the decrease in the concentration of essential co-factors of NO synthases. Reactive oxygen species are formed from NO in the presence of oxidants and are involved in the nitration of protein tyrosine residue that can alter protein function. Recent studies re-addressed the impact of nitrate treatment in heart failure in view of the beneficial vascular and cellular effects of NO, and of the discovery of abnormalities in NO pathways in this disease. Concerns exist, however, on the safety of nitrates in this setting. Nitrates stimulate vascular superoxide anion production via activation of NADPH oxidase, and induction of uncoupling of NO synthase. Furthermore, by using donors of sulfhydryl groups, such as cysteine and glutathione, for NO production, nitrates may favour depletion of the intracellular thiol pool, thus impairing the antioxidant defence mechanisms.

Blood glutathione as independent marker of lipid peroxidation in heart failure.

BACKGROUND: Aminothiols have a critical function as intracellular redox buffers and constitute furthermore an important extracellular redox system. Lipid peroxidation is increased in chronic heart failure (CHF), but the contribution of each thiol to oxidative stress in this syndrome has not been evaluated. AIM: To assess the correlation between blood and plasma concentrations of aminothiols and lipid peroxidation as marker of oxidative stress in CHF patients. METHODS: Blood reduced glutathione (GSH), plasma total and reduced cysteine, cysteinylglycine, homocysteine, GSH, alpha-tocopherol, ascorbic acid, and free malondialdehyde (MDA) were assessed in samples obtained from 26 CHF heart transplant candidates and 26 age- and gender-matched controls with atherosclerotic risk factors and no history of cardiovascular disease. Results are expressed as median and interquartile range (I-III). RESULTS: MDA levels were significantly higher in CHF patients than in controls [1.03 (0.56-1.60) microM vs. 0.70 (0.40-0.83) microM, p=0.006]. Blood reduced GSH concentrations were significantly higher [662 (327-867) microM vs. 416 (248-571) microM, p=0.016], while alpha-tocopherol levels were significantly lower [15 (13-19) microM vs. 21 (17-32) microM, p=0.001] in CHF patients than in controls. By multivariate logistic regression analysis, the only independent predictors of lipid peroxidation, as expressed by MDA levels > or = 1.00 microM, were increased blood GSH concentrations (OR 1.003 per unit, 95% CI 1.001 to 1.006, p=0.008), ischemic (OR 20, 95% CI 2.6 to 155, p=0.004) and non ischemic CHF etiology (OR 11, 95% CI 1.3 to 99, p=0.026). CONCLUSIONS: Abnormalities in intracellular GSH cycling are associated to increased lipid peroxidation in CHF.

[Use of imaging in the evaluation of heart transplant recipients]. / Tecniche di imaging a confronto nella valutazione del paziente cardiotrapiantato.

Common complications after heart transplantation include acute rejection and coronary allograft vasculopathy. In order to detect the presence of rejection, tissue Doppler imaging echocardiography provides high accuracy and allows to optimize the timing of endomyocardial biopsies, which remain the cornerstone in rejection diagnosis. Coronary allograft vasculopathy is often a diffuse disease so that it is difficult to recognize by imaging modalities, such as myocardial perfusion scintigraphy, which are based on intra-patient comparison of different areas. Quantitative assessment of the myocardial blood flow by positron emission tomography overcomes this issue. Dobutamine stress echocardiography provides accurate diagnosis as well as useful prognostic information. Nevertheless, intracoronary ultrasound is nowadays considered the gold standard for vasculopathy assessment, since it is able to detect a minimum intimal thickening which represents the early feature of disease. Magnetic resonance represents the most attractive approach, though it has not yet gained widespread clinical use.

Drugs for left ventricular remodeling in heart failure.

Left ventricular (LV) remodeling (ie, enlargement and functional deterioration occurring over time) is among the main mechanisms of progression in heart failure (HF). LV dilatation and dysfunction are major negative prognostic markers in patients with HF. Treatments that are effective in limiting or even reversing this process can be expected to provide clinical benefit. Changes in LV dimensions rather than in ejection fraction should be used to monitor remodeling. Ejection fraction can be influenced by transient loading conditions and by agents that stimulate contractility at the expense of increased oxygen demand, whereas dimensional changes probably reflect structural modifications occurring in the myocardium. The neurohormonal antagonists that have been demonstrated to reduce mortality and morbidity in HF (angiotensin-converting enzyme inhibitors [ACE], beta-blockers, angiotensin receptor blockers, and aldosterone antagonists) are also able to inhibit or reverse remodeling. In reverse remodeling, beta-blockers appear to be superior to the other classes of drugs, with a stronger correlation between dose and effect, but it must be remembered that they have been tested as an addition to background therapy that may include ACE inhibitors. With regard to nonpharmacologic strategies, biventricular pacing is associated with functional improvement and reverse remodeling in patients with advanced HF and electromechanical dyssynchrony, and it recently has been demonstrated to improve survival in a randomized clinical trial.