Biomedical subjects

Stamatis Adamopoulos

Publications and source records attributed to Stamatis Adamopoulos.

30 records · Page 2Linked to original sources

PubMed2003

Effects of growth hormone on circulating cytokine network, and left ventricular contractile performance and geometry in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Recent experimental and clinical data indicate that abnormal central and peripheral immune reactions contribute to the progression of chronic heart failure, and that immunomodulation may be an important therapeutic approach in this syndrome. Aims We sought to study the effects of growth hormone (GH) administration on circulating pro-inflammatory/anti-inflammatory cytokine balance, and to investigate whether these GH-induced immunomodulatory effects are associated with the improvement of left ventricular (LV) contractile performance in idiopathic dilated cardiomyopathy (DCM) patients. METHODS: Plasma pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and its soluble receptor (sGM-CSFR), chemotactic cytokine macrophage chemoattractant protein-1 (MCP-1), soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1), and, finally, anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-beta2 (TGF-beta2) were measured (ELISA method) in 12 patients with DCM (NYHA class III; LV ejection fraction: 23.6+/-1.7%) before and after a 3-month subcutaneous administration of GH 4IU every other day (randomized crossover design). Peak oxygen uptake (VO2 max), LV dimensions, LV mass index, end-systolic wall stress (ESWS), mean velocity of circumferential fibre shortening (Vcfc), and contractile reserve (change of ratio Vcfc/ESWS after dobutamine administration) were also determined at the same period. RESULTS: Treatment with GH produced a significant reduction in plasma TNF-alpha (7.8+/-1.1 vs 5.5+/-0.9pg/ml, P=0.013), IL-6 (5.7+/-0.5 vs 4.7+/-0.4pg/ml, P=0.043), GM-CSF (27.3+/-1.7 vs 23.3+/-1.8pg/ml, P=0.042), sGM-CSFR (4.0+/-0.4 vs 3.2+/-0.4ng/ml, P=0.039), MCP-1 (199+/-5 vs 184+/-6pg/ml, P=0.048), sICAM-1 (324+/-34 vs 274+/-27ng/ml, P=0.008) and sVCAM-1 (1238+/-89 vs 1043+/-77ng/ml, P=0.002) in DCM patients. A significant increase in ratios IL-10/TNF-alpha (1.9+/-0.3 vs 3.5+/-0.9, P=0.049), IL-10/IL-6(2.6+/-0.6 vs 3.2+/-0.5, P=0.044) and TGF-beta2/TNF-alpha (3.1+/-0.6 vs 4.4+/-0.6, P=0.05) was alsofound with GH therapy. A significant reduction in ESWS (841+/-62 vs 634+/-48gr/cm(2), P=0.0026) and LV end-systolic volume index (LVESVI, 128+/-12 vs 102+/-12ml, P=0.035) as well as a significant increase in posterior wall thickness (PWTH, 9.2+/-0.5 vs 10.3+/-0.6mm, P=0.034), contractile reserve (0.00029+/-0.0001 vs 0.00054+/-0.0001circ*cm(2)/gr*s, P=0.00028) and VO2max (15.3+/-0.7 vs 17.1+/-0.9ml/kg/min, P=0.002) were observed after GH administration. Good correlations were found between GH-induced increase in contractile reserve and the increases in VO2max (r=0.63, P=0.028), IL-10/TNF-alpha (r=0.69, P=0.011) and TGF-beta2/TNF-alpha (r=0.58, P=0.046) ratios, as well as the reduction in plasma TNF-alpha levels (r=-0.86, P=0.0004). CONCLUSIONS: GH administration modulates beneficially circulating cytokine network and soluble adhesion molecules in patients with DCM, whilst enhancing contractile reserve and diminishing LV volumes. These GH-induced anti-inflammatory effects may be associated with the improvement in LV contractile performance and exercise capacity as well as with the reverse of LV remodelling of patients with DCM.

Analysis of Variance↗

PubMed2003

Effects of dobutamine on left ventricular shape and geometry: an easy way to detect the functional status of chronic heart failure in patients with dilated cardiomyopathy.

OBJECTIVE: Changes in left ventricular geometry and shape are prominent characteristics of cardiomyopathy. The aim of this study was to investigate left ventricular geometry and shape changes after inotropic stimulation in patients with chronic nonischemic dilated cardiomyopathy. METHODS: A low infusion rate echocardiography-dobutamine study was performed in 35 consecutive patients (age: 50 +/- 8 years) with known dilated cardiomyopathy. Peak exercise oxygen consumption was measured the day before. Overall left ventricular chamber shape was assessed by using the long-/minor-axis dimension ratio obtained at end-diastole and end-systole. RESULTS: After dobutamine infusion, in the entire study group an increase in systolic long-/minor-axis dimension ratio (0.11 +/- 0.13 mm, P <.001) was observed. The study population was further divided according to whether peak exercise oxygen consumption was less (group I) or more (group II) than 14 mL/kg/min. Although at baseline systolic long-/minor-axis dimension ratio was similar between groups, after dobutamine infusion it was higher in group II (1.51 +/- 0.19) than in group I (1.31 +/- 0.2, P <.01) indicating the abnormal response of systolic sphericity index to inotropic stimulation in patients with advanced functional class heart failure. CONCLUSION: The response of systolic sphericity index to dobutamine infusion might be an alternative index of the functional status of the failing heart in patients with nonischemic dilated cardiomyopathy.

Adult↗

PubMed2003

Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human.

In human disease and experimental animal models, depressed Ca(2+) handling in failing cardiomyocytes is widely attributed to impaired sarcoplasmic reticulum (SR) function. In mice, disruption of the PLN gene encoding phospholamban (PLN) or expression of dominant-negative PLN mutants enhances SR and cardiac function, but effects of PLN mutations in humans are unknown. Here, a T116G point mutation, substituting a termination codon for Leu-39 (L39stop), was identified in two families with hereditary heart failure. The heterozygous individuals exhibited hypertrophy without diminished contractile performance. Strikingly, both individuals homozygous for L39stop developed dilated cardiomyopathy and heart failure, requiring cardiac transplantation at ages 16 and 27. An over 50% reduction in PLN mRNA and no detectable PLN protein were noted in one explanted heart. The expression of recombinant PLN-L39stop in human embryonic kidney (HEK) 293 cells and adult rat cardiomyocytes showed no PLN inhibition of SR Ca(2+)-ATPase and the virtual absence of stable PLN expression; where PLN was expressed, it was misrouted to the cytosol or plasma membrane. These findings describe a naturally-occurring loss-of-function human PLN mutation (PLN null). In contrast to reported benefits of PLN ablation in mouse heart failure, humans lacking PLN develop lethal dilated cardiomyopathy.

Animals↗

PubMed2003

Chemokines in cardiovascular remodeling: clinical and therapeutic implications.

Chemokines are newly discovered molecules that mediate the migration of leukocytes into inflammed tissues and control the inflammatory reactions in various immune-mediated diseases. Both in animal models and in human specimens, chemokine expression is associated with atherosclerotic lesion development and vascular remodeling and restenosis after angioplasty. Furthermore, recent studies have demonstrated that chemokines play an important role in the pathophysiology of acute coronary syndromes, post-infarction left ventricular remodeling and chronic heart failure. The capacity to control activation and movement of inflammatory cells suggests that chemokines and their receptors might provide novel targets for therapeutic intervention in a number of conditions characterized by chronic inflammation, including cardiovascular diseases. The present review summarizes current knowledge regarding the potential pathogenic role of chemokines in major cardiovascular disorders, as well as the modulation of the chemokine network as a novel, interesting therapeutic modality in this field.

Animals↗

PubMed2002

Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic heart failure.

OBJECTIVES: We sought to investigate the effects of physical training on circulating proinflammatory cytokines and the soluble apoptosis mediators Fas (sFas) and Fas ligand (sFasL) in patients with chronic heart failure (CHF). BACKGROUND: Recent investigations have shown an overexpression of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with CHF, which may be related to their exercise intolerance and clinical deterioration. METHODS: Plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors I and II (sTNF-RI and sTNF-RII, respectively), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sFas and sFasL were measured in 24 patients with stable CHF (New York Heart Association functional class II/III; left ventricular ejection fraction 23.2 +/- 1.3%) and in 20 normal control subjects before and after a 12-week program of physical training in a randomized, crossover design. Functional status of patients with CHF was evaluated by using a cardiorespiratory exercise test to measure peak oxygen consumption (VO2max). RESULTS: Physical training produced a significant reduction in plasma levels of TNF-alpha (7.5 +/- 1.0 pg/ml vs. 4.6 +/- 0.7 pg/ml, p < 0.001), sTNF-RI (3.3 +/- 0.2 ng/ml vs. 2.7 +/- 0.2 ng/ml, p < 0.005), sTNF-RII (2.6 +/- 0.2 ng/ml vs. 2.3 +/- 0.2 ng/ml, p = 0.06), IL-6 (8.3 +/- 1.2 pg/ml vs. 5.9 +/- 0.8 pg/ml, p < 0.005), sIL-6R (34.0 +/- 3.0 ng/ml vs. 29.2 +/- 3.0 ng/ml, p < 0.01), sFas (5.5 +/- 0.7 ng/ml vs. 4.5 +/- 0.8 ng/ml, p = 0.05) and sFasL (34.9 +/- 5.0 pg/ml vs. 25.2 +/- 4.0 pg/ml, p < 0.05), as well as a significant increase in VO2max (16.3 +/- 0.7 ml/kg per min vs. 18.7 +/- 0.8 ml/kg per min, p < 0.001). Good correlations were found between a training-induced increase in VO2max and a training-induced reduction in levels of the proinflammatory cytokine TNF-alpha (r = -0.54, p < 0.01) and the apoptosis inducer sFasL (r = -0.57, p < 0.005) in patients with CHF. In contrast, no significant difference in circulating cytokines and apoptotic markers was found with physical training in normal subjects. CONCLUSIONS: Physical training reduces plasma levels of proinflammatory cytokines and the sFas/sFasL system in patients with CHF. These immunomodulatory effects may be related to the training-induced improvement in functional status of patients with CHF.

Adult↗

PubMed2002

Endothelial dysfunction in chronic heart failure: clinical and therapeutic implications.

Chronic heart failure is a complex clinical syndrome in which abnormal vascular endothelial function has been shown to occur at both the experimental and clinical levels. Alterations in endothelial function may contribute to the increased vasomotor tone and to the vascular remodeling process observed in patients with chronic heart failure. Reduced shear stress, increased activity of the various vasoconstricting neurohormonal systems, and increased levels of proinflammatory cytokines promote endothelial dysfunction in chronic heart failure. This article summarizes the major mechanisms implicated in the pathophysiology of abnormal endothelial function in chronic heart failure, as well as the novel therapeutic interventions aimed at reducing endothelial dysfunction in patients with the syndrome.

Journal Article↗

PubMed2002

Cytokines and anti-cytokine therapeutic approaches to chronic heart failure.

Recent investigations have shown that, in addition to neurohormonal system overactivation, another class of biologically active molecules, termed cytokines, is also overexpressed in the setting of chronic heart failure and participates actively in the progression of the syndrome. In this article, we present recent experimental and clinical data describing the pathophysiological role of cytokines in left ventricular remodeling, endothelial dysfunction, and peripheral myopathy characterizing the progression of chronic heart failure, as well as novel therapeutic approaches aimed at attenuating the deleterious effects of cytokines on the cardiovascular system.

Journal Article↗

PubMed2002

Acute haemodynamic effects of oestrogen administration in male patients with chronic heart failure.

BACKGROUND: Although there are many studies concerning the effects of long-term oestrogen administration on systemic haemodynamics in postmenopausal women, the effects of oestrogen in patients with chronic heart failure are not defined. AIM: The goal of this study was to evaluate the acute haemodynamic effects of oestrogen in male patients with chronic heart failure. METHODS AND RESULTS: We studied 15 men with advanced heart failure (NYHA II-IV, EF < 35%). A Swan-Ganz thermodilution catheter was advanced in their pulmonary artery and central haemodynamics were assessed at baseline, after placebo administration, and following 0.625 and 1.25 mg of oestrogen infusion. Simultaneously, all patients underwent limb plethysmography. Analysis of variance with repeated measures was used to compare the sequential measurements. Following oestrogen administration, right atrial, pulmonary artery and pulmonary capillary wedge pressures, as well as systemic, pulmonary and forearm vascular resistance were decreased; cardiac output, cardiac index, stroke volume, stroke volume index, stroke work index and forearm blood flow were increased. CONCLUSIONS: In male patients with chronic heart failure, acute oestrogen administration improves the indices of cardiac systolic performance and decreases pulmonary and systemic vascular resistance. These findings imply a beneficial effect of oestrogen in selected patients with chronic heart failure.

Aged↗

PubMed2002

Growth hormone administration reduces circulating proinflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy.

BACKGROUND: Recent studies have shown that an abnormal proinflammatory cytokine expression and apoptotic process contribute to adverse left ventricular remodeling and progress of chronic heart failure. This study investigates the effects of growth hormone (GH) administration on serum levels of representative proinflammatory cytokines and soluble apoptosis mediators in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy (IDC). METHODS: Serum levels of tumor necrosis factor-alpha (TNF-alpha), its soluble receptors (sTNF-RI, sTNF-RII), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), soluble Fas (sFas) and soluble Fas Ligand (sFasL) were determined (enzyme-linked immunosorbent assay method) in 10 patients with IDC (New York Heart Association class III, ejection fraction 24% +/- 2%) before and after a 3-month subcutaneous administration of 4 IU GH every other day (randomized crossover design). Peak oxygen consumption (Vo(2)max) was also used to evaluate the functional status of patients with IDC. RESULTS: Treatment with GH produced a significant reduction in serum levels of TNF-alpha (8.2 +/- 1.2 vs 5.7 +/- 1.1 pg/mL, P <.05), sTNF-RI (3.9 +/- 0.4 vs 3.2 +/- 0.3 ng/mL, P <.05), sTNF-RII (2.6 +/- 0.3 vs 2.2 +/- 0.2 ng/mL, P <.05), IL-6 (5.5 +/- 0.6 vs 4.4 +/- 0.4 pg/mL, P =.05), sIL-6R (32.7 +/- 3.0 vs 28.2 +/- 3.0 ng/mL, P <.05), sFas (4.4 +/- 0.8 vs 3.1 +/- 0.6 ng/mL, P <.05), and sFasL (34.2 +/- 11.7 vs 18.8 +/- 7.3 pg/mL, P <.01). A significant improvement was also observed in VO2max after the completion of 3 months' treatment with GH (15.0 +/- 0.8 vs 17.2 +/- 1.0 mL/kg/min, P <.05). Good correlations were found between GH-induced reduction in TNF-alpha levels and increase in VO2max (r = -0.64, P <.05) as well as between GH-induced reduction in sFasL and increase in VO2max (r = -0.56, P =.08). CONCLUSIONS: GH administration reduces serum levels of proinflammatory cytokines and soluble Fas/FasL system in patients with IDC. These immunomodulatory effects may be associated with improvement in clinical performance and exercise capacity of patients with IDC.

Adult↗

PubMed2002

Serum profiles of C-C chemokines in acute myocardial infarction: possible implication in postinfarction left ventricular remodeling.

C-C chemokines are essential factors in the recruitment and activation of leukocytes from the circulation into inflamed tissue and may play a role in ischemia-induced myocardial injury and left ventricular remodeling after acute myocardial infarction (AMI). We investigated the kinetics of three major C-C chemokines, macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and regulated on activation normally T cell expressed and secreted (RANTES), in the sera of AMI patients and correlated the findings with the severity of the disease. Serum levels of C-C chemokines were determined in 35 AMI patients by ELISA assays serially during the first week of hospitalization and 1 month after hospital admission. Patients (n = 18) with uncomplicated AMI (Killip class I) were classified as group A, patients (n = 17) with AMI complicated by heart failure manifestations (Killip classes II and III) were classified as group B, and 15 age-matched and sex-matched volunteers were used as healthy controls. A sustained increase in serum C-C chemokines was observed in both AMI groups during the 7-day hospitalization period. Peaks of these inflammatory factors were significantly higher in group B than in group A (MCP-1, 295 +/- 11 vs. 203 +/- 9 pg/ml, p < 0.01; MIP-1 alpha, 30 +/- 1 vs. 24 +/- 2 pg/ml, p < 0.05; RANTES, 32 +/- 2 vs. 16 +/- 1 ng/ml, p < 0.01) and healthy controls (MCP-1, 125 +/- 7 pg/ml, p < 0.001; MIP-1 alpha, 14 +/- 1 pg/ml, p < 0.001; RANTES, 12 +/- 1 ng/ml, p < 0.001). In group B, significant correlations were found between the peak of MCP-1 and the peak of C-reactive protein levels (r = 0.55, p < 0.02) as well as wedge pressure (r = 0.40, p < 0.05). In the same group, the peak of MIP-1 alpha levels was also significantly correlated with the peak of serum creatine kinase-myocardial band (MB) (r = 0.51, p < 0.04) and left ventricular ejection fraction (LVEF) (r = -0.45, p < 0.05). After 1 month, AMI patients (n = 14) with severe left ventricular dysfunction (LVEF < or = 35%) exhibited significantly higher levels of C-C chemokines (all p < 0.05) than the other AMI patients (n = 21) (LVEF > 35%). A significant correlation was found between MIP-1 alpha levels and left ventricular end-diastolic diameter (r = 0.47, p < 0.03) in this patient population. In conclusion, we have detected a significant elevation of major C-C chemokines during the course of AMI, with the highest levels in patients with AMI complicated by heart failure manifestations and severe left ventricular dysfunction. The elevation of these chemotactic inflammatory factors may actively contribute to the pathophysiology of the disease and the subsequent left ventricular remodeling.

Chemokine CCL2↗

PubMed2002

Left atrial functional reserve in patients with nonischemic dilated cardiomyopathy: an echocardiographic dobutamine study.

OBJECTIVE: To evaluate left atrial functional reserve in patients with chronic heart failure and nonischemic dilated cardiomyopathy (DCM). BACKGROUND: Left ventricular functional status has been investigated using echocardiographic dobutamine. METHODS: In 35 consecutive patients (29 men and 6 women; mean +/- SD age, 42.37 +/- 13.5 years), peak oxygen consumption (O(2)max) was measured; the day after, a low-dose dobutamine (5 to 10 micro g/kg/min, of 5 min each step) study was performed. Left atrial volumes at mitral valve opening, onset of left atrial systole, and mitral valve closure were measured by using two-dimensional echocardiography. Left atrial active emptying volume (LAEV) [volume at onset of atrial systole - minimal volume] was calculated, as was left atrial active emptying fraction (LAEF): [(volume at onset of atrial systole - minimal volume)/volume at onset of atrial systole] x 100. The changes (values obtained after inotropic stimulation minus those obtained at baseline) of the above-mentioned echocardiographic variables were considered as left atrial functional reserve. RESULTS: In the entire study group after dobutamine infusion, increases in LAEV (3.34 +/- 7.54 mL, p = 0.01) and LAEF (6 +/- 13.2%, p = 0.01) were observed. The changes in the above-mentioned parameters were correlated with O(2)max values (r = 0.73 and r = 0.71, respectively; p < 0.001). After inotropic stimulation, LAEV and LAEF were increased in patients with O(2)max values > 14 mL/kg/min (5.62 +/- 7.28 mL and 10.04 +/- 13.13%, respectively) and decreased in patients with O(2)max values < 14 mL/kg/min (- 1.08 +/- 6.13 mL and - 1.6 +/- 9.9%, respectively; p = 0.01 for both). CONCLUSION: Echocardiographic dobutamine can evaluate left atrial functional reserve in patients with nonischemic DCM.

Adult↗

PubMedDate not supplied

Plasma profiles of circulating granulocyte-macrophage colony-stimulating factor and soluble cellular adhesion molecules in acute myocardial infarction. Contribution to post-infarction left ventricular dysfunction.

No in vivo data exist about the relationship of circulating granulocyte-macrophage colony stimulating factor (GM-CSF) and soluble adhesion molecules ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) to the severity of acute myocardial infarction (AMI) and the pathophysiological events of post-infarction left ventricular dysfunction. We investigated the kinetics of these inflammatory mediators in the plasma of patients with AMI, and correlated the findings with the clinical severity of the disease during the first week of hospitalization as well as the degree of left ventricular dysfunction one month after the AMI. Plasma levels of inflammatory markers were determined in 41 AMI patients (all received thrombolytic treatment) by ELISA assays, serially during the first week of hospitalization and one month after hospital admission. Patients (n = 20) with uncomplicated AMI (Killip class I) were classified as group A, patients (n = 21) with AMI complicated by heart failure manifestations (Killip classes II and III) were classified as group B, while 20 age- and sex-matched volunteers were used as healthy controls. A sustained increase in GM-CSF, sICAM-1 and sVCAM-1 plasma concentrations was observed only in group B during the first week of the study. Patients from group B exhibited significantly higher levels of GM-CSF (P < 0.01), sICAM-1 (P < 0.05) and sVCAM-1 (P < 0.01) than patients from group A and the healthy controls (P < 0.001). In group B patients, significant correlations were observed between the peak of GM-CSF levels and the peak of serum creatine kinase-MB (r = 0.42; P < 0.05), white blood cell counts (r = 0.67; P < 0.001) and LVEF (r =- 0.51; P < 0.01). At one month follow-up, patients (n = 17) with severe post-infarction left ventricular dysfunction (LVEF 35%). Significant correlations were observed between GM-CSF levels and left ventricular end-diastolic volume index (r = 0.55; P < 0.001) or left ventricular end-systolic volume index (r = 0.49; P = 0.001). We have found a significant elevation of plasma GM-CSF and soluble adhesion molecules during the course of AMI, with the highest values in patients with AMI complicated by heart failure manifestations and severe left ventricular dysfunction. These monocyte-related inflammatory mediators may actively contribute to the pathophysiology of the disease and post-infarction cardiac dysfunction.

Aged↗