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BACKGROUND Heart failure is characterized by a tissue damage that progressively leads to mechanical cardiac dysfunction and remodeling. A recent investigation showed that α-1 antitripsin, an antiprotease, able to inhibit metalloproteinases, provides prognostic information about heart failure and mortality postacute myocardial infarction. Therefore, we conducted a study to establish if α-1 antitrypsin (AAT) could be considered a marker of severity of heart failure. METHODS A total of 182 heart failure patients (Group 1) were enrolled and AAT values were compared with controls (Group 2). RESULTS In Group 1 a significant increment of AAT levels respect to Group 2 was observed (P

Heart failure (HF) is considered one of the most common diseases and one of the major causes of death. The latest studies show that HF is associated with an increase in oxidative stress. The use of antioxidants as therapy is effective in animal models, but not in humans. In this review, we analyse some emerging markers related to oxidative stress, evaluating their possible use as therapeutic targets: galectin-3, a β galactoside associated with myocardial fibrosis, α1-antitrypsin, an antiprotease and lectin-like oxidized low-density-lipoprotein receptor-1, the major receptor for ox-LDL. The up-regulation of galectin-3 appears to be associated with HF, atrial fibrillation, dilated cardiomyopathy, fibrogenesis and mortality, while in other cases it seems that galectin-3 may be protective in ischaemia-reperfusion injury. Serum α1-antitrypsin protein levels may increase in the presence of high concentrations of serum proteases, which are over expressed during reperfusion. The overexpression of α1-antitrypsin or the exogenous α1-antitrypsin treatment exhibits an anti-oxidative stress role, evaluated by increased eNOS expression and by decreased MMP9 expression, implicated in HF. The cardiac lectin-like oxidized low-density-lipoprotein receptor-1 is activated by oxidative stress in ischaemia-reperfusion injury, inducing apoptosis in cardiomyocytes through the deleterious NF-kB pathway, while the administration of anti-lectin-like oxidized low-density-lipoprotein receptor-1 antibody suppresses apoptosis and reduces the extent of myocardial infarction. In conclusion, α1-antitrypsin and lectin-like oxidized low-density-lipoprotein receptor-1 seem to represent two good markers in HF and therapeutic targets, whereas galectin-3 does not.

Atherosclerosis is a systemic inflammation of the arteries characterized by atherosclerotic plaque due to the accumulation of lipids, inflammatory cells, apoptotic cells, calcium and extracellular matrix (ECM) proteins. Stable plaques present a chronic inflammatory infiltration, whereas vulnerable plaques present an ‘active’ inflammation involved in the thinning of the fibrous cap that predisposes to plaque rupture. Several complex biological cellular processes lead plaques to evolve from stable to vulnerable predisposing them to rupture and thrombosis. In this review, we analyze some emerging circulating biomarkers related to inflammation, ECM and lipid infiltration, angiogenesis, metalloproteinases and microRNA (miRNA), as possible diagnostic and prognostic indicators of plaque vulnerability.

Thyroid hormones (TH) play an important role in heart vascular system, and both hyperthyroidism and hypothyroidism are associated with altered cardiovascular system. Moreover, several evidences suggest that heart diseases trigger a reduction in cardiac tissue thyroid hormone levels.

Cardiac Troponins (cTnI, cTnT), NT-proBNP, and galectin-3 (GAL-3) mirror cardiomyocyte injury, stretch, and fibrosis. However, although these biomarkers has been thoroughly studied in marathon or ultramarathon, the effects occurring running shorter distances, as half-marathon, are less known and data are generally limited to immediately post-race evaluation. Moreover, significant variation of alpha-1 antitrypsin (AAT), an anti-protease factor with anti-inflammatory properties, has been recently observed in heart failure, but not investigated in paraphysiological settings. The aim of the study was to evaluate these biomarkers concentration and trends in trained runners before half-marathon run and during a 48-h recovery period. In 18 half-marathon runners (15 males, 46 ± 6 years), cTnI, GAL-3 (Architect, Abbott), cTnT, NT-proBNP (Cobas e411, Roche), and AAT (Abcam, Cambridge, UK) were evaluated at rest, immediately post-run, and at 24 and 48-h recovery period. cTnT, NT-proBNP, and GAL-3 transiently increased after post-race, but normalized at 24 h (GAL-3 p

Aims: We assessed the inter-relationship that exists between variations of different biochemical and hematological parameters following strenuous endurance exercise in Ironmen by using multiple factor analysis (MFA). MFA was used to estimate the associations among groups of parameters in order to identify concurrent changes in many different biochemical variables. Materials & methods: In total, 14 Ironman athletes were followed before and early after a race. MFA was applied to the parameters that showed a significant variation after the race, as we previously described in detail. Specifically, MFA standardizes data in each group and calculates the global axes (GAs), which are the linear combination of original parameters that maximize the global data variance. Results: MFA identified three global axes (GAs) as significant, explaining approximately 62% of the global data variance. The first GA contained NT-proBNP, IL-1ra, IL-6, IL-8 and the oxidative index. The second and third GAs included calcium, creatinine, potassium, uric acid, hemoglobin, hematocrit and glucose. Analysis of the first two GAs showed that changes in the oxidative index were associated with variations in IL-8 and NT-proBNP. Conclusion: Among all the variables considered, MFA evidenced a close relationship between variations in oxidative stress, IL-8 and NT-proBNP, which may have a meaning in the mechanisms related to the physiological response after strenuous acute exercise.

Background: Oxidative stress is crucial in the pathogenesis of atherosclerosis and acute myocardial infarction (AMI). Under the generic terms &ldquo, oxidative stress&rdquo, (OS), many biomarkers belonging to different pathways have been proposed. Aim: To compare the levels of recently proposed OS-related parameters in acute coronary syndromes (ACS) and stable coronary artery disease (CAD), to evaluate their effectiveness as additive risk or illness indicators of stable and acute ischemic events, and their response over time during the course of AMI. Methods: 76 ACS, 77 CAD patients, and 63 controls were enrolled in the study. Different OS-related biomarkers, including reactive oxygen metabolites (ROM), the total antioxidant capacity (OXY), nitrite/nitrate (final nitric oxide products, NOx), and Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), were evaluated. Moreover, time response during AMI course (admission, and 6, 12, 18, 24, 36, and 48 hours after, T0-T6, respectively) and correlation with traditional cardiovascular (CV) risk factors (age, gender, hypertension, diabetes mellitus, dyslipidemia, smoking habit) were also assessed. Results: Over time, ROM progressively increased while OXY and NOx decreased. Kinetics of LOX-1 during AMI shows that this biomarker boosts early during the acute event (T1 and T2) and then progressively decreases, being significantly lower from T0 to T6. Different OS-related biomarkers were differentially associated with CV risk factors and CAD or ACS presence. Conclusion: Differences in OS-related biomarkers (between groups, according to the response over time during AMI, and to the presence of CV risk factors) confirmed OS involvement in the transition from healthy status to stable CAD and ACS, although evidencing the heterogeneous nature of redox processes. In future, a multi-marker panel including different biomarkers and pathways of oxidative stress could be evaluated as an additive tool to be used in the CV prevention, diagnosis, patient stratification, and treatment.

In the study of new drug molecules for the treatment of cancer, nitric oxide has received much attention for its tumoricidal role. In addition to its direct cytotoxic effect, NO may enhance the efficiency of classical chemotherapeutic drugs, resulting in a promising strategy against tumorigenesis and tumor progression. However, the clinical therapeutic potential of NO is limited by the short half-life, the concentration, and the biological microenvironment with which it interacts. Particular attention should be paid to the concentrations, as according to some authors, low NO levels could promote the growth of cancer cells. The development of a nanoparticle-based delivery system is aimed to the selective release of NO and drugs at the target tumor site, increasing their stability and biodistribution and preserving their therapeutic dosage. This review summarizes the current knowledge of NO-based anticancer treatments and their association with chemotherapy, focusing on the benefit of using nanotechnology.

To establish whether C-reactive protein (CRP) is an independent predictor of all-cause mortality and hospitalization in chronic obstructive pulmonary disease (COPD), we followed 200 patients with COPD and 201 age- and gender -matched controls for a median time of 4.2 years (range, 0.2-5.1 years). Airflow obstruction was rated moderate if forced expiratory volume in one second (FEV(1)) was 50-69% of the predicted value, or severe if FEV(1) was50%. The CRP level was categorized as low (≤3 mg/L) or high (3 mg/L). The hazard of death was estimated by a proportional hazard regression model, using controls with low CRP as the reference category. Fifty subjects died: 41 (21%) among the COPD and 9 (4%) among the controls (p0.0001). The hazard of death in moderate COPD was not significantly higher than in the reference category, independently of the CRP level. In severe COPD with a low CRP, the hazard of death is 3.4 times higher than in the reference category (p = 0.008); in severe COPD and a high CRP it is 9.6 times higher (p0.0001). The rate of hospitalization in COPD patients with a high CRP is 1.9 times higher than in those with a low CRP [95% confidence interval (CI), 1.2-3.2]. In severe COPD, it is 6.9 times higher than in moderate COPD (95% CI, 3.8-12.7). A high CRP level is a significant amplifier of the risk of death only in severe COPD. The degree of airflow obstruction is a strong independent predictor of COPD-related outcomes.

Cytokines and thyroid hormones are involved in the biochemical changes associated to heart failure (HF).Aims of the study were to investigate: plasma circulating levels of the cytokines Interleukine-6 (IL-6) TNF alpha and C reactive protein (CRP) in patients with stable HF in relation to the severity of left ventricular dysfunction; the relationship between these inflammatory markers and thyroid hormones.One-hundred and sixty-six patients (121 males, age 64+/-12), with non-ischemic cardiomyopathy, were admitted to the Institute of Clinical Physiology for progressive deterioration of symptoms. Forty-eight healthy subjects (30 males, age range 26-75 years) were also enrolled as control group (Group N). High sensitivity (hs)-IL-6 and hs-TNFalpha were quantified using solid phase sandwich ELISA kits. Hs-CRP was measured by Immulite System.In the whole population (HF and N), the association between inflammatory markers and age resulted statistically significant only for IL-6 serum concentration (p0.001) but not for TNFalpha and CRP. IL-6 and TNFalpha were strongly higher in the HF in comparison with N (p0.001) while CRP showed a less significant difference (p0.05). Whole population showed a negative association between IL-6 and EF% and between CRP and EF% (respectively p0.01, r=-0.23; p0.05, r=0.19). Comparing normal subjects with two classes of patients, respectively with EF35% and EF35%, we clearly observed the progressive enhancement of the inflammatory markers. Considering normal subjects, patients without and with low T3 syndrome, IL-6 and TNFalpha increased progressively from normal to patients with fT32 pg/ml (p0.01 and p0.01) while CRP only respect to the group with low T3 syndrome (p0.01). The inflammatory markers were all inversely correlated with FT3 levels.Because low FT3 serum concentration represents a negative prognostic index, it is likely that impairment of T3 production and enhanced inflammation represent pathogenic mechanisms linked to HF progression.

In animal models, increased tissue receptor for advanced glycation end products and its ligands, including N-epsilon-(carboxymethyl)lysine (CML), are critically implicated in postprocedural intimal hyperplasia after balloon injury. In patients undergoing percutaneous coronary interventions with stenting, we investigated whether plasma levels of CML and the soluble form of receptor for advanced glycation end products (sRAGE) changed during poststenting follow-up.We studied 81 patients with coronary artery disease who underwent successful percutaneous coronary interventions. Plasma levels of CML and sRAGE were measured before intervention, and at 1 day and 180 days of follow-up.CML levels increased significantly at day 1 after stenting and persisted at an elevated level at 180 days (P=0.013), whereas sRAGE levels increased significantly at 180 days (P=0.011). CML levels were significantly higher in multivessel-treated patients than in single-vessel-treated patients both at 1 day and 180 days of follow-up. In addition, CML values were positively associated with the extent of stent area at 1 day and 180 days of follow-up (r=0.278, P=0.022 and r=0.315, P=0.012, respectively). In logistic regression analysis, only the extent of stent area predicted adverse clinical events at 180-day follow-up (P=0.03, odds ratio=14.25, confidence interval=1.25-162.2).This study supports the hypothesis that increased circulating levels of CML occurred in the presence of vascular injury. This persistent rise of CML could amplify an inflammatory phenomenon triggered by stent placement and thus contributes to coronary artery disease progression.

Coronary artery disease is an event of atherosclerosis characterized by a chronic vascular inflammation. Risk factors like obesity, diabetes mellitus, hypertension, smoking, hypercholesterolemia and positive family history sometimes are not sufficiently adequate to the enhancement of cardiovascular risk assessment. In the past years numerous biomarkers, like C reactive protein, cytokines and adhesion molecules, have been observed to be related to adverse cardiovascular prognosis. Recently, several studies found an association among inflammatory biomarkers and cardiovascular diseases suggesting their utility to identify the risk of an acute ischemic event and the detection of vulnerable plaques. The emerging inflammatory markers are well divided for diagnosis and prognosis and plaque instability of coronary artery disease. Some of them, the lectin-like oxidized low density lipoprotein receptor-1 can be important both in diagnosis and in the evaluation of plaque instability, other are inserted in the above reported classification. The emerging inflammatory markers in acute-phase include amyloid A, fibrinogen and pentraxin 3 while myeloperoxidase, myeloid-related protein 8/14 and pregnancy-associated plasma protein-A are recognize markers of plaque instability. Lastly, some studies demonstrated that circulating miRNAs are involved in coronary artery disease, acute myocardial infarction and heart failure.

Heart failure is a pathological condition characterized by cardiac dysfunction and neuroendocrine system activation. The aim of this study was to evaluate serum α-1 proteins in the characterization of heart failure patients. The study included 69 patients with documented heart failure disease and 44 healthy individuals. We included 12 out of 69 patients with preserved (>50%) left ventricular ejection fraction. α-1 protein levels were evaluated using routine capillary electrophoresis. Markers of inflammation, such as interleukin-6 (IL-6) and tumor necrosis factor-α, were measured with UltraSensitive ELISA Kits. C-reactive protein and brain natriuretic peptide were determined by automated assays. No difference in α-1 protein levels between patients with reduced versus preserved left ventricular ejection fraction was observed. IL-6, tumor necrosis factor-α, and C-reactive protein concentrations were significantly increased in patients with respect to the control group (P

The development of atherosclerosis is caused by the accumulation of lipid, inflammatory cytokine production, and the large amount of inflammatory cells in the arterial wall. It is now established that the presence of oxidized low-density lipoproteins (ox-LDL) has an important role in the pathogenesis of the disease. There are many scavenger receptors for ox-LDL, among which LOX-1 seems to be important for the induction of endothelial dysfunction and the other subsequent events that lead to the formation of atheromatous plaque. Our findings indicate the presence of a regulatory role induced by the presence of ox-LDL on LOX-1 through the amplification of IL-6 synthesis. This mechanism contributes to the upregulation of the ORL-1 gene expression in presence of risk factors. Many authors have shown the possibility to use LOX-1 as a good marker for the diagnosis and prognosis of coronary artery disease because it is easy to measure and more sensitive than other markers commonly used in the routine of laboratory medicine.

Myocardial tissue perfusion is not currently quantified in the clinical setting. Thus the aim of this paper is to review the quantitative information on myocardial perfusion provided by contrast echocardiography. In a circulatory model-without the capillary network interposed between injection and sampling point of contrast-the transit time of microbubbles (source of the echo contrast effect) is inversely related to absolute flow, thus providing accurate quantitation. A similar situation is represented by blood flow inside a vessel or a cardiac cavity, where, if the prerequisites for quantitation are respected, it is possible to measure blood flow by contrast echocardiography. In the coronary circulation, the transit time of contrast microbubbles varies according to their interaction with coronary microcirculation, and to the characteristics of contrast agents as flow tracers. Echo contrast agents with small microbubbles have been injected into the coronary branches of experimental animals, under both coronary autoregulation and maximal coronary dilation, providing good estimates of coronary blood flow. The accuracy of these measurements might improve when new contrast agents, with characteristics closer to those of a flow tracer, are available. If a tracer is injected before a bifurcation, and provided it mixes adequately, the amount of tracer distributed to each branch is proportional to the corresponding blood flow. A similar situation is encountered when an echo contrast agent is injected into the aortic root or into the left main coronary artery. Here, the ratio between myocardial signal intensity in the different perfusion territories reflects the corresponding ratio of blood flows. The validity of this approach has been previously demonstrated in experimental animals and validated in patients with coronary stenoses. The injection of contrast agents into the coronary circulation at baseline and under coronary hyperaemia has the potential for measuring coronary blood flow reserve. However, what is still unclear is whether contrast echo changes reflect changes in coronary blood flow (i.e. flow reserve), coronary blood volume (i.e. coronary recruitment) or both, and also whether they influence the different types of contrast agent. Finally, myocardial contrast echocardiography can provide information on the spatial distribution of myocardial perfusion, i.e. the presence, site and extent of perfused myocardium. Thus, in models where myocardial perfusion may be either present or absent, contrast echo can provide an accurate estimate of perfusion abnormalities.

Objectives: Smoking increases oxidative modi-fication of LDL, associated with lower HDL plasma levels, systemic inflammatory response and endothelial dysfunction. We tested the hy-pothesis that the risk status for coronary atherosclerosis disease (CAD) of cigarettes smokers might be identified by means of serum oxidative levels and vascular inflammation de-termination. Design and Methods: Oxidative stress levels, cytokines, and the metabolic status were investigated on 499 subjects admit-ted to our institute. The association between biomarkers and smoking habits in the pres-ence/absence of disease and with the number of vessel affected, was studied. Results: Oxidative stress and inflammatory levels (p < 0.001) were strongly induced by smoking habits. Serum values of the subjects categorised as CAD, non CAD and healthy subjects differed significantly (p < 0.001) only for the degree of oxidative stress. Glycaemia was able to affect C-reactive protein serum levels with a positive association (p < 0.05). The analysis of the study population in-dicated that serum oxidative stress levels sig-nificantly increased with increasing number of vessels affected (p < 0.01). When statistical analysis was performed separately in both smoking groups, smokers did not show any particular difference for both oxidative stress and inflammation markers between the two groups of cardiovascular patients (CAD and non CAD) and the control group, while for non smokers, the differences were evident. Conclu-sion: These findings indicate that the consid-ered biomarkers, especially oxidative stress, can be useful to predict the biological damage caused by cigarette smoking, as well as to iden-tify subjects characterised by a higher risk of cardiovascular event, but cannot evaluate the presence of disease in subjects with smoking habit.

Whether prolonged strenuous exercise performed by athletes at sea level can produce interstitial pulmonary edema is under debate. Chest sonography allows to estimate extravascular lung water, creating ultrasound lung comet-tail (ULC) artifacts. The aim of the study was to determine whether pulmonary water content increases in Ironmen ( n = 31) during race at sea level and its correlation with cardiopulmonary function and systemic proinflammatory and cardiac biohumoral markers. A multiple factor analysis approach was used to determine the relations between systemic modifications and ULCs by assessing correlations among variables and groups of variables showing significant pre-post changes. All athletes were asymptomatic for cough and dyspnea at rest and after the race. Immediately after the race, a score of more than five comet tail artifacts, the threshold for a significant detection, was present in 23 athletes (74%; 16.3 ± 11.2; P < 0.01 ULC after the race vs. rest) but decreased 12 h after the end of the race (13 athletes; 42%; 6.3 ± 8.0; P < 0.01 vs. soon after the race). Multiple factor analysis showed significant correlations between ULCs and cardiac-related variables and NH2-terminal pro-brain natriuretic peptide. Healthy athletes developed subclinical increase in pulmonary water content immediately after an Ironman race at sea level, as shown by the increased number of ULCs related to cardiac changes occurring during exercise. Hemodynamic changes are one of several potential factors contributing to the mechanisms of ULCs.

See article by Wilson et al. [9] (pages 601–607) in this issue. Hypercholesterolemia is reported to be associated both with enhanced oxidative stress, related to increased lipid peroxidation [1], and with augmented susceptibility to coronary vasoconstriction [2]. The abnormal coronary vasoreactivity is mainly attributed to endothelial dysfunction, which in hypercholesterolemic man has been demonstrated by several approaches, including coronary and forearm blood flow response to acetylcholine (ACh) [3,4], and flow-mediated dilation [5]. An increased generation of oxidized LDL is a major factor responsible for the vascular damage related to high cholesterol levels, and oxidative stress leads to increased breakdown and/or reduced bioavailability of NO in a number of experimental and clinical models [6]. F2-Isoprostanes, namely 8-epi-prostaglandin F2α (8-epi-PGF2α), have been recently proposed as reliable markers of oxidative stress in vivo [7,8]. Wilson et al. [9] in their study demonstrate that 8-epi-PGF2α causes a dose-dependent vasoconstriction in vitro, in pig coronary strips obtained from normal and hypercholesterolemic animals. Coronary vasoconstriction induced by 8-epi-PGF2α is shown to be modulated by endothelial NO, being increased after both endothelial denudation and L-NMMA administration in control animals. Hypercholesterolemic vessels (HV), in turn, show an increased coronary vasoconstriction to 8-epi-PGF2α which is comparable to that observed in normal animals following endothelium denudation, specific for 8-epi-PGF2α, not being found with other vasoconstrictor prostanoids, and is attenuated by pretreatment with l-arginine or the NO donor NOR-3. These observations suggest a tonic vasoconstrictor activity dynamically opposed by NO, with the net vasomotor effect resulting from the balance of the two systems. Furthermore, 8-epi-PGF2α in hypercholesterolemic animals … * Corresponding author. Tel.: +39-50-583-288; fax: +39-50-553-461 palombo{at}po.ifc.pi.cnr.it

Superoxide dismutase (SOD) is reported to be the major enzymatic defence against free radicals and common oxidants. EC-SOD is the only extracellular form of SOD present at a high concentration in vascular intima. The aims of the present study were to elucidate the role of EC-SOD in patients with coronary artery disease (CAD) and evaluate its association with free radicals, inflammation and with the severity of the disease. The study included 36 consecutive subjects with CAD being treated in the Institute of Clinical Physiology (33 males, 3 females) and 19 controls (16 males, 2 females). Each subject, after cardiac catheterisation and coronariography, was evaluated for serum EC-SOD activity, peroxy radicals, high-sensitive interleukin-6 (hs-IL-6), high-sensitive tumour necrosis factor (hs-TNFa) and high-sensitive C-reactive protein (hs-CRP) serum levels. The analysis of EC-SOD serum activity did not show any particular difference between patients and controls, while the serum levels of peroxy radicals, hs-IL-6 and hs-CRP showed a significant difference between the two groups (respectively: P

Sedentary aging is associated with oxidative stress and endothelial dysfunction. The aim of this study was to evaluate the relationship between long-term physical activity, plasma antioxidant status, and conduit artery endothelial function in young and older healthy men.In young (n = 16) and older athletes (n = 16) and in matched healthy sedentary subjects, endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent response to glyceryl trinitrate (GTN), 400 microg, were measured in the brachial artery from high-resolution ultrasonography. Plasma malondialdehyde (MDA) and antioxidant capacity as total oxyradical scavenging capacity (TOSC) were also evaluated.We found that FMD was lower (or =0.01) in sedentary older subjects (2.3% +/- 1.0%) as compared with older athletes (5.3% +/- 3.2%) and both sedentary (5.4% +/- 2.0%) and athletically trained (6.1% +/- 3.2%) young subjects. Sedentary older subjects showed higher (Por = .05) MDA levels and lower (P.0001) plasma antioxidant capacity as compared with the other subgroups, whereas in older athletes MDA levels and antioxidant capacity were similar to those observed in the young subgroups. In the whole group, FMD, but not GTN, was negatively related to age (r = -0.31, P.05) and directly related (Por = .01) to VO2max (r = 0.49) and TOSC against peroxyl (r = 0.69) and hydroxyl radicals (r = 0.53). In the multivariate analysis, TOSC against peroxyl radicals resulted as the most significant predictor of FMD (R2 = 0.60; P = .003).These results suggest that regular physical activity is associated with preserved antioxidant defenses and endothelial function in older individuals.

Interleukin 6 (IL‐6) may represent an early marker of inflammatory activation and may be useful to ameliorate risk stratification in patients with ischemic heart disease. The aim of this study was to verify the performance characteristics of an ultrasensitive immunoassay (Biosource International, Camarillo, CA) for high‐sensitivity (hs)‐IL‐6 measurement in comparison with hs‐R&D Systems (Abingdon, United Kingdom) and Immulite System (Diagnostic Products Corporation [DPC], Los Angeles, CA) methods in patients with ischemic heart disease. In addition, hs–C‐reactive protein (hs‐CRP) concentrations were measured, to evaluate the correlation with hs‐IL‐6 levels. We measured IL‐6 and CRP serum levels in 39 patients with ischemic heart disease and in 12 controls. Out of the 39 patients studied, 13 were affected by unstable angina, 13 by post–acute myocardial infarction (AMI) unstable angina, and 13 by stable angina. The imprecision profile and functional sensitivity were performed measuring 9 different serum pools in 10 runs. The Biosource method had the best performance characteristics as compared to the others. Mean IL‐6 level was higher in patients with unstable and post‐AMI unstable angina with respect to controls. CRP levels were elevated in patients with post‐AMI. In the whole population a high significant linear regression was observed between Biosource hs‐IL‐6 and hs‐CRP serum levels. The Biosource method for IL‐6 measurement is characterized by a high functional sensitivity that allows a better stratification of patients with ischemic heart disease. J. Clin. Lab. Anal. 19:110–114, 2005. © 2005 Wiley‐Liss, Inc.

In the present study we assessed the effect of physical training on Laser Doppler skin flux (LDF) and nitric oxide (NO) release, before and after 3 min of brachial artery occlusion. To this end we performed laser Doppler measurements and the venous plasma assay of nitrite/nitrate (NOx) on 10 sedentary healthy subjects and 10 endurance athletes. The sedentary control subjects had lower basal and post reperfusion levels of NOx as compared to athletes (mean +/- SE: 27.8 +/- 3.5 vs. 33.2 +/- 3.4, 48.6 +/- 7.9 vs. 60.1 +/- 10.1 micromol/L; p < 0.05). LDF at baseline was not significantly different in the two groups (157.5 +/- 7.9 and 176.64 +/- 26.7 PU for sedentary subjects and athletes, respectively) while post ischemic LDF was significantly lower in nonathletic subjects than in athletes (209.9 +/- 13 and 343.8 +/- 21.3 PU, p < 0.001). In both groups the hyperaemic stimulus significantly increased LDF and NOx levels (p < 0.01 and p < 0.05, respectively). The flow reserve, estimated as peak/basal LDF, was significantly lower in control subjects than in athletes (1.34 +/- 0.2 and 2.32 +/- 0.9, respectively, p < 0.01). In athletes, as opposed to sedentary subjects, a direct correlation was found between plasma NOx concentration and LDF both in basal conditions (r = 0.92; p < 0.001), and during hyperaemia (r = 0.84; p < 0.01). In conclusion, compared to sedentary subjects, athletes had an enhanced nitric oxide release. Hyperaemia increased LDF and nitric oxide levels both in sedentary subjects and in athletes.

Sedentary aging is associated with endothelial dysfunction and nitric oxide (NO) impairment. The aim of the present study was to assess the effects of regular physical exercise on nitrite/nitrate (NOx) concentrations and microcirculatory function in older men compared with young individuals. We measured NOx plasma concentrations and baseline and stimulated skin blood flow (SBF) by laser Doppler flowmetry in 39 male athletes [range, 22–72 years; maximal oxygen consumption (VO2max), 60.0±4.7 ml·min-1·kg of body weight-1 (mean±S.D.)] and 45 age- and sex-matched sedentary controls (VO2max, 38.0±7.1 ml·min-1·kg of body weight-1). NOx concentrations were higher in athletes than in controls (50.4±16.3 compared with 39.0±15.4 µmol/l; P0.30, P

In biological systems there is a balance between the production and neutralization of reactive oxygen species (ROS). This balance is maintained by the presence of natural antioxidants and antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase. The enhancement of lipid peroxidation or the decrease of antioxidant protection present in metabolic diseases or bad lifestyle can induce endothelial dysfunction and atherosclerosis. Clinical studies have shown that oxidative stress can increase ROS reducing the formation of antioxidant defences, especially in subjects with coronary artery disease (CAD). Some observation indicated that in the early stages of the disease there is a homeostatic up-regulation of the antioxidant enzyme system in response to increased free radicals to prevent vascular damage. As soon as free radicals get to chronically elevated levels, this compensation ceases. Therefore, SOD and the other enzymes may represent a good therapeutic target against ROS, but they are not useful markers for the diagnosis of CAD. In conclusion antioxidant enzymes are reduced in presence of metabolic disease and CAD. However the existence of genes that promote their enzymatic activity could contribute to create new drugs for the treatment of damage caused by metabolic diseases or lifestyle that increases the plasma ROS levels.

The bound of thyroid stimulating hormone (TSH) to its receptor elevates intracellular cAMP concentration that accounts for most of the biological actions of TSH. The presence and the patho-physiological role of a TSH receptor (TSHR) in heart is not yet clear. Understanding this question is important in the clinical use of recombinant human TSH (rhTSH) of patients with thyroid cancer. We investigate the acute effect of rhTSH in the Langendorff-perfused rat heart in relation with its receptor function. Compared to control group, no change in the hemodynamic parameters was observed in rat heart perfused with TSH. Western-blot of TSHR was performed evidencing the presence of the receptor and an increased level in cAMP was observed after thirty minute TSH perfusion. In conclusion the role of TSHR in rat heart seems to be marginal, reinforcing the idea of the cardiovascular safety of administered rhTSH in thyroid patients.

The purpose of this study was to detect myocardial perfusion defects as a result of coronary occlusion and myocardial reperfusion after thrombolysis with intravenous (i.v.) administration of the echo contrast agent BR1 (Bracco Research, Switzerland), which consists of microbubbles (median diameter 2.5 microm) containing sulfur exafluoride in a phospholipidic shell. To generate a coronary thrombosis, a copper coil was advanced into the left circumflex coronary artery in eight anesthetized dogs with opened chest cavities. Coronary occlusion occurred 18 +/- 10 minutes after the insertion of the coil and was documented both by an electromagnetic flow meter (as zero blood flow) and by radiolabeled microspheres (as myocardial perfusion defect). After 2 hours of occlusion, streptokinase was infused i.v.; reperfusion was documented by both the flow-meter and microspheres. Left ventricular cavity enhancement was apparent after all contrast injections. Peak cavity intensity did not increase with dose and was not affected by signal processing (suggesting signal saturation), whereas the duration of contrast effect significantly increased with the dose (from 26 +/- 16 to 147 +/- 74 seconds). Myocardial contrast intensity also increased after contrast (from 15 +/- 12 to 21 +/- 18 gray level/pixel, p0.001). Contrast echo detected myocardial perfusion defects (corresponding to 17% +/- 11% of LV cross-sectional area) in all the injections performed during coronary occlusion and detected myocardial reperfusion with a sensitivity of 50% versus microspheres. The extent of perfusion defects by contrast echo showed a good correlation with microspheres (r = 0.73). Myocardial reperfusion was not detected by changes in heart rate, aortic pressure, pulmonary arterial pressure, cardiac output, left ventricular fractional area change, or wall-motion score index. Hemodynamic parameters were not affected by contrast injections. Thus, the i.v. administration of BR1 allows us to accurately detect myocardial perfusion defects during coronary occlusion and, to a lesser extent, myocardial reperfusion after thrombolysis.