The Role of Oxidative Stress and Inflammatory Parameters in Heart Failure.

Heart failure (HF) remains a major medical and social problem. The NT-pro-brain natriuretic peptide (NT-proBNP) and its active form, brain-type natriuretic peptide (BNP), in a simple blood test are the gold-standard biomarkers for HF diagnosis. However, even good biomarkers such as natriuretic peptides fail to predict all the risks associated with HF due to the diversity of the mechanisms involved. The pathophysiology of HF is determined by numerous factors, including oxidative stress, inflammation, neuroendocrine activation, pathological angiogenesis, changes in apoptotic pathways, fibrosis and vascular remodeling. High readmission and mortality rates prompt a search for new markers for the diagnosis, prognosis and treatment of HF. Oxidative-stress-mediated inflammation plays a crucial role in the development of subsequent changes in the failing heart and provides a new insight into this complex mechanism. Oxidative stress and inflammatory biomarkers appear to be a promising diagnostic and prognostic tool in patients with HF. This systematic review provides an overview of the current knowledge about oxidative stress and inflammation parameters as markers of HF.

Ceruloplasmin as Redox Marker Related to Heart Failure Severity.

This study examined ceruloplasmin levels in patients with HFrEF, depending on cardiopulmonary exercise testing (CPET) parameters; a correlation was found between ceruloplasmin (CER) and iron and hepatic status, inflammatory and redox biomarkers. A group of 552 patients was divided according to Weber's classification: there were 72 (13%) patients in class A (peak VO2 > 20 mL/kg/min), 116 (21%) patients in class B (peak VO2 16-20 mL/kg/min), 276 (50%) patients in class C (peak VO2 10-15.9 mL/kg/min) and 88 (16%) patients in class D (peak VO2 < 10 mL/kg/min). A higher concentration of CER was found in patients with peak VO2 < 16 mL/kg/min and VE/CO2 slope > 45 compared to patients with VE/CO2 slope < 45 (escectively CER 30.6 mg/dL and 27.5 mg/dL). A significantly positive correlation was found between ceruloplasmin and NYHA class, RV diameter, NT-proBNP, uric acid, total protein, fibrinogen and hepatic enzymes. CER was positively correlated with both total oxidant status (TOS), total antioxidant capacity (TAC) and malondialdehyde. A model constructed to predict CER concentration indicated that TOS, malondialdehyde and alkaline phosphatase were independent predictive variables (R2 0.14, p < 0.001). CER as a continuous variable was an independent predictor of pVO2 ≤ 12 mL/kg/min after adjustment for sex, age and BMI. These results provide the basis of a new classification to encourage the determination of CER as a useful biomarker in HFrEF.

Oxidative Stress Markers in Hypertrophic Cardiomyopathy.

Background and Objectives: Hypertrophic cardiomyopathy (HCM) depends on the primary impairment of sarcomeres, but it can also be associated with secondary alterations in the heart related to oxidative stress. The present study aimed to examine oxidative-antioxidant disturbances in patients with HCM compared with control individuals. Materials and Methods: We enrolled 52 consecutive HCM patients and 97 controls without HCM. The groups were matched for age, body mass index, and sex. Peripheral blood was collected from all patients to determine the total antioxidant capacity (TAC), total oxidant status (TOS), lipid hydroperoxide (LPH), and malondialdehyde (MDA). The oxidative stress index (OSI) was defined as the ratio of the TOS level to the TAC level. Results: The median age was 52 years, and 58.4% were female. The area under the curve (AUC) indicated good predictive power for the TAC and TOS [AUC 0.77 (0.69-0.84) and 0.83 (0.76-0.90), respectively], as well as excellent predictive power for the OSI [AUC 0.87 (0.81-0.93)] for HCM detection. Lipid peroxidation markers also demonstrated good predictive power to detect HCM patients [AUCLPH = 0.73, AUCMDA = 0.79]. Conclusions: The TOS, the TAC, LPH levels, and MDA levels have good predictive power for HCM detection. The holistic assessment of oxidative stress by the OSI had excellent power and could identify patients with HCM.

Whole-Body Cryotherapy Decreases the Levels of Inflammatory, Oxidative Stress, and Atherosclerosis Plaque Markers in Male Patients with Active-Phase Ankylosing Spondylitis in the Absence of Classical Cardiovascular Risk Factors.

OBJECTIVE: The aim of the study was to estimate the impact of whole-body cryotherapy (WBC) on cardiovascular risk factors in patients with ankylosing spondylitis (AS). MATERIAL AND METHODS: We investigated the effect of WBC with subsequent kinesiotherapy on markers of inflammation, oxidative stress, lipid profile, and atherosclerosis plaque in male AS patients (WBC group). To assess the disease activity, the BASDAI and BASFI were also calculated. The results from the WBC group were compared with results from the kinesiotherapy (KT) group. RESULTS: The results showed that in the WBC group, the plasma hsCRP level decreased without change to the IL-6 level. The ICAM-1 level showed a decreasing tendency. The CER concentration, as well as the BASDAI and BASFI, decreased in both groups, but the index changes of disease activity were higher in the WBC than KT patients. Additionally, in the WBC group, we observed a decrease in oxidative stress markers, changes in the activity of some antioxidant enzymes and nonenzymatic antioxidant parameters. In both groups, the total cholesterol and LDL cholesterol, triglycerides, sCD40L, PAPP-A, and PLGF levels decreased, but the parameter changes were higher in the WBC group. CONCLUSION: WBC appears to be a useful method of atherosclerosis prevention in AS patients.

[The influence of methionine and vitamin E on oxidative stress in rats' liver exposed to sodium fluoride] / Wplyw metioniny i witaminy E na stres oksydacyjny oceniany w watrobie szczurów narazonych na dzialanie fluorku sodu

BACKGROUND: Fluorine influences many processes occurring in the organism. Controversies over the evaluation of the biological effects of this substance are due to a small difference between tolerable and toxic fluorine doses. One of the main mechanisms of the fluorine toxic action is its ability to induce oxidative stress via reactive oxygen species generation and antioxidant defense system impairment. It is important to evaluate possible interactions between fluorine and other substances that may increase or decrease its toxicity. MATERIAL AND METHODS: The study lasted for 35 days. Twenty-four rats were divided into 4 groups: the control, with sodium fluoride (NaF) in the diet, with sodium fluoride, methionine and vitamin E (NaF+M+E) in the diet, with sodium fluoride and vitamin E (NaF+E) in the diet. The biochemical analysis conducted in animal liver homogenates included determination of activities of: total superoxide dismutase (t-SOD), superoxide dismutase with copper and zinc (CuZnSOD), superoxide dismutase with manganese (MnSOD), glutathione peroxidase (GPX), catalase (CAT), glutathione reductase (GR), glutathione S-transferase (GST) and the malondialdehyde (MDA) concentration. RESULTS: The activities of CuZn- SOD, GPX, CAT and MDA concentration were changed significantly. There were no differences in the activities of t-SOD, MnSOD, GR and GST among the experiment. CONCLUSIONS: In the conducted experiment, the run-out of enzymatic protection of liver by decreasing of the activities of antioxidant enzymes (CAT and GPX) and increasing the MDA concentration in NaF group was observed. The addition of vitamin E and methionine does not significantly stimulate the enzymatic antioxidant system, however, it causes of MDA concentration decreases. Med Pr 2018;69(4):403­412

Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers.

N-Acetylcysteine (NAC) could be included in protocols designed for the treatment of lead toxicity. Therefore, in this study, we decided to investigate the influence of NAC administration on homocysteine (Hcy) levels, oxidative damage to proteins, and the levels of iron (Fe), transferrin (TRF), and haptoglobin (HPG) in lead (Pb)-exposed workers. The examined population (n = 171) was composed of male employees who worked with Pb. They were randomized into four groups. Workers who were not administered any antioxidants, drugs, vitamins, or dietary supplements were classified as the reference group (n = 49). The remaining three groups consisted of workers who were treated orally with NAC at three different doses (1 × 200, 2 × 200, or 2 × 400 mg) for 12 weeks. After the treatment, blood Pb levels significantly decreased in the groups receiving NAC compared with the reference group. The protein concentration was not affected by NAC administration. In contrast, Hcy levels significantly decreased or showed a strong tendency toward lower values depending on the NAC dose. Levels of the protein carbonyl groups were significantly decreased in all of the groups receiving NAC. Conversely, glutamate dehydrogenase activity was significantly elevated in all of the groups receiving NAC, while the level of protein thiol groups was significantly elevated only in the group receiving 200 mg of NAC. Treatment with NAC did not significantly affect Fe and TRF levels, whereas HPG levels showed a tendency toward lower values. Treatment with NAC normalized the level of Hcy and decreased oxidative stress as measured by the protein carbonyl content; this effect occurred in a dose-dependent manner. Moreover, small doses of NAC elevated the levels of protein thiol groups. Therefore, NAC could be introduced as an alternative therapy for chronic Pb toxicity in humans.

Effects of Propofol on Oxidative Stress Parameters in Selected Parts of the Brain in a Rat Model of Parkinson Disease.

INTRODUCTION: Propofol is an intravenous sedative-hypnotic agent that is commonly used to induce and maintain general anaesthesia. This drug has antioxidant properties, which are partly caused by a phenolic structure similar to α-tocopherol. The present study aimed to evaluate the effect of propofol on the level of oxidative stress biomarkers in the frontal cortex, striatum, thalamus, hippocampus and cerebellum in rats with experimental Parkinson's disease (PD). MATERIAL/METHODS: The experiment was performed on 24 male Wistar rats assigned to the following groups: 1 - control; 2 - PD; 3 - PD with propofol. The dopaminergic systems were damaged with 6-hydroxydopamine (6-OHDA) administered to each lateral ventricle (2x15 µg/5 µl). 60 mg/kg of propofol was later given to the 8-week-old rats intraperitoneally. The activities of superoxide dismutase (SOD) and its enzymes Cu/ZnSOD and MnSOD, together with the malondialdehyde (MDA) concentration, total oxidative status (TOS) and total antioxidant capacity (TAC), were measured. RESULTS: In the 2nd group, a significant increase in MDA concentration in the striatum, hippocampus and thalamus, and an increase of TOS in the striatum, thalamus and cerebellum were noted, along with a TAC decrease in the cortex, striatum and thalamus. Propofol caused a significant decrease in MDA levels in the cortex, striatum, hippocampus and thalamus, and a decrease in TOS levels in the cortex, striatum and cerebellum, with increased TAC in all evaluated structures. CONCLUSIONS: A shortage of natural antioxidants is observed in PD, along with an increase in pro-oxidants in many brain areas. Propofol inhibits oxidative stress in the brain, which shows its neuroprotective properties against oxidative damage.

Influence of propofol on oxidative-antioxidative system parameters in peripheral organs of rats with Parkinson disease.

Propofol (2,6-diisopropylphenol) is a popular anaesthetic agent with antioxidant properties. The aim of the study was to assess the oxidant-antioxidant system parameters of particular organs (liver, kidney, heart, and lungs) in response to propofol administered to rats with Parkinson's disease and to healthy ones. The experiment was performed using 32 Wistar rats divided into four groups (8 rats each). The groups were as follows: 1 control, 2 Parkinson's disease, 3 control with propofol, 4 Parkinson's disease with propofol. Propofol was administered at a dose of 60 mg/kg body weight/IP, 60 minutes before decapitation. Animals were sacrificed and livers, kidneys, hearts and lungs were obtained for further biochemical analyses. The concentration of malondialdehyde (MDA), glutathione reductase (GR) activity, glutathione peroxidase (GPx) activity, glutathione S-transferase (GST) activity and catalase (CAT) activity were determined. In group 4 compared to group 2 there was observed a significant decrease in the MDA level in liver (71%), kidneys (51%) and heart (12%), increased GR activity in lungs (48%) and heart (34%), and increased CAT activity in liver (104%). In group 3 compared to group 1 there was a significant decrease in MDA level in kidneys (67%) and lungs (14%) and increased GR activity in heart (31%), liver (29%) and lungs (21%). Propofol can prevent or reduce damage caused by reactive oxygen species (ROS) by stimulating activity of antioxidative enzymes and inhibiting lipid peroxidation. Additionally, the response of tissues to administered propofol is different in Parkinson's disease and in healthy individuals.

MOLECULAR EFFECTS OF AMINE DERIVATIVES OF PHENOTHIAZINE ON CANCER CELLS C-32 AND SNB-19 IN VITRO.

Cancer therapy is challenging for scientists because of low effectiveness of so far existing therapies (especially in case of great invasiveness and advanced tumor stage). Such need for new drug development and search for more efficient new findings in therapeutical applications is therefore still valid. There are also conducted studies on modifying so far existing drugs and their new methods of usage in oncology practice. One of them is phenothiazine and its derivatives which are used in psychiatric treatment for years. They also exhibit antiprion, antiviral, antibacterial and antiprotozoal properties. Cytotoxic activity, influence on proliferation, ability to induce apoptosis suggest also a possibility of phenothiazine derivatives usage in cancer cells termination. The aim of our the study was to evaluate the influence of two amine derivatives of phenothiazine on cancer cells in vitro. Amelanotic melanoma C-32 cell line (ATCC) and glioma SNB-19 cells (DSMZ) were used in this study and two derivatives were analyzed. In view of examined substances tumor potential toxicity cells proliferation and viability exposed to phenothiazine derivatives were established. Cell cycle regulatory genes expression (TP53 and CDKN1A), S-phase marker--H3 gene and intracellular apoptosis pathway genes (BAX, BCL-2) were analyzed using RT-QPCR method. The influence of examined derivatives on total cell oxidative status (TOS), total antioxidative status (TAS), malondialdehyde concentration (MDA) and superoxide dismutase activity (SOD) were analyzed. As a result, examined phenothiazine derivatives cytotoxic action on C-32 and SNB-19 and also cells proliferation inhibition were determined. Cell cycle regulatory genes (TP53, CDKN1A) expression and protein products of genes involved in mitochondial apoptosis pathway (BAX, BCL-2) expression are changed by the presence of phenothiazine derivatives during culturing. There were also noted small changes in redox potential in cells exposed to two mentioned phenothiazine derivatives.

[Fetuin-A and its role in important processes in organism. From nanobacteries to nanoparticles. Attempt to summarize available information]. / Fetuina-A i jej rola w kluczowych procesach zachodzacych w organizmie. Od nanobakterii do nanoczasteczki. Próba podsumowania dostepnych informacji.

Fetuina-A, protein discovered in the fifties of the twentieth century, is intensively investigated recently as a participant in many intracellular process. The aim of this article is to summarize, comment and order previous knowledge on it, in anticipation of the publication the result of further research, which could be very important in diagnostic and treatment many illness.

Oxidative stress markers and C-reactive protein are related to severity of heart failure in patients with dilated cardiomyopathy.

BACKGROUND: The aim of study was to determine relationships between functional capacity (NYHA class), left ventricle ejection fraction (LVEF), hemodynamic parameters, and biomarkers of redox state and inflammation in patients with dilated cardiomyopathy (DCM). METHODS: DCM patients (n = 109, aged 45.97 ± 10.82 years), NYHA class IIV, and LVEF 2.94 ± 7.1% were studied. Controls comprised age-matched healthy volunteers (n = 28). Echocardiography and right heart catheterization were performed. Serum activities of superoxide dismutase isoenzymes (MnSOD and CuZnSOD), concentrations of uric acid (UA), malondialdehyde (MDA), and C-reactive protein (hs-CRP) were measured. RESULTS: MnSOD, UA, hs-CRP, and MDA were significantly higher in DCM patients compared to controls. Except MDA concentration, above parameters were higher in patients in III-IV NYHA class or with lower LVEF. hsCRP correlated with of MnSOD (P < 0.05) and CuZnSOD activity (P < 0.01). Both isoenzymes positively correlated with mPAP and pulmonary capillary wedge pressure (MnSOD, resp., P < 0.01 and P < 0.05 and CuZnSOD P < 0.05; P < 0.05). UA positively correlated with MnSOD (P < 0.05), mPAP (P < 0.05), and PVRI (P < 0.05). The negative correlation between LVEF and UA (P < 0.01) was detected. CONCLUSION: There are relationships among the severity of symptoms of heart failure, echocardiographic hemodynamic parameters, oxidative stress, and inflammatory activation. Increased MnSOD activity indicates the mitochondrial source of ROS in patients with advanced heart failure.

Neopterin and beta-2 microglobulin relations to immunity and inflammatory status in nonischemic dilated cardiomyopathy patients.

BACKGROUND: The aim of the study was to assess the relationships among serum neopterin (NPT), ß2-microglobulin (ß2-M) levels, clinical status, and endomyocardial biopsy results of dilated cardiomyopathy patients (DCM). METHODS: Serum NPT and ß-2 M were determined in 172 nonischaemic DCM patients who underwent right ventricular endomyocardial biopsy and 30 healthy subjects (ELISA test). The cryostat biopsy specimens were assessed using histology, immunohistology, and immunochemistry methods (HLA ABC, HLA DR expression, CD3 + lymphocytes, and macrophages counts). RESULTS: The strong increase of HLA ABC or HLA DR expression was detected in 27.2% patients-group A-being low in 72.8% patients-group B. Neopterin level was increased in patients in group A compared to healthy controls 8.11 (4.50-12.57) versus 4.99 (2.66-8.28) nmol/L (P < 0.05). ß-2 microglobulin level was higher in DCM groups A (2.60 (1.71-3.58)) and B (2.52 (1.51-3.72)) than in the control group 1.75 (1.28-1.96) mg/L, P < 0.001. Neopterin correlated positively with the number of macrophages in biopsy specimens (P < 0.05) acute phase proteins: C-reactive proteins (P < 0.05); fibrinogen (P < 0.01); and NYHA functional class (P < 0.05) and negatively with left ventricular ejection fraction (P < 0.05). CONCLUSIONS: Neopterin but not ß-2 microglobulin concentration reflected immune response in biopsy specimens. Neopterin correlated with acute phase proteins and stage of heart failure and may indicate a general immune and inflammatory activation in heart failure.

The influence of beta-carotene on homocysteine level and oxidative stress in lead-exposed workers.

BACKGROUND: Oxidative stress is involved in lead toxicity. This suggests that some antioxidants may play a role in the treatment of lead poisoning. In the light of this, the aim of the study was to determine whether beta-carotene administration reduces oxidative stress and homocysteine level in workers chronically exposed to lead. MATERIAL AND METHODS: The exposed population included healthy male workers exposed to lead who were randomly divided into 2 groups (mean blood lead level ca. 44 microg/dl). Workers in the 1st group (N = 49, reference group) had no antioxidants, drugs, vitamins or dietary supplements administered, while workers in the 2nd group (N = 33) had beta-carotene administered in a dose of 10 mg per day for 12 weeks. Biochemical analysis included markers of lead-exposure and the level of malondialdehyde (MDA), an oxidative stress biomarker. We also measured the level of homocysteine (Hcy) and thiol groups as well as the activity of superoxide dismutase (SOD) and its isoenzyme EC-SOD in serum. RESULTS: After supplementation, the level of MDA significantly decreased, compared to baseline, by 16%, and to the reference group. When compared to the reference group, Hcy level was also significantly decreased. However, the level of thiol groups was significantly higher after supplementation with beta-carotene compared to the reference group. Analogically, the activity of SOD and EC-SOD was significantly higher compared to the baseline and to the reference group. CONCLUSIONS: Despite some controversies over antioxidant properties of beta-carotene, our results indicate that its antioxidant action could provide some beneficial effects in lead poisoning independent of chelation.

Association of NT-proBNP and sST2 with Left Ventricular Ejection Fraction and Oxidative Stress in Patients with Stable Dilated Cardiomyopathy.

The aim of this study was to analyze the relationship between levels of sST2, NT-proBNP and oxidative stress markers in patients with reduced ejection fraction (HFrEF) due to non-ischemic cardiomyopathy. A total of 88 patients with HFrEF were divided into four groups based on left ventricular ejection fraction (≤25% and >25%) and NYHA functional class (group 1-LVEF > 25% and NYHA class I or II; group 2-LVEF > 25% and NYHA class III or IV; group III-LVEF ≤ 25% and NYHA class I or II; group IV-LVEF ≤ 25% and NYHA class III or IV). In 39 (44.32%) patients LVEF was reduced below 25%, and 22 of them (56.41%) were in NYHA functional class III/IV. Of the 49 (55.68%) patients with LVEF ≥ 25%, only 18.37% were in NYHA functional class III/IV (p < 0.001). Patients with LVEF ≥ 25% had lower levels of NT-proBNP, total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI). The levels of NT-proBNP but not sST-2 correlated positively with NYHA functional class (p < 0.001) and negatively with LVEF (p < 0.001). The levels of sST-2 were associated with increased TAC (p = 0.009) and uric acid (p = 0.040). These findings indicate that only NT-proBNP was related to the severity of heart failure, whereas sST2 correlated with total antioxidant capacity. Therefore, in stable patients with HFrEF due to dilated cardiomyopathy, sST2 may be an additional biomarker reflecting the redox status, but not the severity of heart failure.

Ceruloplasmin, Catalase and Creatinine Concentrations Are Independently Associated with All-Cause Mortality in Patients with Advanced Heart Failure.

The role of oxidative/antioxidative system imbalances in advanced heart failure (HF) has not been fully investigated. The aim of this study was to identify factors associated with one-year mortality in patients with advanced HF, with particular emphasis on oxidative/antioxidative balance parameters. We analyzed 85 heart transplant candidates who were hospitalized at our institution for right heart catheterization. Ten milliliters of coronary sinus blood was collected to measure oxidative/antioxidative markers. The median age was 58 (50-62) years, and 90.6% of them were male. The one-year mortality rate was 40%. Multivariable logistic regression analysis revealed that ceruloplasmin (OR = 1.342 [1.019-1.770], p = 0.0363; per unit decrease), catalase (OR = 1.053 [1.014-1.093], p = 0.0076; per unit decrease), and creatinine (OR = 1.071 [1.002-1.144], p = 0.0422; per unit increase) were independently associated with one-year mortality. Ceruloplasmin, catalase, and creatinine had areas under the curve of 0.9296 [0.8738-0.9855], 0.9666 [0.9360-0.9971], and 0.7682 [0.6607-0.8756], respectively. Lower ceruloplasmin and catalase in the coronary sinus, as well as higher creatinine in peripheral blood, are independently associated with one-year mortality in patients with advanced HF. Catalase and ceruloplasmin have excellent prognostic power, and creatinine has acceptable prognostic power, allowing the distinction of one-year survivors from nonsurvivors.

The Impact of Whole-Body Cryotherapy on Endothelium Parameters in Patients with Ankylosing Spondylitis.

BACKGROUND: The aim of the study was to assess the effect of whole-body cryotherapy (WBC) with subsequent exercise training (WBC group) or exercise-only training (ET group) on endothelium inflammation parameters in patients with ankylosing spondylitis (AS). METHODS: The WBC procedure lasted 3 min, and exercise training consisted of one 60 min session a day, which was the same in each group. The ET group was compared to the WBC group. Endothelium (high-sensitivity C-reactive protein (hsCRP), soluble P-Selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), neopterin), and oxidative stress (lipid hydroperoxide (LHP), protein sulfhydryl (PSH), lipofuscin, paraoxonase-1(PON-1), and albumin) parameters were estimated 1 day before and 1 day after the completion of the study. RESULTS: A significant decrease in hsCRP, sP-Selectin, sVCAM-1, and neopterin concentrations was observed in the WBC group after the treatment. After the treatment, in both groups, LHP and lipofuscin levels and PON-1 activity decreased significantly. The observed drop in these parameters was higher in the WBC group compared to the ET group. Albumin concentration increased in the WBC group after treatment. CONCLUSION: Procedures of WBC have a beneficial effect on endothelium parameters in AS patients; therefore, this method can be applied in the treatment of this group of patients.

The Impact of Pharmacotherapy for Heart Failure on Oxidative Stress-Role of New Drugs, Flozins.

Heart failure (HF) is a multifactorial clinical syndrome involving many complex processes. The causes may be related to abnormal heart structure and/or function. Changes in the renin-angiotensin-aldosterone system, the sympathetic nervous system, and the natriuretic peptide system are important in the pathophysiology of HF. Dysregulation or overexpression of these processes leads to changes in cardiac preload and afterload, changes in the vascular system, peripheral vascular dysfunction and remodeling, and endothelial dysfunction. One of the important factors responsible for the development of heart failure at the cellular level is oxidative stress. This condition leads to deleterious cellular effects as increased levels of free radicals gradually disrupt the state of equilibrium, and, as a consequence, the internal antioxidant defense system is damaged. This review focuses on pharmacotherapy for chronic heart failure with regard to oxidation-reduction metabolism, with special attention paid to the latest group of drugs, SGLT2 inhibitors-an integral part of HF treatment. These drugs have been shown to have beneficial effects by protecting the antioxidant system at the cellular level.

The Utility of Pentraxin and Modified Prognostic Scales in Predicting Outcomes of Patients with End-Stage Heart Failure.

Risk stratification is an important element of management in patients with heart failure (HF). We aimed to determine factors associated with predicting outcomes in end-stage HF patients listed for heart transplantation (HT), with particular emphasis placed on pentraxin-3 (PXT-3). In addition, we investigated whether the combination of PTX-3 with the Heart Failure Survival Score (HFSS), the Seattle Heart Failure Model (SHFM), or the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) improved the prognostic strength of these scales in the study population. We conducted a prospective analysis of 343 outpatients with end-stage HF who accepted the HT waiting list between 2015 and 2018. HFSS, SHFM, and MAGGIC scores were calculated for all patients. PTX3 was measured by sandwich enzyme-linked immunosorbent assay with a commercially available kit. The endpoints were death, left ventricular assist device implantation, and HT during the one-year follow-up. The median age was 56 (50−60) years, and 86.6% were male. During the follow-up period, 173 patients reached the endpoint. Independent risk factors associated with outcomes were ischemic etiology of HF [HR 1.731 (1.227−2.441), p = 0.0018], mean arterial pressure (MAP) [1.026 (1.010−1.042), p = 0.0011], body mass index (BMI) [1.055 (1.014−1.098), p = 0.0083], sodium [1.056 [(1.007−1.109), p = 0.0244] PTX-3 [1.187 (1.126−1.251, p < 0.0001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) [HR 1.004 (1.000−1.008), p = 0.0259]. The HFSS-PTX-3, SHFM-PTX-3 and MAGGIC-PTX-3 scores had significantly higher predictive power [AUC = 0.951, AUC = 0.973; AUC = 0.956, respectively] than original scores [AUC for HFSS = 0.8481, AUC for SHFM = 0.7976, AUC for MAGGIC = 0.7491]. Higher PTX-3 and NT-proBNP concentrations, lower sodium concentrations, lower MAP and BMI levels, and ischemic etiology of HF are associated with worse outcomes in patients with end-stage HF. The modified SHFM-PTX-3, HFSS-PTX-3, and MAGGIC-PTX-3 scores provide effective methods of assessing the outcomes in the analyzed group.

Levels of TNF-α and Soluble TNF Receptors in Normal-Weight, Overweight and Obese Patients with Dilated Non-Ischemic Cardiomyopathy: Does Anti-TNF Therapy Still Have Potential to Be Used in Heart Failure Depending on BMI?

Background. We sought to measure the levels of adipokines, TNF-α and soluble receptors (sTNFr1, sTNFr2) in heart failure patients with reduced ejection fraction (HFrEF) due to non-ischemic cardiomyopathy (nDCM). Methods. A total of 123 patients with HFrEF due to nDCM were divided into three groups according to BMI: 34 (27.6%) normal weight, 56 (45.5%) overweight and 33 (26.8%) obese. A six-minute walk test, echocardiography and right heart catheterization were performed. Serum concentrations of adiponectin, leptin, NT-proBNP, blood hemoglobin, sodium, creatinine, ALAT, AspAT, bilirubin, CRP, lipids, TNF-α, sTNFr1 and sTNFr2 receptors were measured. Results. Obese patients had the lowest NT-proBNP concentrations, significantly higher leptin levels and higher leptin/adiponectin ratios. The concentration of sTNFr1 was higher in normal-weight patients. In all groups, TNF-α concentrations correlated positively with sTNFr1 (p < 0.001). Higher levels of sTNFr1 were associated with higher sTNFr2 (p < 0.001) and CRP (p < 0.001). Moreover, the concentration of sTNFr2 positively correlated with CRP (p < 0.05) and adiponectin (p < 0.001). Levels of TNF-α were not associated with elevated CRP. Conclusion: This study demonstrated that changes in the concentrations of TNF and its receptors differ between groups of patients with different BMI. These findings suggest that the effective use of anti-TNF therapy is dependent not only on BMI, but also on concentrations of TNF-α receptors and other laboratory parameters.

The assessment of lipid peroxidation products and the activity of superoxide dismutase in patients with heart failure.

The study concerns determination of disturbances of the oxidative-antioxidative balance in patients with heart failure. The study group consisted of 37 patients, having the average age of 42.3 +/- 12.3 years, suffering from idiopathic or inflammatory heart failure. The patients have been qualified as degree II/III in accordance with NYHA scale. A statistically significant increase of anty-oxLDL level (254.28 +/- 80.79 vs 196.64 +/- 83.11 mU/ml; p<0.01) and malondialdehyde level (4.86 +/- 1.74 vs 3.71 +/- 1.19 micromol/l; p<0.05) has been demonstrated after 6-month observation. No statistically significant differences have been found for the activity of total superoxide dismutase (SOD) and its isoenzymes--(SOD-Mn) and (SOD-ZnCu). The results of the study indicate that no changes in SOD activity and increase in lipid peroxidation products level may lead to generation of oxidative stress may play an important role in the pathogenesis of heart failure.