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.

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 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 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.

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 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.

Oxidative Stress Markers and Modified Model for End-Stage Liver Disease Are Associated with Outcomes in Patients with Advanced Heart Failure Receiving Bridged Therapy with Continuous-Flow Left Ventricular Assist Devices.

Left ventricular assist device (LVAD) is well established as an alternative treatment for end-stage heart failure (HF) patients. The aim of the study was to determine the prognostic value of oxidative stress markers and the modified Model for End-Stage Liver Disease (modMELD) in patients receiving bridged therapy with continuous-flow LVAD. We prospectively analyzed 36 end-stage HF patients who received LVAD therapy between 2015 and 2018. The total antioxidant capacity (TAC) and total oxidant status (TOS) were measured by the methods described by Erel. The oxidative stress index (OSI) was defined as the ratio of the TOS to TAC levels. The modMELD scores were calculated based on the serum bilirubin, creatinine, and albumin levels. The patients' median age was 58 (50-63.0) years. During the 1.5-years follow-up, a major adverse cardiac event-MACE (death, stroke, or pump thrombosis) was observed in 17 patients (47.2%). The area under the receiver operating characteristics curves (AUCs) indicated a good prognostic power of TAC (AUC 0.7183 (0.5417-0.8948)), TOS (AUC 0.9149 (0.8205-0.9298)), OSI (AUC 0.9628 (0.9030-0.9821)), and modMELD (AUC 0.87 (0.7494-0.9905)) to predict a MACE. Oxidative stress markers serum concentrations, as well as the modMELD score, allow the identification of patients with a risk of MACE.

Fetuin-A and sodium concentrations are independently associated with all-cause mortality in patients awaiting heart transplantation.

INTRODUCTION: End­stage heart failure (HF) is a clinical condition with complex pathophysiology and poor prognosis. OBJECTIVES: This study aimed to identify factors associated with mortality during a 1.5­year follow­up in patients with end­stage HF. PATIENTS AND METHODS: We prospectively analyzed 72 patients hospitalized with end­stage HF. During right heart catheterization, 10 ml of coronary sinus (CS) blood was collected. The endpoint was all­cause mortality during a 1.5­yearfollow­up. We used a multivariable logistic regression model to find  factors associated with all­cause mortality. We created 2 separate models for CS fetuin and peripheral blood (PB) fetuin. RESULTS: The median (interquartile range) age of the patients was 58 (50-61.50) years. During the follow­up, 43.1% of the patients died. Lower levels of fetuin­A in the CS (OR, 1.103; 95% CI, 1.045-1.164; P <0.001, per 10-unit decrease in fetuin concentration) and PB samples (OR, 1.098; 95% CI, 1.046-1.153; P <0.001, per 10-unit decrease in fetuin concentration), along with lower plasma sodium levels (OR, 1.563; 95% CI, 1.134-2.156; P = 0.006 in the first model and OR, 1.639; 95% CI, 1.209-2.227; P = 0.002 in the second model; per 1-unit decrease in sodium concentration) were independently associated with death during the follow­up period. The area under the receiver operating characteristics curve (AUC) indicated a good prognostic power of CS and PB fetuin­A levels (AUC, 0.917 and AUC, 0.850, respectively) and an acceptable prognostic power of sodium concentration (AUC, 0.788). CONCLUSIONS: Lower levels of CS and PB fetuin­A, as well as lower sodium levels, are associated with an increased risk of death in patients with end­stage 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.

Electromagnetic Fields Modify Redox Balance in the Rat Gastrointestinal Tract.

Objective: The aim of the study was to assess the influence of electromagnetic fields with divergent physical properties on the prooxidative and antioxidative balances in homogenates of the tongue, salivary glands, esophagus, stomach, and small and large intestines of rats. Material and Methods: Forty rats were randomly divided into four equal groups, namely, a control group, a group exposed to low-frequency electromagnetic fields (LF-EMFs; frequency: 50 Hz; intensity: 10 kV/m; magnetic induction: 4.3 pT), a group exposed to radiofrequency electromagnetic fields (RF-EMFs) emitted by mobile phones (frequency: 900 MHz), and a group exposed simultaneously to LF-EMFs and RF-EMFs emitted by mobile phones. After 28 consecutive days of the experiment, the following pro- and antioxidative markers were assessed in the gastrointestinal tract homogenates: superoxide dismutase (SOD) and its two isoenzymes (Mn-SOD, Cu,Zn-SOD) catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), total antioxidative capacity (TAC), total oxidative status (TOS), and malondialdehyde (MDA). Results: In rats exposed to LF-EMFs, higher concentrations of the markers of prooxidant processes, MDA or TOS, were observed in the salivary glands, esophagus, and small intestine homogenates in comparison with the control group. Additionally, in the group of rats opposite to the control, antioxidant activity was observed. The main differences included a higher activity of Cu,Zn-SOD in homogenates of the tongue, salivary glands, and esophagus as well as decreased activity of CAT in homogenates of the tongue, esophagus, and small intestine. In animals exposed to RF-EMFs, the concentration of TOS was higher in the large intestine than in control rats. The main difference of antioxidant activity was presented by decreased Cu,Zn-SOD in homogenates of the salivary glands, stomach, small and large intestine as well as CAT in homogenates of the tongue, esophagus, stomach, and small and large intestine. Moreover, in rats exposed simultaneously to LF-EMFs and RF-EMFs, a lower concentration of TOS was observed. Antioxidant activity was presented by a decreased activity of CAT in homogenates of the tongue, esophagus, stomach, and small and large intestine in comparison to the control group. Conclusion: Among those applied in the study, electromagnetic fields of a low-frequency caused the most significant disturbances of oxidative stress in the rat gastrointestinal tract.

Serum Sulfhydryl Groups, Malondialdehyde, Uric Acid, and Bilirubin as Predictors of Adverse Outcome in Heart Failure Patients due to Ischemic or Nonischemic Cardiomyopathy.

Oxidative stress plays a significant role in the pathogenesis of heart failure (HF). The aim of the study was to investigate the prognostic value of oxidation-reduction (redox) markers in patients with HF due to ischemic and nonischemic cardiomyopathy. The study included 707 patients of HF allocated into two groups depending on ethology: ischemic cardiomyopathy (ICM) (n = 435) and nonischemic cardiomyopathy (nICM) (n = 272), who were followed up for one year. The endpoint occurrence (mortality or heart transplantation) in a 1-year follow-up was similar in the ICM and nICM group. The predictive value of endpoint occurrence of oxidative stress biomarkers such as the serum protein sulfhydryl groups (PSH), malondialdehyde (MDA), uric acid (UA), bilirubin, and MDA/PSH ratio and other clinical and laboratory data were assessed in both groups (ICM and nICM) separately using univariate and multivariate Cox regression analyses. In multivariate analysis, the higher concentrations of UA (p = 0.015, HR = 1.024, 95% CI (1.005-1.044)) and MDA (p = 0.004, HR = 2.202, 95% CI (1.296-3.741)) were significantly associated with adverse prognosis in patients with ICM. Contrastingly, in patients with nICM, we observed that higher bilirubin concentration (p = 0.026, HR = 1.034, 95% CI (1.004-1.064)) and MDA/PSH ratio (p = 0.034, HR = 3.360, 95% CI (1.096-10.302)) were significantly associated with increased risk of death or HT. The results showed the association of different oxidative biomarkers on the unfavorable course of heart failure depending on etiology.

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.

Factors Associated with Ineffectiveness of Sildenafil Treatment in Patients with End-Stage Heart Failure and Elevated Pulmonary Vascular Resistance.

INTRODUCTION: Elevated pulmonary vascular resistance (PVR) unresponsive to vasodilator treatment is a marker of heart failure (HF) severity, and an important predictor of poor results of heart transplantation (HT). OBJECTIVE: We sought to analyze factors associated with ineffectiveness of sildenafil treatment in end-stage HF patients with elevated PVR with particular emphasis placed on tenascin-C (TNC) serum concentrations. PATIENTS AND METHODS: The study is an analysis of 132 end-stage HF patients referred for HT evaluation in the Cardiology Department between 2015 and 2018. TNC was measured by sandwich enzyme-linked immunosorbent assay (Human TNC, SunRedBio Technology, Shanghai, China). The endpoint was PVR > 3 Wood units after the six-month sildenafil therapy. RESULTS: The median age was 58 years, and 90.2% were men. PVR >3 Wood units after 6 months of sildenafil treatment were found in 36.6% patients. The multivariable logistic regression analysis confirmed that TNC (OR = 1.004 (1.002-1.006), p = 0.0003), fibrinogen (OR= 1.019 (1.005-1.033), p = 0.085), creatinine (OR =1.025 (1.004-1.047), p = 0.0223) and right ventricular end-diastolic dimension (RVEDd) (OR = 1.279 (1.074-1.525), p = 0.0059) were independently associated with resistance to sildenafil treatment. Area under the ROC curves indicated an acceptable power of TNC (0.9680 (0.9444-0.9916)), fibrinogen (0.8187 (0.7456-0.8917)) and RVEDd (0.7577 (0.6723-0.8431)), as well as poor strength of creatinine (0.6025 (0.4981-0.7070)) for ineffectiveness of sildenafil treatment. CONCLUSIONS: Higher concentrations of TNC, fibrinogen and creatinine, as well as a larger RVEDd are independently associated with the ineffectiveness of sildenafil treatment. TNC has the strongest predictive power, sensitivity and specificity for evaluation of resistance to sildenafil treatment.

Investigation of the Role of Oxidative Stress and Factors Associated with Cardiac Allograft Vasculopathy in Patients after Heart Transplantation.

Oxidative stress is defined as an imbalance between the production of free radicals and their elimination by the antioxidant defense system. However, the role of oxidative stress in cardiac allograft vasculopathy (CAV) has not been fully understood. Therefore, this study is aimed at determining the role of oxidative-antioxidative balance disturbances in patients after HT. Furthermore, we sought to analyze factors associated with the presence of CAV, with particular emphasis placed on oxidative stress markers. The study analyzed data of 194 consecutive patients after HT who underwent routine visits in the Transplantation Clinic between 2015 and 2016. Total oxidant status (TOS) and total antioxidant capacity (TAC) were measured by the method described by Erel. The oxidative stress index (OSI) was defined as the ratio of the TOS to TAC levels. Patients' mean age was 55.4 ± 15.0 years, and 73.4% were men. The frequency of CAV was 50%. The area under the receiver operating characteristic curves indicated a good discriminatory power of TAC and TOS (0.8940 (0.8515-0.9365); 0.8620 (0.8126-0.9114), respectively) as well as excellent discriminatory power of OSI (0.9530 (0.9279-0.9781)) for CAV detection. Multivariate analysis of the Cox proportional hazard model confirmed that OSI (hazard ratio (HR) = 1.294 (1.204-1.391), p < 0.0001), age (HR = 1.023 (1.006-1.041), p = 0.0091), and high-sensitivity C-reactive protein (HR = 1.049 (1.016-1.083), p = 0.0151) were independently associated with CAV presence. In conclusion, TAC and TOS had a good discriminatory power and OSI had excellent strength for detecting CAV. The independent factors of CAV were higher OSI and CRP levels, as well as older recipient age.

Basic Studies on the Oxidative Stress Markers in Two Types of Horse Breed: Semi-isolated Population of Huculs Is Different from Commercially Used Arabian Horses.

Hucul and Arabian horses differ in the physiological constitution and exposition to environmental conditions. Oxidative stress plays a pathogenic role in many diseases and enables further injuries. The objective of this study was to compare the levels of enzymatic and nonenzymatic oxidative stress markers in Hucul horses living in seminatural conditions and in commercially handled Arabian horses. We tested the serum samples for total superoxide dismutase (total SOD), Cu-Zn-superoxide dismutase (CuZnSOD), and Mn-dependent superoxide dismutase (MnSOD) activity; for lipofuscin (LPS), ceruloplasmin (CER) and malondialdehyde (MDA) concentration; and for total antioxidant capacity (TAC) and total oxidant status (TOS). Total SOD (p < 0.001), MnSOD (p < 0.001), and CuZnSOD (p < 0.001) activities were significantly higher whereas LPS (p < 0.05), TAC (p < 0.001), TOS (p < 0.001), and MDA (p < 0.001) concentrations were significantly lower in the serum samples collected from Huculs vs. Arabian horses, regardless of the gender. Gender, regardless of the breed, had no significant impact on the antioxidants' activity and concentration. Total SOD and MnSOD activities were significantly higher in Hucul's mares when compared to Hucul's stallions. Concentrations of TAC and TOS were significantly lower in Arabian stallions than in Arabian mares. Commercially handled horses expressed a higher level of oxidative stress markers in comparison to breeds living in seminatural conditions. We conclude that antioxidants are important biomarkers of animal health, whether they are under maintenance care or performing physical exercise.

Factors associated with elevated pulmonary vascular resistance in ambulatory patients with end-stage heart failure accepted for heart transplant.

INTRODUCTION: Pulmonary hypertension (PH) is a common complication of heart failure (HF) that results in worse prognosis and heart complications following heart transplantation. To better define and understand left­sided PH, it is necessary to integrate the clinical context, noninvasive assessment, and invasive hemodynamic variables. OBJECTIVE: The aim of the study was to search for noninvasive factors related to the presence of PH with elevated pulmonary vascular resistance (PVR) in patients with advanced HF. PATIENTS AND METHODS: The study is a retrospective analysis of 282 patients with end­stage HF accepted for transplantation in the cardiology department between 2016 and 2018. A panel of laboratory tests, echocardiography, ergospirometry, and right heart catheterization were performed in all included patients. The Model for End­Stage Liver Disease Excluding INR (MELD­XI) and the Heart Failure Survival Score (HFSS) were calculated according to the appropriate formulas. RESULTS: The median age was 57 (51-60) years and 87.6% of patients were men. Pulmonary hypertension with elevated PVR was found in 30.1% of patients. The multivariable logistic regression analysis confirmed that lower HFSS (OR, 0.59; 95% CI, 0.383-0.908; P = 0.016), and higher MELD­XI scores (OR, 1.13; 95% CI, 1.024-1.24; P = 0.014), as well as higher alkaline phosphatase levels (OR, 1.02; 95% CI, 1.007-1.024; P <0.001) were independent factors associated with increased PVR. CONCLUSIONS: To the best of our knowledge, this is the first study to demonstrate that high MELD­XI and low HFFS scores, as well as high alkaline phosphatase serum concentrations were independently associated with increased PVR in patients with advanced HF referred for transplantation.

Effects of Advanced Age, Pituitary Pars Intermedia Dysfunction and Insulin Dysregulation on Serum Antioxidant Markers in Horses.

The study aims to assess the impact of age, pituitary pars intermedia dysfunction (PPID) and insulin dysregulation (ID) in horses on selected oxidative stress markers. The study includes 32 horses, divided into three groups: "young" adult group (aged 8-16 years old) "geriatric" group (aged 18-24 years old) and the "PPID" group (aged 15-31 years old). The PPID group was further divided into two subgroups: PPID ID+ and PPID ID- based on presence or absence of ID. We measured serum antioxidant stress markers in all horses: total oxidant status (TOS), total antioxidant capacity (TAC), ceruloplasmin (CER), lipofuscin (LPS), malondialdehyde (MDA) and thiols concentrations (containing sulfhydryl group -SH) as well as enzymatic systems: total superoxide dismutase (SOD), cytoplasmic SOD (CuZnSOD), mitochondrial SOD activity (MnSOD). Total serum thiols were significantly lower in the geriatric group and in the PPID group compared to the young group. The MnSOD concentration was higher in the PPID ID+ group compared to the PPID ID-. LPS and MDA concentrations were lower in the PPID ID+ group compared to the PPID ID- group. In the selected study groups of horses, older age, the presence of PPID and ID in the case of PPID had no effect on the studied oxidative stress markers.

The Oxidative Stress Markers in the Erythrocytes and Heart Muscle of Obese Rats: Relate to a High-Fat Diet but Not to DJOS Bariatric Surgery.

Obesity and high-fat diet (HF) are prevalent causes of oxidative stress (OS). Duodenal-jejunal omega switch (DJOS) is a bariatric procedure used for body mass reduction, extensively tested in animal models. We studied the long-term impact of bariatric surgery and an HF diet on the oxidative stress markers in erythrocytes and heart muscles of rats. We analyzed superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) activity and malondialdehyde (MDA) concentration in DJOS or SHAM (control) operated rats fed with different dietary protocols (control diet (CD) and high-fat diet (HF)), before and after the surgery (CD/CD, HF/HF, CD/HF, and HF/CD). We observed higher erythrocytes CAT, GST and GPx activity in DJOS-operated (vs. SHAM) rats fed with an HF/HF diet. For DJOS-operated rats, erythrocytes CAT and GPx activity and MDA concentration were significantly lower in CD/CD group. We observed increased heart muscle GR activity in SHAM-operated rats (vs. DJOS bariatric surgery) fed with an HF/HF diet. Change from HF to CD diet increased heart muscle GPx activity after DJOS bariatric surgery. Heart muscle SOD activity was lower in HF/HF and CD/CD groups after DJOS bariatric surgery (vs. SHAM). DJOS surgery significantly reduced heart muscle MDA concentration in HF/HF and HF/CD groups (vs. SHAM). We conclude that the selected dietary patterns had a stronger impact on oxidative stress markers in erythrocytes and heart muscle than DJOS bariatric surgery.

Ceruloplasmin, NT-proBNP, and Clinical Data as Risk Factors of Death or Heart Transplantation in a 1-Year Follow-Up of Heart Failure Patients.

We investigated whether the additional determination of ceruloplasmin (Cp) levels could improve the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) patients in a 1-year follow-up. Cp and NT-proBNP levels and clinical and laboratory parameters were assessed simultaneously at baseline in 741 HF patients considered as possible heart transplant recipients. The primary endpoint (EP) was a composite of all-cause death (non-transplant patients) or heart transplantation during one year of follow-up. Using a cut-off value of 35.9 mg/dL for Cp and 3155 pg/mL for NT-proBNP (top interquartile range), a univariate Cox regression analysis showed that Cp (hazard ratio (HR) = 2.086; 95% confidence interval (95% CI, 1.462-2.975)), NT-proBNP (HR = 3.221; 95% CI (2.277-4.556)), and the top quartile of both Cp and NT-proBNP (HR = 4.253; 95% CI (2.795-6.471)) were all risk factors of the primary EP. The prognostic value of these biomarkers was demonstrated in a multivariate Cox regression model using the top Cp and NT-proBNP concentration quartiles combined (HR = 2.120; 95% CI (1.233-3.646)). Lower left ventricular ejection fraction, VO2 max, lack of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, and nonimplantation of an implantable cardioverter-defibrillator were also independent risk factors of a poor outcome. The combined evaluation of Cp and NT-proBNP had advantages over separate NT-proBNP and Cp assessment in selecting a group with a high 1-year risk. Thus multi-biomarker assessment can improve risk stratification in HF patients.