Inflammation and its association with oxidative stress in dogs with heart failure.

BACKGROUND: Inflammation and oxidative stress can contribute to the development and progression of heart failure. This study aimed to investigate the association between inflammatory and oxidative stress markers in dogs with congestive heart failure (CHF). Associations between the disease severity marker N-terminal pro-B-type natriuretic peptide (NT-proBNP) and markers of inflammation and oxidative stress were also determined. RESULTS: Thirty-seven dogs with cardiovascular diseases (dilated cardiomyopathy, DCM (16 dogs), myxomatous mitral valve disease, MMVD (21 dogs)) and ten healthy dogs were included in this prospective study. The patients were further divided into groups with (26) and without CHF (11). We found a significantly higher serum concentration of C-reactive protein (P = 0.012), white blood cell (P = 0.001), neutrophil (P = 0.001) and monocyte counts (P = 0.001) in patients with CHF compared to control dogs. The concentration of tumor necrosis factor-alpha (TNF-α) was significantly higher in patients with CHF compared to patients without CHF (P = 0.030). No significant difference was found in most of the measured parameters between MMVD and DCM patients, except for glutathione peroxidase (GPX) and NT-proBNP. In patients with CHF, TNF-α correlated positively with malondialdehyde (P = 0.014, r = 0.474) and negatively with GPX (P = 0.026, r = - 0.453), and interleukin-6 correlated negatively with GPX (P = 0.046, r = - 0.412). NT-proBNP correlated positively with malondialdehyde (P = 0.011, r = 0.493). In patients without CHF none of the inflammatory and oxidative stress markers correlated significantly. Furthermore, in the group of all cardiac patients, GPX activity significantly negatively correlated with NT-proBNP (P = 0.050, r = - 0.339) and several markers of inflammation, including TNF-α (P = 0.010, r = - 0.436), interleukin-6 (P = 0.026, r = - 0.382), white blood cell (P = 0.032, r = - 0.369), neutrophil (P = 0.027, r = - 0.379) and monocyte counts (P = 0.024, r = - 0.386). CONCLUSION: Inflammatory and oxidative stress markers are linked in canine CHF patients, but not in patients without CHF. These results suggest complex cross communication between the two biological pathways in advanced stages of CHF.

Systemic inflammation in dogs with advanced-stage heart failure.

BACKGROUND: Although human studies have shown that inflammation plays a role in the development of congestive heart failure, scarce information exists on white blood cell count (WBC) and differential cell counts in various stages of heart failure in man and dogs. A few studies demonstrated increased concentrations of C-reactive protein (CRP), a major acute-phase protein, in cardiac diseases in dogs. Our research aimed to investigate whether CRP concentration, WBC and neutrophil count (NEUT), as markers of systemic inflammation, are elevated in canine cardiovascular patients. We also aimed to find out whether there is an association between CRP concentration and WBC and NEUT, as well as associations between these inflammatory markers and selected echocardiographic parameters. Sixty-two client-owned canine cardiac patients and 12 healthy dogs were included in the study. The patients were classified into International Small Animal Cardiac Health Council classes (ISACHC I-III). The serum CRP concentration was determined using a canine CRP test kit. WBC and NEUT were determined using an automated hematology analyzer. RESULTS: Significantly higher serum CRP concentration, WBC and NEUT were found in the decompensated stage of heart failure (ISACHC III) compared with healthy dogs and with patients in ISACHC group II and ISACHC group I. Serum CRP concentration significantly positively correlated with WBC (r = 0.65, P < 0.001) and NEUT (r = 0.58, P = 0.002) in the ISACHC III group, while no significant correlations were found in the ISACHC I and II groups. A significant negative correlation between serum CRP concentration and the left ventricular ejection fraction (r = - 0.49, P = 0.046) and a significant positive correlation between CRP and the E wave velocity of the mitral valve inflow (r = 0.52, P = 0.046) were found in the ISACHC III group. CONCLUSIONS: The CRP concentration, WBC and NEUT were significantly increased in advanced-stage heart failure patients in comparison with compensated patients and healthy dogs, which indicate the presence of systemic inflammation. However, normal CRP concentration and normal WBC and NEUT can also be present in heart failure.

Markers of oxidative stress in dogs with heart failure.

We tested the hypothesis that indirect measures of oxidative stress (vitamin E, glutathione peroxidase, and malondialdehyde) differ in dogs in heart failure resulting from either myxomatous mitral valve disease or dilated cardiomyopathy. Dogs were classified according to the International Small Animal Cardiac Health Council (ISACHC) classification. Additionally, the effect of cardiac therapy on oxidative stress parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in advanced stages of congestive heart failure was investigated. There were no significant differences in oxidative stress parameters between healthy dogs and the individual groups of cardiac patients. Significantly lower malondialdehyde (MDA) was observed in the ISACHC II group in comparison to ISACHC groups III and I. A significant positive correlation in treated patients was observed between NT-proBNP and MDA, NT-proBNP and vitamin E, as well as between MDA and vitamin E (and lipid-standardized vitamin E). No significant differences in any of the measured parameters were found between treated and non-treated cardiac patients. Our results suggest an association between MDA (the extent of lipid peroxidation) and NT-proBNP, vitamin E and NT-proBNP, as well as between MDA and vitamin E in treated canine patients. Plasma vitamin E concentration was maintained in all stages of cardiovascular disease in these canine patients.

Plasma coenzyme Q10 concentration, antioxidant status, and serum N-terminal pro-brain natriuretic peptide concentration in dogs with various cardiovascular diseases and the effect of cardiac treatment on measured variables.

OBJECTIVE To determine the plasma total antioxidant capacity, erythrocyte superoxide dismutase activity, whole blood glutathione peroxidase activity, and plasma coenzyme Q10 (CoQ10) concentration in dogs with various stages of cardiovascular diseases and in healthy dogs; assess the influence of cardiac treatment on the levels of antioxidant variables, plasma CoQ10 concentration, and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration, and determine any correlation between the disease severity (NT-proBNP concentration) and antioxidant variables or CoQ10 concentration. ANIMALS 43 dogs with various types and stages of cardiovascular diseases (congenital and acquired) and 29 healthy dogs. PROCEDURES Blood samples were collected from all dogs for spectrophotometric assessment of antioxidant variables. Plasma CoQ10 concentration was determined with a high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry method. Serum NT-proBNP concentration was measured with an ELISA. RESULTS Values for antioxidant variables did not differ among groups of dogs with cardiovascular diseases, regardless of disease stage or treatment. Plasma CoQ10 concentration was significantly increased in treated dogs with congestive heart failure (CHF), compared with untreated patients. However, plasma CoQ10 concentration did not differ among heart failure classes. A significant, negative correlation between serum NT-proBNP and plasma CoQ10 concentrations was identified in treated CHF-affected dogs, suggesting that low plasma CoQ10 concentration may be associated with increased severity of CHF. CONCLUSIONS AND CLINICAL RELEVANCE The antioxidant variables evaluated were not altered in dogs with CHF, regardless of cardiac disease stage or treatment. Further investigation into the possible effects of CoQ10 supplementation in dogs with advanced stages of CHF is warranted.