8-hydroxy-2--deoxyguanosine and Cardiac-Output--Low

Oxidative stress has been implicated in the pathogenesis of chronic heart failure. The present study investigated whether the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were elevated in the serum and myocardium of patients with dilated cardiomyopathy (DCM), and furthermore whether carvedilol, a vasodilating beta-blocker with antioxidant activity, could reduce the levels.. Serum levels of 8-OHdG were measured by enzyme immunoassay in 56 patients with DCM and in 20 control subjects. DCM patients had significantly elevated serum levels of 8-OHdG compared with control subjects. Endomyocardial biopsy samples obtained from 12 DCM patients and 5 control subjects with normal cardiac function were studied immunohistochemically for the expression of 8-OHdG. Positive 8-OHdG staining was found in the nuclei of cardiomyocytes from DCM patients but not in those from control subjects. After treatment with carvedilol, the serum levels of 8-OHdG in DCM patients significantly decreased by 19%, together with amelioration of heart failure.. Levels of 8-OHdG are elevated in the serum and myocardium of patients with heart failure. Treatment with carvedilol might be effective for decreasing the oxidative DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adrenergic beta-Antagonists; Adult; Aged; Biomarkers; Carbazoles; Cardiac Output, Low; Carvedilol; Deoxyguanosine; DNA Damage; Female; Heart; Heart Rate; Humans; Immunohistochemistry; Male; Middle Aged; Myocardium; Oxidative Stress; Propanolamines

Although oxidative stress mediated by reactive oxygen species plays an important role in the pathogenesis of heart failure (HF), good clinical markers for reactive oxygen species in patients with HF have not been established. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is formed from deoxyguanosine in DNA by hydroxyl free radicals and might serve as a sensitive biomarker of intracellular oxidative stress in vivo. Thioredoxin (TRX) is known to be induced in cells as a radical scavenger against oxidative stress. The aim of this study is to evaluate the clinical significance of the serum 8-OHdG and TRX of patients with chronic HF with idiopathic dilated cardiomyopathy (DCM).. We estimated serum 8-OHdG and TRX levels using enzyme-linked immunosorbent assay in 32 patients with DCM and investigated the impact of these markers to the clinical characteristics of these patients. Serum levels of 8-OHdG, but not TRX were significantly correlated with New York Heart Association functional class, left atrial diameters, left ventricular end-diastolic diameters, left ventricular end-systolic diameters, and plasma levels of brain natriuretic peptide.. These data suggest oxidative DNA damage is increased in patients with DCM according to the severity of HF. Serum levels of 8-OHdG may represent clinically useful markers of left ventricular remodeling.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Cardiac Output, Low; Cardiomyopathy, Dilated; Chronic Disease; Deoxyguanosine; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxidative Stress; Severity of Illness Index; Thioredoxins