Relationship between tumor necrosis factor-alpha production and oxidative stress in the failing hearts of patients with dilated cardiomyopathy

Objectives This study evaluated oxidative stress in the failing ventricle i n patients with dilated cardiomyopathy (DCM). Background Oxidative stress appears to increase in the failing myocardium a nd may contribute to ventricular dysfunction in patients with DCM. Tumor ne crosis factor-alpha (TNF-alpha), which is expressed in the failing heart, m ay stimulate oxidative stress. Methods We measured plasma oxidized low density lipoprotein (oxLDL) by sand wich enzyme-linked immunosorbent assay using specific antibodies against ox LDL in the aortic root (AO) and the coronary sinus (CS) in control subjects (n = 8) and in 22 patients with DCM and mild congestive heart failure. We also measured the plasma levels of TNF-alpha and angiotensin Results There was no difference in oxLDL between the AO and CS in control s ubjects. In contrast, plasma oxLDL was significantly higher in the CS than the AO in patients with DCM, suggesting that the transcardiac gradient of o xLDL reflects oxidative stress in the failing heart in these patients. Plas ma TNF-alpha levels were significantly higher in the CS than the AO with a significant positive correlation of the transcardiac gradient of TNF-alpha and the transcardiac gradient of oxLDL. Moreover, a significant negative co rrelation existed between the transcardiac gradient of oxLDL and left ventr icular ejection fraction. The transcardiac gradient of plasma oxLDL was sig nificantly lower in 6 patients who received carvedilol than in 16 patients who did not receive carvedilol. Conclusions These findings indicate that the transcardiac gradient of oxLDL may be a marker of oxidative stress in the heart and that left ventricular dysfunction may be partly due to the oxidative stress in patients with DCM . In addition, TNF-alpha may stimulate oxidative stress in the failing hear t in patients with DCM. (J Am Coll Cardiol 2001;37:2086-92) (C) 2001 by the American College of Cardiology.