The ability of neutrophils to generate superoxide anions is increased in chronic heart failure and correlates with NYHA status

Increased oxidative stress has been implicated in the genesis and maintenance of chronic heart failure (CHF) though the primary source of oxygen free radicals involved in this process remains unclear. Superoxide anfon (O2-.) generation by neutrophils primed by tumour necrosis factor-α and modulated by angiotensin II may be one important potential mechanism. To test this hypothesis we measured the O2-. generating ability of activated neutrophils taken from CHF patients. Methods: We studied 12 patients with NYHA class I/IV symptoms of CHF, LV ejection fractions <35% on optimal medical therapy and 12 matched healthy controls. Morning venous blood samples were taken in heparinised tubes and analysed immediately. Neutrophils were separated from venous blood, employing a standard methodology, and O2-. generation measured at baseline and after in vitro activation with N-formyl-met-leu-phe employing lucigenin-based chemiluminescence. Results: The two groups were well matched for age and sex. Neutrophils taken from CHF patients produced significantly greater levels of O2-. when activated [(mean ± SD) CHF = 52.4 ± 29.6mV vs. C = 19.6 ± 8.1mV, p<0.005]. A correlation was shown between NYHA status and neutrophil O2-. generation in the CHF group (r = 0.74). Conclusion: Our findings support previous work suggesting increased oxidative stress in CHF and also implicate neutrophils as the main source of O2-. in this process though the exact underlying pathophysiological mechanisms need to be studied further.