Tonic chemoreflex activation contributes to increased sympathetic nerve activity in heart failure-related anemia

Sympathetic activation contributes to both the initiation and progression of heart failure. The role of anemia in determining sympathetic overactivity in chronic heart failure (CHF) patients is unknown. We tested the hypothesis that, in CHF patients, anemia could lead to increased sympathetic activity through tonic activation of excitatory chemoreceptor afferents. We conducted a double-blind, randomized, vehicle-controlled study to examine the effect of chemoreflex deactivation on muscle sympathetic nerve activity in CHF patients with and without anemia. We compared the effect of breathing 100% oxygen for 15 minutes in 18 stable CHF patients with anemia and 18 control CHF patients matched for age, sex, blood pressure, and body mass index. Baseline muscle sympathetic nerve activity was significantly elevated in CHF patients with anemia compared with patients with CHF alone (56.0+/-3.2 versus 45.5+/-3.1 bursts per minute; P<0.0237). Administration of 100% oxygen led to a significant decrease in muscle sympathetic nerve activity in CHF patients with anemia (from 56.0+/-3.4 to 50.9+/-3.2 bursts per minute; P<0.0019). In contrast, neither room air nor 100% oxygen changed muscle sympathetic nerve activity or hemodynamics in patients with CHF alone. We report for the first time direct evidence of increased sympathetic nerve traffic in patients with CHF-related anemia. Sympathetic hyperactivity in patients with CHF and anemia is partially chemoreflex mediated and could explain how anemia contributes to the progression of CHF and increases morbidity and mortality in these patients.