1454 Patients with non-hypoxemic chronic obstructive pulmonary disease (COPD) have, in addition to high airway resistance and low exercise tolerance, high parasympathetic nervous system activity. Airway resistance, however, is reduced with high inspired fractions of helium (Heliox: 20% oxygen, 80% helium) through less turbulent airflow. PURPOSE: To test whether autonomic system function might be altered with Heliox breathing in COPD during exercise. This might occur through a mechanism linked to reduced dynamic hyperinflation and – possibly – smaller intrathoracic pressure. METHODS: Autonomic nervous system function was assessed at rest and during 20 Watt constant work rate exercise in eight non-hypoxemic COPD patients (72 ± 10 yrs; FEV1% predicted: 36.6 ± 9.1). This was achieved by analysis of R-R interval variability, derived from the ECG signal, using an autoregressive method. Subjects inspired air or Heliox from a balloon. The low-to-high frequency ratio (LF/HF) and the high-to-total frequency ratio (HF/TOT) were calculated as indices of sympathetic and parasympathetic autonomic tone, respectively (HF: 0.15 – 0.50 Hz; LF: 0.04 – 0.15 Hz). RESULTS: Heliox breathing slightly increased heart rate at rest, compared with air (73.6 ± 10.7 vs 68.9 ± 9.1 min−1, P < 0.05). During exercise both heart rate (93.8 ± 13.9 vs. 89.9 ± 11.6 min−1, P< 0.05) and breathing frequency (24.9 ± 3.6 vs. 23.4 ± 3.2 min−1) were higher on Heliox. While at rest there was no significant difference in autonomic tone indices between air and Heliox breathing, during exercise the HF/TOT ratio (parasympathetic index) was significantly lower with Heliox than with air (0.09 ± 0.08 vs. 0.17 ± 0.08, respectively, P < 0.05). Autonomic tone balance did not change from rest to exercise with air breathing; in contrast, the HF/TOT ratio was significantly reduced (0.09 ± 0.08 vs. 0.24 ± 0.11, P < 0.05) and the LF/HF ratio (sympathetic index) was significantly increased (1.56 ± 0.81 vs. 0.70 ± 0.28, P < 0.05) with Heliox breathing. CONCLUSIONS: During exercise Heliox breathing reduces PNS activity and shifts the autonomic tone balance towards sympathetic dominance in nonhypoxemic COPD patients. This may be conducive to improved airway function.