Background: Previous work suggests that mild chronic obstructive pulmonary disease (COPD) patients have greater lung dysfunction than previously appreciated from spirometry alone. There is evidence of pulmonary microvascular dysfunction in mild COPD, which may reduce diffusing capacity (DLCO) and increase ventilatory inefficiency during exercise. The purpose of this study was to determine if DLCO, pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) are diminished during exercise in mild COPD, and whether this is related to ventilatory inefficiency and dyspnea. Methods: Seventeen mild COPD patients (FEV 1 /FVC: 64 ± 4%, FEV 1 = 94 ± 11% pred) and 17 age-and sexmatched controls were recruited. Ten moderate COPD patients were also tested for comparison (FEV 1 = 66 ± 7% pred). DLCO, Vc, and Dm were determined using the multiple-fraction of inspired oxygen (F I O 2) DLCO method at baseline and during steady-state cycle exercise at 40W, 50%, and 80% of VO 2peak. Using expired gas data, ventilatory inefficiency was assessed by V /VCO E 2. Results: Compared to controls, mild COPD had lower DLCO at baseline and during exercise secondary to diminished Vc (P < 0.05). No difference in Dm was observed between controls and mild COPD at rest or during exercise. Patients with high V /VCO E 2 (i.e. ≥34) had lower Vc and greater dyspnea ratings compared to control at 40W. Moderate COPD patients were unable to increase Vc with increasing exercise intensity, suggesting further pulmonary vascular impairment with increased obstruction severity. Conclusion: Despite relatively minor airflow obstruction, mild COPD patients exhibit a diminished DLCO and capillary blood volume response to exercise, which appears to contribute to ventilatory inefficiency and greater dyspnea.

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New Findings What is the Central question?Does dopamine, a pulmonary vascular vasodilator, contribute to the regulation of pulmonary diffusing capacity and capillary blood volume responses to exercise and exercise tolerance? What are the main findings and their importance?Dopamine appears not to be important for regulating pulmonary diffusing capacity or pulmonary capillary blood volume during exercise in healthy participants. Dopamine blockade trials demonstrated that endogenous dopamine is important for maintaining exercise tolerance; however, exogenous dopamine does not improve exercise tolerance. Abstract Pulmonary capillary blood volume (Vc) and diffusing membrane capacity (Dm) expansion are important contributors to the increased pulmonary diffusing capacity (DLCO) observed during upright exercise. Dopamine is a pulmonary vascular vasodilator, and recent studies suggest that it may play a role in Vc regulation through changes in pulmonary vascular tone. The purpose of this study was to examine the effect of exogenous dopamine and dopamine receptor‐2 (D2‐receptor) blockade on DLCO, Vc and Dm at baseline and during cycle exercise, as well as time‐to‐exhaustion at 85% of V̇O2 peak . We hypothesized that dopamine would increase DLCO, Vc, Dm and time‐to‐exhaustion, while D2‐receptor blockade would have the opposite effect. We recruited 14 young, healthy, recreationally active subjects (V̇O2 peak 45.8 ± 6.6 ml kg−1 min−1). DLCO, Vc and Dm were determined at baseline and during exercise at 60% and 85% of V̇O2 peak under the following randomly assigned and double blinded conditions: (1) intravenous saline and placebo pill, (2) intravenous dopamine (2 µg kg−1 min−1) and placebo pill, and (3) intravenous saline and D2‐receptor antagonist (20 mg oral metoclopramide). Exogenous dopamine and dopamine blockade had no effect on DLCO, Vc and Dm responses at baseline or during exercise. Dopamine blockade reduced time‐to‐exhaustion by 47% (P = 0.04), but intravenous dopamine did not improve time‐to‐exhaustion. While dopamine modulation did not affect DLCO, Vc or Dm, the reduction in time‐to‐exhaustion with D2‐receptor blockade suggests that endogenous dopamine is important for exercise tolerance.

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