Carvedilol reduces exercise-induced hyperventilation: A benefit in normoxia and a problem with hypoxia

Aims: To evaluate whether carvedilol influences exercise hyperventilation and the ventilatory response to hypoxia in heart failure (HF). Methods and results: Fifteen HF patients participated to this double blind, randomised, placebo controlled, cross-over study. Patients were evaluated by quality of life questionnaire, echocardiography, pulmonary function and cardiopulmonary exercise tests (ramp and constant workload) both in normoxia (FiO₂ = 21%) and hypoxia (FiO₂ = 16%, equivalent to a simulated altitude of 2000 m). Carvedilol improved clinical condition and reduced left ventricle size, but had no effect on lung mechanics. In normoxia during exercise, ventilation was lower, V_CO2 unchanged and PaCO₂ (constant workload) or PetCO₂ (ramp) higher with carvedilol, exercise capacity was unchanged (peak workload 92 ± 22 and 90 ± 22 W for placebo and carvedilol, respectively). Abnormal V_E/V_CO2 slope was reduced by carvedilol. Hypoxia increased ventilation but less with carvedilol; exercise capacity decreased to 87 ± 21 W (placebo) and to 80 ± 11 W (carvedilol, p <0.01). With hypoxia, carvedilol decreased V_E/V_CO2 slope. At constant workload exercise with hypoxia, PaO₂ decreased to 69 ± 6 mm Hg (placebo) and to 64 ± 5 (carvedilol, p <0.01). Conclusion: Carvedilol reduced hyperventilation possibly by reducing peripheral chemoreflex sensitivity as suggested by PaCO₂ increase with normoxia and PaO₂ decrease with hypoxia without V_CO2 and V_D/V_T changes. Lessening hyperventilation is beneficial when breathing normally, but detrimental when hyperventilation is needed for exercise at high altitude.