Mechanism of augmented exercise hyperpnea in chronic heart failure and dead space loading

Patients with chronic heart failure (CHF) suffer increased alveolar _{V D}/_{V T} (dead-space-to-tidal-volume ratio), yet they demonstrate augmented pulmonary ventilation such that arterial PCO2 (PaCO2) remains remarkably normal from rest to moderate exercise. This paradoxical effect suggests that the control law governing exercise hyperpnea is not merely determined by metabolic CO₂ production (V̇CO2) per se but is responsive to an apparent (real-feel) metabolic CO₂ load (V̇CO2o) that also incorporates the adverse effect of physiological _{V D}/_{V T} on pulmonary CO₂ elimination. By contrast, healthy individuals subjected to dead space loading also experience augmented ventilation at rest and during exercise as with increased alveolar _{V D}/_{V T} in CHF, but the resultant response is hypercapnic instead of eucapnic, as with CO₂ breathing. The ventilatory effects of dead space loading are therefore similar to those of increased alveolar _{V D}/_{V T} and CO₂ breathing combined. These observations are consistent with the hypothesis that the increased series _{V D}/_{V T} in dead space loading adds to V̇CO2o as with increased alveolar _{V D}/_{V T} in CHF, but this is through rebreathing of CO₂ in dead space gas thus creating a virtual (illusory) airway CO₂ load within each inspiration, as opposed to a true airway CO₂ load during CO₂ breathing that clogs the mechanism for CO₂ elimination through pulmonary ventilation. Thus, the chemosensing mechanism at the respiratory controller may be responsive to putative drive signals mediated by within-breath PaCO2 oscillations independent of breath-to-breath fluctuations of the mean PaCO2 level. Skeletal muscle afferents feedback, while important for early-phase exercise cardioventilatory dynamics, appears inconsequential for late-phase exercise hyperpnea. © 2012 Elsevier B.V.