Exercise hyperpnoea: Unravelling layers of regulation

Abstract How ventilation () matches gas exchange () while maintaining isocapnia during exercise remains unresolved. We measured , , arterialized‐venous (PāCO 2 ) and hypercapnic ventilatory responsiveness (HCVR = ∆/∆) during four steady‐state exercise intensities below the respiratory compensation point (RCP) and used a mathematical model to characterize feedforward contributions to exercise hyperpnoea and test the hypothesis that CO 2 chemofeedback is inhibitory. Model assumptions were that the ventilatory response to exercise‐intensity changes (G SYS = ∆/∆) equals the sum of a feedforward exercise stimulus proportional to (G EX ) modified by the CO 2 chemoreflex (HCVR). Using experimental data G SYS was quantified as ∆/∆ between exercise steps and G EX equalled G SYS minus chemoreflex feedback (i.e. HCVRx∆PāCO 2 /∆). Twenty healthy young participants completed a maximal cycling test and three submaximal step‐incremental protocols of two 8 min stages below the estimated lactate threshold (θ LT ; MOD 1 and MOD 2 ) and two 12 min stages between θ LT and RCP (HVY 1 and HVY 2 ). During visits 2 and 3, three rebreathing tests performed at each intensity provided HCVR (average –end‐tidal slope). During visit 4, heated hand vein blood provided PāCO 2 at each intensity, and and were measured by metabolic cart. With higher steady‐state , one‐way repeated‐measures ANOVA showed that HCVR rose from 2.4 ± 0.9 at MOD 1 to 2.8 ± 0.8, 3.2 ± 0.8 and 3.6 ± 1.0 L · min −1 · mmHg −1 at MOD 2 , HVY 1 and HVY 2 , respectively; ∆PāCO 2 /∆ decreased ( P < 0.001) from 0.2 ± 4.3 at MOD 1 to −1.9 ± 5.0, −5.5 ± 4.5 and −8.0 ± 4.6 mmHg · L · min −1 ; and G EX increased ( P < 0.001) from 26.9 ± 15.1 at MOD 1 to 34.5 ± 20.3, 53.9 ± 19.1 and 73.4 ± 27.5 L · min −1 . Exercise hyperpnoea may reflect the balance of intensity‐dependent feedforward and inhibitory CO 2 chemofeedback drive. image Key points We aimed to quantify exercise intensity‐dependent changes in CO 2 chemoreflexes and interpret their role in exercise hyperpnoea. Ventilatory, gas exchange, arterialized‐venous (PāCO 2 ) and hypercapnic ventilatory responses (HCVR) were measured during successive work‐to‐work cycling exercise transitions from low‐to‐moderate to heavy‐intensity work rates. The measured HCVR at each intensity and ∆/∆ and ∆PāCO 2 /∆ from one work rate to the next were included in a mathematical model to characterize feedforward contributions to exercise hyperpnoea at four intensities. With increasing steady‐state , ∆/∆ and HCVR progressively increased, whereas ∆PāCO 2 /∆ progressively became more negative. Assuming ∆ is the sum of a feedforward gain plus linear CO 2 chemofeedback gain responding to changes in and from rest to exercise, respectively, we estimated that feedforward gain rises with increasing exercise intensities, attaining a drive that exceeds requirements for regulation at its resting level. Exercise hyperpnoea, therefore, requires a feedforward exercise stimulus constrained by inhibitory chemofeedback from rest to exercise to minimize hypocapnia .