The role of group III/IV afferent feedback in the ventilatory, pressor and metabolic responses to exercise in normoxia and hypoxia.

Group III/IV muscle afferents play a prominent role in ensuring appropriate arterial oxygenation during exercise. Exercise in hypoxia poses a major cardiorespiratory challenge due to reduced inspired oxygen pressure (PIO2). Although humans adapt powerfully to hypoxia, the contribution of group III/IV afferents to ventilatory, pressor and metabolic responses to exercise in chronic hypoxia remains unknown. Fourteen healthy participants completed cycling trials with (placebo) and without (25 µg intrathecal fentanyl) intact group III/IV afferent feedback in three settings: (1) normoxia, PIO2 = 139 mmHg;  (2) acute hypoxia, PIO2 = 90 mmHg; and (3) chronic hypoxia, after 7-9 days of acclimatisation to 3800 m, PIO2 = 90 mmHg. Participants completed three 3-min stages at matched absolute intensities corresponding to 45%, 60% and 75% sea-level maximal aerobic power. Ventilation, pulmonary gas exchange, arterial blood gases and blood pressure were measured. Fentanyl suppressed exercise hyperpnoea similarly across environments (P < 0.001) but produced larger reductions in arterial oxygenation in hypoxia, lowering saturation by ∼3%-5% and content by ∼0.7-1.0 ml dL-1 (condition×PIO2, P ≤ 0.016). Fentanyl also blunted the exercise-induced increase in mean arterial pressure, with a greater blood pressure-lowering effect of -10 to 13 mmHg observed in hypoxia (condition×PIO2, P = 0.021). In contrast fentanyl increased circulating lactate and hydrogen ion concentration ([H+]) (P < 0.001), an effect accentuated during acute hypoxia (lactate: +1-2 mmol L- 1, [H+]: +2-5 nmol L- 1) but attenuated after acclimatisation (interactions, P ≤ 0.034). Thus group III/IV afferent feedback becomes more consequential in hypoxia, as small perturbations in ventilatory control and perfusion pressure have amplified consequences for oxygen transport. KEY POINTS: Group III/IV muscle afferent feedback contributes to normal exercise hyperpnoea and blood pressure regulation; whether its functional contribution is altered by acute and chronic hypoxia is unknown. In a double-blind, placebo-controlled cross-over design, 14 participants completed steady-state cycling with intact (placebo) or attenuated (intrathecal fentanyl) group III/IV afferent feedback in normoxia, acute hypoxia and after 7-9 days of acclimatisation at 3800 m. Intrathecal fentanyl suppressed exercise hyperpnoea similarly across environments but caused exaggerated arterial oxygen desaturation during hypoxic exercise, reflecting operation on the steep portion of the oxygen-haemoglobin dissociation curve. The blood pressure-lowering effect of intrathecal fentanyl was greater during hypoxic exercise; effects on metabolic strain were greatest in acute hypoxia and largely normalised after acclimatisation. These findings highlight the functional importance of group III/IV muscle afferent feedback during hypoxic exercise, where small perturbations in ventilatory and pressor control have amplified consequences for oxygen transport.

Duke Scholars

Author David Brett MacLeod Anesthesiology, Regional