On the significance of group III/IV muscle afferent feedback for the control of breathing and gas exchange efficiency during prolonged locomotor exercise
Authors: Iannetta Danilo , Weavil Joshua , Thurston Taylor , Georgescu Vincent , Fabio Laginestra , Inglis Erin , Robert Jenkinson , Curtis Michelle , Chang Jen , Amann Markus 
Published: May 2023

Introduction: By projecting to medullary respiratory center, group III/IV muscle afferents determine the ventilatory response during short (~3 min) bouts of locomotor exercise. However, their significance for the hyperpneic response, gas exchange efficiency, and arterial oxygenation during exercise of longer durations (>15min) remains unknown. Methods: On 2 separate days, 8 healthy subjects (22±3yrs, 4 f) performed two 20-min bicycling bouts at 30% (~50% V̇O2max) and 50% (~75% V̇O2max) of peak power (Wpeak) under a) control condition (intact leg muscle afferent feedback; CTRL), and b) lumbar intrathecal fentanyl (attenuated group III/IV leg muscle afferent feedback; FENT). Ventilation (V̇E) and gas exchange were continuously recorded, data averaged over the last min of each bout. Arterial blood samples (radial catheter) were used to determine O2 and CO2 partial pressures (PaO2 and PaCO2) and O2 saturation (HbO2). Alveolar O2 pressure (PAO2) was calculated, pulmonary gas exchange efficiency was evaluated using the alveolar-to-arterial O2 difference (A-aDO2) and the arterial-to-end-tidal PCO2 difference (PaCO2-PETCO2). Results: Fentanyl had no effect at rest. There was no difference in V̇O2, V̇CO2, and VT between CTRL and FENT. However, during FENT vs CTRL, V̇E (30 % Wpeak: 42±9 vs 46±8 L/min; 50 %Wpeak: 75±12 vs 71±12), f R (30 %: 25±3 vs 28±4b/min; 50%: 33±5 vs 35±5), V̇E/V̇O2 (30%: 25±3 vs 28±3; 50 %: 29±5 vs 32±4), V̇E/V̇CO2 (30 %: 31±4 vs 34±4; 50 %: 34±5 vs 37±5), PAO2 (30 %: 94±3 vs 97±5 mmHg; 50 %: 98±3 vs 100±4), PaO2 (30%: 84±5 vs 90±3 mmHg; 50%: 84±7 vs 88±4), HbO2 (30 %: 95±1 vs 96±1 %; 50 %: 95±2 vs 96±1 %), VD/VT (30 %: 0.18±0.04 vs 0.22±0.08; 50 %: 0.16±0.05 vs 0.21±0.07), and the PaCO2-PETCO2 difference (30 %: -2.6±1.6 vs -1.4±2.1 mmHg; 50 %: -2.8±2.4 vs -1.0±2.1) were lower ( P<0.05), while PaCO2 (30 %: 33±3 vs 31±3 mmHg; 50 %: 30±3 vs 29±3) and A-aDO2 (30 %: 9±3 vs 5±5 mmHg; 50 %: 14±5 vs 10±5) were greater ( P<0.05). Conclusions: In addition to regulating the initial ventilatory response, tonic feedback from group III/IV muscle afferents remains a key determinant of the pulmonary response during prolonged locomotor exercise. The relative importance of these sensory neurons for optimizing exercise hyperpnea is emphasized by the fact that the pulmonary response to bicycling with attenuated sensory feedback remains inadequate despite concomitant increases in potent ventilatory stimuli (↑PaCO2, ↓PaO2). We conclude that group III/IV muscle afferent feedback is critical for matching the pulmonary response to the metabolic cost of locomotion and for perpetually optimizing gas exchange efficiency and arterial oxygenation during longer exercise. National Heart, Lung, and Blood Institute (HL-116579), U.S. Veterans Affairs Rehabilitation Research and Development (E3343-R) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.