Regulation of Ventilation and Perceived Effort of Breathing by Locomotor Muscle Metaboreceptor Afferents in Patients with Chronic Obstructive Pulmonary Disease
Authors: Aranda Liliane Cunha , Ribeiro Indyanara Cristina , Degani-Costa Luiza H. , Freitas Tiago Obeid , Vianna Lauro C. , Nery Luiz E. , Silva Bruno M. 
Published: April 2020

Exercise intolerance in chronic obstructive pulmonary disease (COPD) is greater for lower limb locomotor exercise as compared to upper limb exercise, presumably due to greater ventilatory constraint and sense of breathing effort (the main component of dyspnea sensation) in the former. Muscle afferent signaling has been proposed to be involved on dysfunctional ventilatory and perceptual responses to exercise in COPD. However, ventilatory responses to muscle metaboreflex activation in locomotor muscles remain uninvestigated. Moreover, regardless of exercise mode, the effect of muscle metaboreflex activation on perceived effort of breathing has never been explored. Therefore, we investigated the effect of locomotor muscle metaboreflex activation on ventilation and perceived effort of breathing in COPD. Nine patients with moderate‐to‐severe COPD and nine age‐ and sex‐matched controls (CON) performed constant work rate cycle ergometry using both lower limbs. Workload was set at 75% of maximal for 4 min. Then subjects recovered at rest for 2 min either with or without unilateral lower limb circulatory occlusion. After a 30‐min interval, subjects were crossed over to the other experimental trial. On another visit, patients were submitted to the cold pressor test (CPT; hand immersion on iced water).The CPT was used to provoke a stress response independently from muscle afferents activation. In contrast to free flow recovery, recovery with circulatory occlusion increased systolic and diastolic arterial pressures, increased pulmonary ventilation, increased respiratory frequency and decreased expiratory time similarly in COPD and CON. Circulatory occlusion did not change tidal volume in both groups. Of note, circulatory occlusion decreased inspiratory time (mean±SD; COPD: occlusion = 0.90±0.27 vs free flow = 1.00±0.20 units; P < 0.01; CON: occlusion = 1.24±0.37 vs free flow = 1.22±0.29 units; P = 0.66) and increased inspiratory flow (COPD: occlusion = 1.09 ± 0.25 vs free flow = 0.90 ± 0.10 L/s; P < 0.01; CON: occlusion = 0.95 ± 0.27 vs free flow = 0.92 ± 0.23 L/s; P = 0.61), a surrogate of the inspiratory drive, only in COPD. On the other hand, circulatory occlusion increased perceived effort of breathing only in CON (COPD: occlusion = 1.4±0.9 vs free flow = 1.1±0.9 units; P = 0.53; CON: occlusion = 4.3±2.3 vs free flow = 1.9±1.1 units; P < 0.001). CPT increased arterial pressure, but did not change pulmonary ventilation, respiratory pattern and perceived effort of breathing in COPD. In conclusion, locomotor muscle metaboreflex activation stimulated pulmonary ventilation and inspiratory drive without affecting perceived effort of breathing in patients with COPD. Such responses were specific to the muscle metaboreflex activation and suggest that the muscle metaboreflex per se is not linked with the origin of COPD exertional dyspnea.Support or Funding InformationThe study was funded by (FAPESP: 2017/07771‐3). L.C.A. and T.O.F received CAPES scholarships. I.C.R received a FAPESP scholarship.