Muscle Mechanoreflex Control of Ventilation and Inspiratory Drive in Patients with Chronic Obstructive Pulmonary Disease

Abstract

IntroductionActivation of mechano‐ and metabo‐sensitive skeletal muscles afferents contributes to the regulation of exercise hyperpnea in healthy humans. Patients with chronic obstructive pulmonary disease (COPD) commonly have skeletal muscle dysfunction, which is likely accompanied by alteration in reflex ventilatory responses mediated by activation of skeletal muscle afferents.ObjectiveTo investigate the effect of muscle mechanoreflex activation on ventilation and inspiratory drive in patients with COPD.MethodsThirty four patients with COPD (FEV1 = 48 ± 13% predicted, mean ± SEM) and 20 age‐ and sex‐matched healthy controls participated in the study. Muscle mechanoreceptors were activated by passive knee flexion and extension of the dominant leg. The passive movement was performed at 0.5 Hz for 30 s using an isokinetic dynamometer. Each trial was repeated at least four times. Superficial electrical activity of the vastus lateralis was monitored to confirm the absence of active contractions. Respiratory flow was continuously measured via a differential pressure pneumotachometer. Inspiratory flow (i.e., tidal volume divided by inspiratory time) and superficial electrical activity of the parasternal intercostals multiplied by the respiratory frequency (EMGpara index) provided proxies of the inspiratory drive. All data were interpolated to 1‐s intervals, time‐aligned across repetitions, and ensemble averaged. Baseline data were compared by the Student's t‐test. Responses to passive movement (Δ = passive movement minus baseline) were analyzed via two‐way repeated measures ANOVA, followed by Fisher's post hoc test. Data are reported as mean ± SEM. Statistical significance was set at P < 0.05.ResultsAt rest, patients with COPD presented higher ventilation, inspiratory flow and EMGpara index in comparison with controls. Passive movement increased ventilation, via increase in breathing frequency, as well as increased inspiratory flow and EMGpara index in both groups. However, patients with COPD presented blunted ventilatory (ΔCOPD = 0.527 ± 0.149 vs. Δcontrols = 1.099 ± 0.194 L/min, P = 0.01) and inspiratory flow (ΔCOPD = 0.011 ± 0.007 vs. Δcontrols = 0.036 ± 0.009 L/s, P = 0.03) responses during the first 10 s of the passive movement as compared to controls. The EMGpara index tended to be higher in patients with COPD at this time point (P = 0.06). During the final 10 s of the passive movement, the ventilatory response was similar between groups, whereas inspiratory flow (ΔCOPD = 0.061 ± 0.008 L/s vs. Δcontrols = 0.024 ± 0.011 L/s, P < 0.01) and EMGpara index (ΔCOPD = 54 ± 9 vs. Δcontrols = 24 ± 13 a.u., P = 0.046) responses were greater in patients with COPD as compared to controls.ConclusionsPatients with COPD had a slower ventilatory response and a higher inspiratory drive response to muscle mechanoreflex activation. The results suggest that the muscle mechanoreflex control of ventilation and inspiratory drive is abnormal in COPD which may be involved in the generation of exercise‐related dyspnea.Support or Funding InformationThe study was funded by (FAPESP: 2017/07771‐3). L.C.A. received a scholarship (CAPES).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.