Group III and IV muscle afferents contribute to ventilatory and cardiovascular response to rhythmic exercise in humans

Abstract

We investigated the role of somatosensory feedback on cardioventilatory responses to rhythmic exercise in five men. In a double-blind, placebo-controlled design, subjects performed the same leg cycling exercise (50/100/150/325 ± 19 W, 3 min each) under placebo conditions (interspinous saline, L(3)-L(4)) and with lumbar intrathecal fentanyl impairing central projection of spinal opioid receptor-sensitive muscle afferents. Quadriceps strength was similar before and after fentanyl administration. To evaluate whether a cephalad migration of fentanyl affected cardioventilatory control centers in the brain stem, we compared resting ventilatory responses to hypercapnia (HCVR) and cardioventilatory responses to arm vs. leg cycling exercise after each injection. Similar HCVR and minor effects of fentanyl on cardioventilatory responses to arm exercise excluded direct medullary effects of fentanyl. Central command during leg exercise was estimated via quadriceps electromyogram. No differences between conditions were found in resting heart rate (HR), ventilation [minute ventilation (VE)], or mean arterial pressure (MAP). Quadriceps electromyogram, O(2) consumption (VO(2)), and plasma lactate were similar in both conditions at the four steady-state workloads. Compared with placebo, a substantial hypoventilation during fentanyl exercise was indicated by the 8-17% reduction in VE/CO(2) production (VCO(2)) secondary to a reduced breathing frequency, leading to average increases of 4-7 Torr in end-tidal PCO(2) (P < 0.001) and a reduced hemoglobin saturation (-3 ± 1%; P < 0.05) at the heaviest workload (∼90% maximal VO(2)) with fentanyl. HR was reduced 2-8%, MAP 8-13%, and ratings of perceived exertion by 13% during fentanyl vs. placebo exercise (P < 0.05). These findings demonstrate the essential contribution of muscle afferent feedback to the ventilatory, cardiovascular, and perceptual responses to rhythmic exercise in humans, even in the presence of unaltered contributions from other major inputs to cardioventilatory control.

Fig. 1.

Metabolic responses during the final minute of leg cycling exercise at 4 different workloads with (fentanyl) and without (placebo) partially blocked somatosensory neural feedback from the working locomotor muscles. A: O₂ consumption (V̇o₂). B: CO₂ production (V̇co₂). C: capillary lactate concentration. The ANOVA P value indicates the overall main effect of fentanyl.

Fig. 2.

Ventilatory response and hemoglobin saturation [arterial O₂ saturation by pulse oximetry (Sp_O2)] during the final minute of leg cycling exercise at 4 different workloads with (fentanyl, gray bars) and without (placebo, black bars) partially blocked somatosensory neural feedback from the working locomotor muscles. A: respiratory frequency (f_R). B: tidal volume (Vt). C: minute ventilation (V̇e). D: V̇e/V̇co₂. E: end-tidal Pco₂ (Pet_CO2). F: Sp_O2. The ANOVA P value indicates the overall main effect of fentanyl. *P < 0.05; ¹P = 0.08.

Fig. 3.

Identity plots to illustrate individual subject response at rest and during exercise under conditions of placebo and fentanyl. A: V̇e/V̇co₂. B: Pet_CO2. C: heart rate (HR). bpm, beats per minute. D: mean arterial blood pressure (MAP).

Fig. 4.

HR (A) and MAP (B) response during the final minute of leg cycling exercise at 4 different workloads without (Placebo) and with (Fentanyl) partially blocked somatosensory neural feedback from locomotor muscles. The P value indicates the overall main effect of fentanyl. *P < 0.05.

Fig. 5.

Myoelectrical activity [integrated EMG (iEMG)] of vastus lateralis muscle used to illustrate the similarity in the feedforward component (central neural drive) during the high constant-workload (325 ± 19 W) leg cycling trial with intact (Placebo) and partially blocked (Fentanyl) somatosensory afferent feedback. iEMG during each muscle contraction (cycle revolution) was calculated, averaged over each 60-s period, and normalized to the 1st minute of exercise. Pedal cadence was held constant (101 ± 5 rpm) throughout the exercise.