Impact of pulmonary system limitations on locomotor muscle fatigue in patients with COPD

Abstract

We examined the effects of respiratory muscle work [inspiratory (W(r-insp)); expiratory (W(r-exp))] and arterial oxygenation (Sp(O(2))) on exercise-induced locomotor muscle fatigue in patients with chronic obstructive pulmonary disease (COPD). Eight patients (FEV, 48 +/- 4%) performed constant-load cycling to exhaustion (Ctrl; 9.8 +/- 1.2 min). In subsequent trials, the identical exercise was repeated with 1) proportional assist ventilation + heliox (PAV); 2) heliox (He:21% O(2)); 3) 60% O(2) inspirate (hyperoxia); or 4) hyperoxic heliox mixture (He:40% O(2)). Five age-matched healthy control subjects performed Ctrl exercise at the same relative workload but for 14.7 min ( approximately best COPD performance). Exercise-induced quadriceps fatigue was assessed via changes in quadriceps twitch force (Q(tw,pot)) from before to 10 min after exercise in response to supramaximal femoral nerve stimulation. During Ctrl, absolute workload (124 +/- 6 vs. 62 +/- 7 W), W(r-insp) (207 +/- 18 vs. 301 +/- 37 cmH(2)O x s x min(-1)), W(r-exp) (172 +/- 15 vs. 635 +/- 58 cmH(2)O x s x min(-1)), and Sp(O(2)) (96 +/- 1% vs. 87 +/- 3%) differed between control subjects and patients. Various interventions altered W(r-insp), W(r-exp), and Sp(O(2)) from Ctrl (PAV: -55 +/- 5%, -21 +/- 7%, +6 +/- 2%; He:21% O(2): -16 +/- 2%, -25 +/- 5%, +4 +/- 1%; hyperoxia: -11 +/- 2%, -17 +/- 4%, +16 +/- 4%; He:40% O(2): -22 +/- 2%, -27 +/- 6%, +15 +/- 4%). Ten minutes after Ctrl exercise, Q(tw,pot) was reduced by 25 +/- 2% (P < 0.01) in all COPD and 2 +/- 1% (P = 0.07) in healthy control subjects. In COPD, DeltaQ(tw,pot) was attenuated by one-third after each interventional trial; however, most of the exercise-induced reductions in Q(tw,pot) remained. Our findings suggest that the high susceptibility to locomotor muscle fatigue in patients with COPD is in part attributable to insufficient O(2) transport as a consequence of exaggerated arterial hypoxemia and/or excessive respiratory muscle work but also support a critical role for the well-known altered intrinsic muscle characteristics in these patients.

Fig. 1.

Operating lung volumes at rest and during whole body control exercise. A and B: within-group changes of end-expiratory (EELV) and end-inspiratory (EILV) lung volumes during constant-load cycling at the same relative exercise intensity [chronic obstructive pulmonary disease (COPD) group, A; age-matched Healthy-Control group, B]. At any given time point during the constant-load exercise performed at different absolute exercise intensities (62 ± 7 W and 124 ± 6 W for COPD and Healthy-Control, respectively), EELV and EILV are substantially lower in the Healthy-Control group (P < 0.05). TLC, total lung capacity. Vt, tidal volume; IC_dyn, dynamic inspiratory capacity. C: between-group differences in EILV and EELV between patients with COPD and Healthy-Control subjects at any given minute ventilation (V̇e).

Fig. 2.

Inspiratory (W_r-insp) and expiratory (W_r-exp) muscle work during constant-load exercise (62 ± 7 W and 124 ± 6 W for COPD and Healthy-Control, respectively). A and B: difference between COPD and Healthy-Control for inspiratory (A) and expiratory (B) muscle pressure-time product [esophageal pressure (P_es) × respiratory frequency (f_R)] during control (Ctrl) exercise at the same relative workload (52 ± 2% of W_peak). C and D: for COPD group, effects of various interventions on W_r-insp (C) and W_r-exp (D) during exercise at the identical workload (62 ± 7 W). Pressure-time products for the inspiratory and expiratory muscles were calculated by integrating P_es over the period of inspiratory or expiratory flow and then multiplying the integral by f_R. PAV, proportional assist ventilation.

Fig. 3.

W_r-insp (A) and W_r-exp (B) at any given V̇e in COPD patients (●) and Healthy-Control subjects (○).

Fig. 4.

Potentiated quadriceps twitch force expressed as a percentage of preexercise baseline before and 10 and 35 min after exercise. Preexercise baseline values were 167 ± 7 N and 149 ± 16 N for COPD group (n = 8) and Healthy-Control group (n = 5), respectively (P = 0.30). A: individual fatigue data for both subject groups under control conditions. B: group mean fatigue data under various conditions. +P < 0.05 from Healthy-Ctrl; *P < 0.05 from COPD-Ctrl and Healthy-Ctrl; #not significantly different from preexercise baseline.