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We evaluated whether contractile fatigue of the quadriceps occurs after cycling exercise in patients with chronic obstructive pulmonary disease (COPD) and whether it could contribute to exercise limitation. Eighteen COPD patients performed two constant work-rate cycling exercises up to exhaustion. These tests were preceded by nebulization of placebo or 500 microg of ipratropium bromide. Muscle fatigue was defined as a postexercise reduction in quadriceps twitch force of more than 15% of the resting value. There was an increase in endurance time postipratropium compared with placebo nebulization (440 +/- 244 seconds vs. 322 +/- 188 seconds, p = 0.06). Nine patients developed contractile fatigue after placebo exercise. In these patients, ipratropium did not increase the endurance time (394 +/- 220 seconds with placebo vs. 400 +/- 119 seconds with ipratropium) despite an 11% improvement in FEV1. In the nine patients who did not fatigue after placebo exercise, endurance time increased from 249 +/- 124 seconds with placebo to 479 +/- 298 seconds with ipratropium (p < 0.05). There was a significant correlation between the improvement in endurance time with ipratropium and quadriceps twitch force at 10 minutes after placebo exercise (r = 0.59, p = 0.01). The occurrence of contractile fatigue during exercise may explain why bronchodilation fails to improve exercise tolerance in some COPD patients.