Respiratory muscle function and activation in chronic obstructive pulmonary disease.

Inspiratory muscles are uniquely adapted for endurance, but their function is compromised in chronic obstructive pulmonary disease (COPD) due to increased loads, reduced mechanical advantage, and increased ventilatory requirements. The hyperinflation of COPD reduces the flow and pressure-generating capacity of the diaphragm. This is compensated by a threefold increase in neural drive, adaptations of the chest wall and diaphragm shape to accommodate the increased volume, and adaptations of muscle fibers to preserve strength and increase endurance. Paradoxical indrawing of the lower costal margin during inspiration in severe COPD (Hoover's sign) correlates with high inspiratory drive and severe airflow obstruction rather than contraction of radially oriented diaphragm fibers. The inspiratory muscles remain highly resistant to fatigue in patients with COPD, and the ultimate development of ventilatory failure is associated with insufficient central drive. Sleep is associated with reduced respiratory drive and impairments of lung and chest wall function, which are exaggerated in COPD patients. Profound hypoxemia and hypercapnia can occur in rapid eye movement sleep and contribute to the development of cor pulmonale. Inspiratory muscles adapt to chronic loading with an increased proportion of slow, fatigue-resistant fiber types, increased oxidative capacity, and reduced fiber cross-sectional area, but the capacity of the diaphragm to increase ventilation in exercise is compromised in COPD. In COPD, neural drive to the diaphragm increases to near maximal levels in exercise, but it does not develop peripheral muscle fatigue. The improvement in exercise capacity and dyspnea following lung volume reduction surgery is associated with a substantial reduction in neural drive to the inspiratory muscles.

Neurobiology of exercise.

Voluntary physical activity and exercise training can favorably influence brain plasticity by facilitating neurogenerative, neuroadaptive, and neuroprotective processes. At least some of the processes are mediated by neurotrophic factors. Motor skill training and regular exercise enhance executive functions of cognition and some types of learning, including motor learning in the spinal cord. These adaptations in the central nervous system have implications for the prevention and treatment of obesity, cancer, depression, the decline in cognition associated with aging, and neurological disorders such as Parkinson's disease, Alzheimer's dementia, ischemic stroke, and head and spinal cord injury. Chronic voluntary physical activity also attenuates neural responses to stress in brain circuits responsible for regulating peripheral sympathetic activity, suggesting constraint on sympathetic responses to stress that could plausibly contribute to reductions in clinical disorders such as hypertension, heart failure, oxidative stress, and suppression of immunity. Mechanisms explaining these adaptations are not as yet known, but metabolic and neurochemical pathways among skeletal muscle, the spinal cord, and the brain offer plausible, testable mechanisms that might help explain effects of physical activity and exercise on the central nervous system.

Diaphragm length and neural drive after lung volume reduction surgery.

RATIONALE: Patients with chronic obstructive pulmonary disease have shorter inspiratory muscles and higher motor unit firing rates during quiet breathing than do age-matched healthy subjects. Lung volume reduction surgery (LVRS) in patients with chronic obstructive pulmonary disease improves lung function, exercise capacity, and quality of life. OBJECTIVES: We studied the effect of LVRS on length and motor unit firing rates of diaphragm and scalene muscles. METHODS: Diaphragm length was estimated by ultrasound and magnetometers, and firing rates were recorded with needle electrodes in patients (five females and seven males) with severe chronic obstructive pulmonary disease, before and after surgery. MEASUREMENTS AND MAIN RESULTS: Pre-LVRS total lung capacity was 135 +/- 10% predicted (mean +/- SD), and FEV1 was 30 +/- 12% predicted. After surgery, median firing frequency of diaphragmatic motor units fell from 17.3 +/- 4.2 to 14.5 +/- 3.4 Hz (p < 0.001), and scalene motor unit firing rates were reduced from 15.3 +/- 6.9 to 13.4 +/- 3.8 Hz (p < 0.001). Tidal volume and diaphragm length change during quiet breathing did not change, but at end expiration, the zone of apposition length of diaphragm against the rib cage (L(Zapp)) increased (30 +/- 28%, p = 0.004). Improvements in quality-of-life measures and exercise performance after surgery were related to increased forced vital capacity and L(Zapp). CONCLUSIONS: Increased diaphragm length resulted in lower motor unit firing rates and reduced breathing effort, and this is likely to contribute to improved quality of life and exercise performance after LVRS.