Effect of theophylline on diaphragmatic and other skeletal muscle function

Methylxanthines and particularly caffeine are known to increase skeletal muscle contractility. Recently, it has been shown that theophylline improves diaphragmatic contractility of the respiratory muscles both in isolated muscle preparations and in animals and normal human beings. Furthermore, it has been demonstrated that theophylline reverses diaphragmatic fatigue and prevents fatigue of the diaphragm when it is given prophylactically. Finally, recent evidence indicates that theophylline improves diaphragmatic function in patients with chronic obstructive pulmonary disease, all of whom retained CO2 (PaCO2 43 +/- 3 mm Hg) and had hypoxia (PaO2 57 +/- 8 mm Hg). Patients both improved transdiaphragmatic pressure and were less susceptible to fatigue. These data strongly suggest that theophylline, which increases respiratory muscle strength and delays the onset of diaphragmatic fatigue, could be a very useful agent in the treatment of patients with chronic airway obstruction.