Aminophylline increases parasternal intercostal muscle activity during hypoxia in humans

To clarify the mechanism of action of aminophylline on the hypoxic ventilatory response in humans, we analyzed the effects of aminophylline on respiratory neural output. To evaluate the respiratory neural output, we analyzed the electromyogram (EMG) of the parasternal intercostal muscle, one of the major inspiratory muscles, in eight healthy subjects. Both before and during aminophylline administration, measurements of ventilatory parameters with EMG recordings were conducted in room air, mild hypoxia (FIO2FIO2 0.15), and severe hypoxia (FIO2FIO2 0.11). Before administering aminophylline, hypoxic stimulation elicited ventilatory augmentation in a hypoxia-intensity dependent manner. Administration of aminophylline caused significant increases in ventilation (V˙I), tidal volume (VT), respiratory frequency (fR), and the respiration-related phasic moving averaged EMG amplitude (tidal EMG), at corresponding levels of hypoxia compared to before aminophylline. Augmentation patterns of hypoxia-induced increases in VT and tidal EMG showed close similarity. These results indicate that augmentation of hypoxic ventilatory response by aminophylline is mainly mediated by an increase in the respiratory neural drive in healthy humans.