THEOPHYLLINE AND HYPOXIC VENTILATORY RESPONSE IN THE RAT ISOLATED BRAIN-STEM-SPINAL CORD

We have used the isolated brainstem-spinal cord preparation of the neo natal rat to study the effects of theophylline on the ventilatory resp onse to hypoxia. The brainstem-spinal cord was isolated from neonatal rats (0-4 days) and superfused with mock cerebrospinal fluid (CSF), eq uilibrated with a gas mixture (F-O2, 0.90; F-CO2, 0.02; F-N2, 0.08; co ntrol CSF) at 27 degrees C. We recorded phrenic nerve discharge from C 4 roots, using suction electrodes, and measured respiratory ratory fre quency (fR) and the amplitude of the integrated phrenic neurogram (int egral phr). We examined how theophylline and the specific adenosine an tagonist, 8-p-sulfophenyltheophylline (SPT), modify the ventilatory re sponse to hypoxia. The response during superfusion with hypoxic CSF (F -02, 0.06) consisted of a marked decrease in fR (to 60 % of control) a nd a slight decline in integral phr (to 85 % 6 of control). By contras t, in the presence of theophylline (30 mg/L = 165 mu M) and SPT (5 mg/ L = 15 mu M) in the superfusate hypoxia reduced fR only moderately (to 87% of control) and exerted virtually no effect on integral phr (105% of control). Theophplline and SPT attenuated the rate of decrease in fR and completely blocked the decrease in integral phr. There was no d ifference between the effects of theophylline and those of SPT. The re sults suggest that theophylline attenuates hypoxic respiratory depress ion, and that this effect is mediated by the blockade of adenosine.