Theophylline-induced recovery in a hemidiaphragm paralyzed by hemisection in rats: contribution of adenosine receptors.

Previously, we demonstrated that a single intravenous injection of theophylline can induce recovery in a hemidiaphragm paralyzed by cervical (C2) spinal cord hemisection for up to 3 h. The present study contrasts the actions of enprofylline and theophylline on inducing hemidiaphragmatic recovery after cervical spinal cord hemisection. Both drugs are methylxanthines; however, theophylline is an adenosine receptor antagonist while enprofylline is not. To further test the involvement of adenosine receptors, N6 (L-2-phenylisopropyl) adenosine (L-PIA), an analogue of adenosine was used in conjunction with theophylline. Following a left C2 spinal cord hemisection, animals were injected with either enprofylline (2.5-20 mg/kg) or theophylline (15 mg/kg) alone or in combination. Theophylline-injected animals demonstrated robust respiratory-related activity in the previously quiescent left phrenic nerve and hemidiaphragm. No recovery was observed in any of the enprofylline-injected rats. When enprofylline injection was followed later with theophylline, recovery occurred. Prior L-PIA administration blocked theophylline-induced recovery. When given after theophylline, L-PIA attenuated and then blocked the induced activity in both the nerve and hemidiaphragm ipsilateral to spinal cord hemisection. We conclude that adenosine receptor antagonism is implicated in hemidiaphragmatic recovery after hemisection and theophylline may be useful in the treatment of spinal cord injured patients with respiratory deficits.