THEOPHYLLINE-INDUCED RECOVERY IN A HEMIDIAPHRAGM PARALYZED BY HEMISECTION IN RATS - CONTRIBUTION OF ADENOSINE RECEPTORS

Previously, we demonstrated that a single intravenous injection of the ophylline can induce recovery in a hemidiaphragm paralyzed by cervical (C2) spinal cord hemisection for up to 3 h. The present study contras ts the actions of enprofylline and theophylline on inducing hemidiaphr agmatic recovery after cervical spinal cord hemisection. Both drugs ar e methylxanthines; however, theophylline is an adenosine receptor anta gonist while enprofylline is not. To further test the involvement of a denosine receptors, N6 (L-2-phenylisopropyl) adenosine (L-PIA), an ana logue of adenosine was used in conjunction with theophylline. Followin g 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 co mbination. Theophylline-injected animals demonstrated robust respirato ry-related activity in the previously quiescent left phrenic nerve and hemidiaphragm. No recovery was observed in any of the enprofylline-in jected rats. When enprofylline injection was followed later with theop hylline, recovery occurred. Prior L-PIA administration blocked theophy lline-induced recovery. When given after theophylline, L-PIA attenuate d and then blocked the induced activity in both the nerve and hemidiap hragm ipsilateral to spinal cord hemisection. We conclude that adenosi ne receptor antagonism is implicated in hemidiaphragmatic recovery aft er hemisection and theophylline may be useful in the treatment of spin al cord injured patients with respiratory deficits. (C) 1998 Elsevier Science Ltd. All rights reserved.