ACTIONS OF SYSTEMIC THEOPHYLLINE ON HEMIDIAPHRAGMATIC RECOVERY IN RATS FOLLOWING CERVICAL SPINAL-CORD HEMISECTION

This study assesses the effects of theophylline on enhancing phrenic n erve discharge and functional hemidiaphragmatic recovery after C2 spin al cord hemisection in adult female rats. There were three separate gr oups of spinal hemisected rats and one nonhemisected group studied. Tw enty-four hours following C2 spinal hemisection, ipsilateral phrenic n erve activity was recorded under standardized, normoxic and then hypox ic conditions. After 30 min, theophylline was administered and the rec ordings were repeated in group 1 animals. In group 2, activity in both phrenic nerves was recorded simultaneously before and after drug admi nistration. In a third group of rats, both ipsilateral phrenic nerve a nd hemidiaphragmatic activities were monitored before and after the dr ug. In control nonhemisected animals under standardized recording cond itions, the effects of theophylline were quantitatively assessed by de termining the mean area under integrated phrenic nerve discharge wavef orms before and after drug administration. Generally, theophylline ind uced biphasic effects; i.e., at a low dose (15 mg/kg) it evoked excita tion, while at a high dose (30 mg/kg) depression of respiratory activi ty predominated. In group 2 animals, respiratory activity was induced in the nerve ipsilateral to the hemisection and enhanced in the contra lateral phrenic nerve for up to 3 h after a single standard dose of th eophylline (15 mg/kg). Prior to drug administration, there was an abse nce of respiratory-related activity in both the phrenic nerve and hemi diaphragm ipsilateral to C2 spinal cord hemisection. A standard dose o f theophylline, however, induced recovery of activity in both the phre nic nerve and the left hemidiaphragm ipsilateral to the hemisection in group 3 animals. In control (nonhemisected) animals, theophylline enh anced phrenic nerve activity, but decreased the duration of respirator y bursts. These results show for the first time that theophylline can activate latent respiratory motor pathways and thus restore the respir atory drive to phrenic motoneurons lost by spinal cord injury. Respira tory activity is not only reestablished in the phrenic nerve made quie scent by hemisection, but it is also enhanced in the contralateral phr enic nerve. The drug also restores function to the hemidiaphragm paral yzed by the spinal cord hemisection. The findings may have clinical re levance to human cases of cervical spinal cord injury in which respira tory function is compromised. (C) 1996 Academic Press, Inc.