CEREBRAL AMINES AND ACUTE HYPERBARIC OXYGEN TOXICITY

¹ Center for Cerebral Vascular Research and the Departments of Medicine and Pharmacology, Duke University Medical Center and Veterans Administration Hospital, Durham, North Carolina

Acute central nervous system (CNS) toxicity impedes treatment with hyperbaric oxygen (OHP) for ischemic illness and led to this study of relationships between cerebral amines and OHP-induced CNS toxicity in rats after injection of selected drugs. Brain levels of norepinephrine and serotonin were unchanged after 1 hr of OHP at 4.95 atmospheres absolute. However, injection of pargyline (40-60 mg/kg), a monoamine oxidase (MAO) inhibitor, 30 mm prior to OHP (4.95 atmospheres absolute) exposure for 2.5 hr increased (54%) the latent period before the onset of convulsions, decreased the frequency of convulsions from 92 to 33% and increased 72-hr survival from 20 to 59% (n = 66). Iproniazid (25-75 mg/kg) proved equally effective; isoniazid (50-100 mg/kg), an analog lacking MAO inhibitory activity, was ineffective. Although inhibitors of norepinephrine synthesis (-methyl-p-tyrosine, 100 mg/kg) and of 5-hydroxytryptamine synthesis (dl-p-chlorophenylalanine, 300 mg/kg) lowered respective amine levels without changing OHP tolerance, the protective action of pargyline remained unaltered. Amine precursors 5-hydroxytryptophan (10-25 mg/kg) and 3,4-dihydroxyphenylalanine (25-50 mg/kg) also failed to alter oxygen tolerance. Our data indicate that premedication with certain MAO inhibitors can protect rats from OHP-induced CNS toxicity. These studies suggest that both the CNS toxicity induced by hyperbaric oxygen and the protection from toxicity afforded by certain MAO inhibitors are not mediated through alterations in the brain metabolism of norepinephrine and 5-hydroxytryptamine.

This article has been cited by other articles:

				J. H. Zhang, A. B. Singhal, and J. F. Toole Oxygen Therapy in Ischemic Stroke Stroke, September 1, 2003; 34 (9): e152 - e153. [Full Text] [PDF]