Anoxic cerebral potassium accumulation reduced by phenytoin: mechanism of cerebral protection?

Abstract

Results from a previous study suggested that the cerebral protective effect of phenytoin (PNT) might be linked to its ability to reduce cerebrospinal fluid potassium (K+) accumulation during anoxia. In the present study two PNT doses (50 and 150 mg/kg) were examined to determine the ability of PNT to reduce cerebrospinal fluid K+ in cisterna magna samples after 10 and 20 minutes of circulatory arrest. Also examined were two other protective treatments (pentobarbital, 33 mg/kg, and hypothermia to 35 C) which, in the hypoxic (F1O2 = 0.05) mouse, provide cerebral protection equivalent to PNT, 50 mg/kg. Both PNT doses significantly reduced cerebrospinal fluid K+ accumulation and tended to do so in a dose-related manner, similar to the dose-related cerebral protective effect of PNT. PNT, 50 mg/kg reduced K+ accumulation more effectively than either pentobarbital or hypothermia, whose protective effects are likely explained by a different mechanism (i.e., reduced cerebral metabolic rate). These data support the hypothesis that PNT-induced cerebral protection may be linked to its effect on cerebral K+ accumulation.

• Authors: A A Artru, J D Michenfelder
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 60 Issue 1 Pg. 41-5 (Jan 1981) ISSN: 0003-2999 [Print] United States
• PMID: 7192948 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Phenytoin
• Pentobarbital
• Potassium

Topics

• Animals
• Cisterna Magna
• Dose-Response Relationship, Drug
• Heart Arrest (metabolism)
• Hypothermia, Induced
• Hypoxia, Brain (metabolism)
• Pentobarbital (pharmacology)
• Phenytoin (administration & dosage, pharmacology)
• Potassium (cerebrospinal fluid)
• Rabbits