Attenuation of brain free fatty acid liberation during global ischemia: a model for screening potential therapies for efficacy?
Whole brain free fatty acids (FFA) continue to rise appreciably even 1 h after decapitation, which may reflect the evolution of ischemic brain injury at least during global ischemia. If so, the attenuation of FFA liberation by various drugs may reflect their efficacy in ischemic brain injury. Rats were pretreated with either 0.9% NaCl (controls), ketamine, halothane, lofentanil, etomidate, Y-9179, R41-468, Innovar-Vet, pentobarbital, thiopental, or phenytoin and decapitated 15 to 30 min thereafter. The brains were kept normothermic for 10 min until they were frozen in liquid nitrogen. Whole brain FFAs were quantitated gy gas-liquid chromatography. After 10 min of ischemia in controls, total FFAs and arachidonic, stearic, oleic, and palmitic acids increased by 8- to 10-fold. The drugs, in order of decreasing effectiveness in attenuating FFA liberation, fell into the following three groups: (1) phenytoin, thiopental, pentobarbital, and Innovar-Vet; (2) R41-468, Y-9179, and etomidate; and (3) lofentanil, halothane and ketamine. The three groups reduced total FFAs by about 23%, 13%, and 8%, respectively. The effectiveness of drugs in attenuating FFA liberation appears to correlate with their efficacy in ischemic brain injury. However, a cause and effect relationship between FAA liberation and the evolution of ischemic brain injury must be established before accurate predictions of efficacy can be made by this method. The limitations of the proposed method of evaluation are discussed.
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D003655:Decerebrate State; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000777:Anesthetics; D014150:Antipsychotic Agents; D005230:Fatty Acids, Nonesterified