Transgenic Alzheimer Mice Have a Larger Minimum Alveolar Anesthetic Concentration of Isoflurane than Their Nontransgenic Littermates

Abstract

More than 12% of all people older than 65 yr have Alzheimer's disease. Because nothing is known about changes in demand of volatile anesthetics in this disease, we determined minimum alveolar anesthetic concentration (MAC) values of isoflurane in young and aged transgenic mice at risk of developing Alzheimer's disease (heterozygote APP23 mice with the "Swedish double mutation"). To differentiate between unspecific effects of the transgenic model and specific Alzheimer effects, we additionally evaluated MAC values in mice with the same genetic construct but without the Alzheimer's disease-causing Swedish double mutation (heterozygote APP51/16 mice). MAC was determined in 60 mice (10 per group): heterozygote APP23 mice and their wild type littermates at the age of 4 and 18 mo, respectively, and heterozygote APP51/16 mice and their wild type littermates at the age of 18 mo. Anesthesia was induced with isoflurane in oxygen/air. The concentration of inhaled isoflurane varied between 1.0 and 2.0 Vol%, and the motor reaction to toeclamping was recorded. Means of the MAC values were compared with an unpaired t-test. The MAC of 18-mo-old heterozygote APP23 mice was 1.67 +/- 0.09, i.e., 9% larger than the MAC of their wild type littermates (1.53 +/- 0.14; P = 0.020). Heterozygote APP51/16 mice had a lower MAC than their wild type littermates (1.32 +/- 0.14 vs 1.48 +/- 0.13; P = 0.037). All wild type groups and young heterozygote APP23 mice had comparable MAC values. The increased MAC value in aged heterozygote APP23 mice seems to be attributable to changes related to Alzheimer's disease.