The differential effects of equipotent doses of isoflurane and desflurane on hippocampal acetylcholine levels in young and aged rats.
The differential effects of age-adjusted equipotent doses of isoflurane (Iso) and desflurane (Des) on hippocampal acetylcholine (ACh) levels were examined using cerebral microdialysis in young (12-16 weeks old) and aged (16-18 months old) Fischer 344 rats. An 80min exposure to 1 minimum alveolar concentration (MAC) of isoflurane and desflurane produced similar maximal decreases in hippocampal ACh levels in both age groups: to 36.3+/-13.9% (Iso) and 28.6+/-12.9% (Des) of baseline in aged rats versus 32.5+/-18.7% (Iso) and 29.6+/-12.5% (Des) of baseline in young rats. Compared to isoflurane, the onset of this maximal decrease was delayed in both age groups with desflurane. Furthermore, following the end of anesthesia in aged rats, hippocampal ACh levels returned to control levels faster with desflurane (within 20-40min) than isoflurane (within 60-80min). These data demonstrate that age-adjusted equipotent doses of isoflurane and desflurane produce similar maximal decreases in hippocampal ACh levels in a manner that is independent of age. However, compared to isoflurane, desflurane is associated with a slower decrease in and a faster restoration of hippocampal ACh levels following anesthesia in this rat model of aging. Hence, in the aged, the administration of age-adjusted equipotent doses of an inhalational anesthetic with low blood and tissue solubility, such as desflurane, may provide a viable pharmacotherapeutic strategy for minimizing the duration of the attenuation of hippocampal cholinergic outflow observed following anesthesia.
Whittington
Robert A
RA
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 622 West 168th Street PH 5, New York, NY 10032, United States. raw9@columbia.edu <raw9@columbia.edu>
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D000109:Acetylcholine / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000077335:Desflurane; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012995:Solubility
D018685:Anesthetics, Inhalation; D000077335:Desflurane; D007530:Isoflurane; D000109:Acetylcholine