IMPLICATIONS: Two hours of isoflurane anesthesia, with or without nitrous oxide, does not impair and may improve the ability of rats to acquire a novel spatial memory task 2 wk later.

Clinical studies indicate that anesthesia and surgery are associated with early cognitive impairment in both young and aged patients (1, 2). Recovery seems to be age-dependant, however, as only the aged suffer cognitive impairment lasting 3 mo or more (1, 2). In the laboratory, we have demonstrated that a 2-h anesthetic with 1.2% isoflurane (ISO)-70% nitrous oxide (N 2 O) attenuates performance improvement on a previously learned task in aged rats but improves performance in young adult rats (3). We found subsequently that acquisition of new spatial memory is impaired in both young and aged rats for 2–14 days after ISO+ N 2 O anesthesia and that this learning/memory impairment persists up to 28 days in aged rats (4, 5). We have not determined whether postanesthetic learning impairment persists in adult rats but, given the greater plasticity of the young brain and the fact that postoperative cognitive impairment is short-lived in young and middle aged patients, we speculated that postanesthetic spatial memory impairment resolves sooner in adult rats. To test this hypothesis, we evaluated acquisition of spatial memory in adult rats beginning 2 wk after general anesthesia.

Methods

This study was approved by the Standing Committee on the Use of Animals in Research and Teaching, Harvard University Faculty of Arts and Sciences. Thirty 6-mo old male Fischer 344 rats were acquired from the National Institute of Health Aged rat colony at Harlan and housed individually in a climate-and humidity-controlled room on a 12-h light: dark cycle with continuous access to food and water. After a 1-wk acclimation period, rats were randomly assigned (n= 10 per group) to receive 1.2% ISO-70% N 2 O-30% oxygen (ISO+ N 2 O), 1.8% ISO-30% oxygen (ISO), or 30% oxygen alone (control). Anesthesia was induced by placing rats in a chamber flushed with 3% ISO and 100% oxygen and intubating the trachea with a 14-gauge catheter. Rats were then mechanically ventilated with the appropriate anesthetic for 2 h with a 2-mL tidal volume delivered at a rate of 45 breaths/min, which pilot studies demonstrate maintains Paco 2 at 41.4±0.3 cm H 2 O (mean±sem) in 6-mo-old male Fischer 344 rats. Rectal temperature was controlled to 37 C±0.5 C. Arterial oxygen saturation and mean arterial blood pressure (MAP) were measured noninvasively using a pulse oximeter and a rat tail cuff during anesthesia. After 2 h, the anesthetics were discontinued and 100% oxygen was delivered. The rate of ventilation was reduced until spontaneous ventilation resumed and the trachea was extubated when the rat was responsive. Control rats were placed in a box flushed with 30% oxygen for 2 h and were not tracheally intubated. All animals were recovered for 30 min in a box flushed with 40% oxygen and then placed in their home cage.