Effects of isoflurane versus fentanyl-nitrous oxide anesthesia on long-term outcome from severe forebrain ischemia in the rat.
BACKGROUND
This study examined long-term outcome from severe forebrain ischemia in the rat, as a function of anesthetic given during the ischemic injury.


METHODS
Rats were subjected to 10 min of near-complete forebrain ischemia while anesthetized with either 1.4% isoflurane or 70% nitrous oxide-fentanyl. Neurologic and histologic outcomes were measured at 5 days, 3 weeks, or 3 months after ischemia.


RESULTS
At 5 days, isoflurane-anesthetized rats had less damage than did fentanyl-nitrous oxide-anesthetized rats (mean +/- SD, percent alive hippocampal CA1 neurons = 58+/-29 vs. 20+/-16, respectively; P = 0.011). This was accompanied by improved motor function in the isoflurane group (P = 0.002). At 3 weeks, there was no difference between groups for either outcome variable (percent alive CA1 neurons = 35+/-26 and 36+/-28 for isoflurane and fentanyl-nitrous oxide, respectively). Similarly, at 3 months, there was no difference between groups (percent alive CA1 neurons = 56+/-27 and 60+/-27 for isoflurane and fentanyl-nitrous oxide, respectively). Morris water maze performance at 3 months was similar between anesthetic groups and was also similar to sham performance. The percent alive CA1 neurons in the fentanyl-nitrous oxide group increased with duration of recovery (P = 0.004). There were no differences among isoflurane groups over time (5 days vs. 3 weeks, P = 0.26; 5 days vs. 3 months, P = 0.99; 3 week vs. 3 months, P = 0.32).


CONCLUSIONS
This study found no change in the percent alive CA1 hippocampal neurons as a function of duration of recovery from severe forebrain ischemia in isoflurane anesthetized rats. In contrast, the percent alive CA1 neurons in fentanyl-nitrous oxide-anesthetized rats tripled over 3 months of recovery. The natural history of long-term responses to forebrain ischemia requires further study before conclusions can be drawn with respect to the permanence of isoflurane neuroprotection.
Elsersy
Hazem
H
The Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, North Carolina, USA.
Sheng
Huaxin
H
Lynch
John R
JR
Moldovan
Maria
M
Pearlstein
Robert D
RD
Warner
David S
DS
D000758:Anesthesia / Q000379:methods; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D005283:Fentanyl / Q000494:pharmacology / Q000627:therapeutic use*; D007530:Isoflurane / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009609:Nitrous Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D016548:Prosencephalon / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013995:Time
D007530:Isoflurane; D009609:Nitrous Oxide; D005283:Fentanyl