Severe hypotension is not essential for isoflurane neuroprotection against forebrain ischemia in mice.
BACKGROUND
Volatile anesthetics provide protection in experimental models of global cerebral ischemia. To date, all models evaluated have included profound systemic arterial hypotension as a component of the ischemic insult. This study was designed to determine if isoflurane protection persists in a global insult devoid of hypotension.


METHODS
C57BL/6J mice having a high incidence of posterior communicating artery atresia were anesthetized with isoflurane (1.2%) or fentanyl/N2O and subjected to bilateral carotid artery occlusion for 15 min or 20 min with normotension (80-110 mmHg mean arterial pressure) or for 10 min with hypotension (35 mmHg mean arterial pressure). Three days later, neurologic function and histologic damage were assessed. Other mice underwent measurement of intraischemic cerebral blood flow (4-iodo-N-methyl-[14C]antipyrine autoradiography) or plasma norepinephrine.


RESULTS
Isoflurane reduced the percentage of hippocampal CA1 dead neurons (e.g., 10 min bilateral carotid occlusion + hypotension: 43 +/- 18 (isoflurane) vs. 67 +/- 20 (fentanyl/N2O), P = 0.003; 20 min bilateral carotid occlusion + normotension: 49 +/- 27 (isoflurane) vs. 71 +/- 22 (fentanyl/N2O), P = 0.003). Isoflurane also reduced CA3 damage and improved neurologic function under all conditions. Intraischemic forebrain blood flow was similar during bilateral carotid occlusion plus normotension for the two anesthetic states. Plasma norepinephrine values were greater when hypotension was added to the ischemic insult.


CONCLUSIONS
Isoflurane resulted in improved neurologic function and reduced histologic damage regardless of the presence or absence of systemic hypotension during the ischemic insult. This indicates that beneficial effects of isoflurane are most likely attributable to direct effects at the neuronal level as opposed to indirect effects resulting from interactions with profound hypotension.
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
H Mayumi
HM
Homi
Javier M
JM
Mixco
Huaxin
H
Sheng
Hilary P
HP
Grocott
Robert D
RD
Pearlstein
David S
DS
Warner
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology*; D007023:Hypotension, Controlled; D007091:Image Processing, Computer-Assisted; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents; D009638:Norepinephrine / Q000378:metabolism
D018685:Anesthetics, Inhalation; D018696:Neuroprotective Agents; D007530:Isoflurane; D009638:Norepinephrine