Isoflurane pretreatment ameliorates postischemic neurologic dysfunction and preserves hippocampal Ca2+/calmodulin-dependent protein kinase in a canine cardiac arrest model.
BACKGROUND
Inhalational anesthetics are neuroprotective in rat models of global ischemia. To determine whether isoflurane at a clinically relevant concentration is neuroprotective in a canine model of cardiac arrest, we measured neurologic function and hippocampal Ca2+/calmodulin-dependent protein kinase II (CaMKII) content 20 h after cardiac arrest.


METHODS
We tested the neuroprotective effect of 30 min of 1.5% isoflurane exposure before 8 min of global ischemia induced with ventricular fibrillation. Animals were randomized to four groups: control, isoflurane-control, ischemia, and isoflurane-ischemia. After resuscitation and 20 h of intensive care, each animal's neurologic deficit score was determined by two blinded evaluators. The hippocampal content of CaMKII, determined by immunoblotting, was measured by an individual blinded to the treatment groups. CaMKII activity was measured in samples from the cortex, hippocampus, and striatum of animals in each group.


RESULTS
Isoflurane-ischemic animals had a median neurologic deficit score of 22.6% compared with 43.8% for the ischemic animals (P < 0.05). Hippocampal levels of the beta-subunit of CaMKII (CaMKIIbeta) were relatively preserved in isoflurane-ischemic animals (68 +/- 4% of control) compared with ischemic animals (48 +/- 2% of control; P < 0.001), although both groups were statistically significantly lower than control (P < 0. 001 ischemia vs. control and P < 0.05 isoflurane-ischemia vs. control).


CONCLUSIONS
Isoflurane is an effective neuroprotective drug in a canine cardiac arrest model in terms of both functional and biochemical criteria.
Blanck
T J
TJ
Excitable Tissues Laboratory and the Department of Anesthesiology, Hospital for Special Surgery, New York, New York 10021, USA. blanckt@hss.edu
Haile
M
M
Xu
F
F
Zhang
J
J
Heerdt
P
P
Veselis
R A
RA
Beckman
J
J
Kang
R
R
Adamo
A
A
Hemmings
H
H
D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001927:Brain Diseases / Q000209:etiology / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D006339:Heart Rate / Q000187:drug effects; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology*; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy / Q000201:enzymology; D019194:Ischemic Preconditioning; D007530:Isoflurane / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D018685:Anesthetics, Inhalation; D018696:Neuroprotective Agents; D007530:Isoflurane; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium