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 gl obal ischemia, To determine whether isoflurane at a clinically relevant con centration is neuroprotective In a canine model of cardiac arrest, we measu red neurologic function and hippocampal Ca2+/calmodulin-dependent protein k inase 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 fibrillat ion. Animals were randomized to four groups: control, isoflurane-control, i schemia, 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 immunoblottin g, was measured by an Individual blinded to the treatment groups. CaMKII ac tivity was measured in samples from the cortex, hippocampus, and striatum o f 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) Hippocampa l levels of the <beta>-subunit of CaMKII (CaMKII beta) were relatively pres erved in isoflurane-ischemic animals (68 +/- 4% of control) compared with i schemic animals (48 +/- 2% of control; P < 0.001), although both groups wer e statistically significantly lower than control (P < 0.001 ischemia as. co ntrol and P < 0.05 isoflurane-ischemia Ds. control), Conclusions: Isoflurane Is an effective neuroprotective drug in a canine ca rdiac arrest model in terms of both functional and biochemical criteria.