Effects of isoflurane, ketamine, and fentanyl/N2O on concentrations of brain and plasma catecholamines during near-complete cerebral ischemia in the rat

We postulated that adrenergic responses to global cerebral ischemia are ane sthetic-dependent and similar in both brain and arterial blood. Rats were a nesthetized with isoflurane (1.4%), ketamine (1 mg.kg(-1).min(-1)), or fent anyl (25 mu g.kg(-1).h(-1))/70% N2O. The carotid arteries were occluded for either 20 min with mean arterial pressure (MAP) 50 mm Hg (incomplete ische mia) or 10 min with MAP 30 mm Hg (near-complete ischemia). Norepinephrine w as measured in hippocampal microdialysate. Norepinephrine and epinephrine w ere measured in arterial plasma. in both hippocampus and plasma, basal nore pinephrine was similar among anesthetics. During incomplete ischemia, hippo campal norepinephrine was twofold greater with fentanyl/N2O than with isofl urane (P = 0.037), but plasma norepinephrine and epinephrine were similar a nd unchanged among all three anesthetics. During near-complete ischemia, hi ppocampal norepinephrine was threefold greater with ketamine than fentanyl/ N2O (P = 0.005), whereas plasma norepinephrine and epinephrine were markedl y greater with fentanyl/N2O than with ketamine (P < 0.0005) or isoflurane ( P = 0.05). There was no correlation between norepinephrine concentrations i n hippocampus and plasma for either incomplete or near-complete ischemia. T his study demonstrates that adrenergic responses to global ischemia are ane sthetic-dependent, particularly during more severe insults. The absence of a correlation between plasma and brain catecholamine concentrations indicat es that adrenergic responses to ischemia are independent in brain and blood . Implications: It has been proposed that anesthetics modulate cerebral isc hemic outcome by influencing peripheral adrenergic responses to ischemia. T his experiment demonstrates that anesthetics differentially modulate adrene rgic responses to ischemia but that effects in plasma and brain are indepen dent. This suggests that events detected in the peripheral circulation do n ot implicate direct mechanisms of action of catecholamines at the neuronal/ glial level.