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NEUROSURGICAL ANESTHESIA

Effects of Isoflurane, Ketamine, and Fentanyl/N₂O on Concentrations of Brain and Plasma Catecholamines During Near-Complete Cerebral Ischemia in the Rat

Neuroanesthesia Research Laboratory, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina

Address correspondence to David S. Warner, MD, Department of Anesthesiology, Box 3094, Duke University Medical Center, Durham, NC 27710. Address e-mail to warne002{at}mc.duke.edu

We postulated that adrenergic responses to global cerebral ischemia are anesthetic-dependent and similar in both brain and arterial blood. Rats were anesthetized with isoflurane (1.4%), ketamine (1 mg · kg^-1 · min^-1), or fentanyl (25 µg · kg^-1 · h^-1)/70% N₂O. The carotid arteries were occluded for either 20 min with mean arterial pressure (MAP) 50 mm Hg (incomplete ischemia) or 10 min with MAP 30 mm Hg (near-complete ischemia). Norepinephrine was measured in hippocampal microdialysate. Norepinephrine and epinephrine were measured in arterial plasma. In both hippocampus and plasma, basal norepinephrine was similar among anesthetics. During incomplete ischemia, hippocampal norepinephrine was twofold greater with fentanyl/N₂O than with isoflurane (P = 0.037), but plasma norepinephrine and epinephrine were similar and unchanged among all three anesthetics. During near-complete ischemia, hippocampal norepinephrine was threefold greater with ketamine than fentanyl/N₂O (P = 0.005), whereas plasma norepinephrine and epinephrine were markedly greater with fentanyl/N₂O than with ketamine (P < 0.0005) or isoflurane (P = 0.05). There was no correlation between norepinephrine concentrations in hippocampus and plasma for either incomplete or near-complete ischemia. This study demonstrates that adrenergic responses to global ischemia are anesthetic-dependent, particularly during more severe insults. The absence of a correlation between plasma and brain catecholamine concentrations indicates that adrenergic responses to ischemia are independent in brain and blood.

Implications: It has been proposed that anesthetics modulate cerebral ischemic outcome by influencing peripheral adrenergic responses to ischemia. This experiment demonstrates that anesthetics differentially modulate adrenergic responses to ischemia but that effects in plasma and brain are independent. This suggests that events detected in the peripheral circulation do not implicate direct mechanisms of action of catecholamines at the neuronal/glial level.

This article has been cited by other articles:

				K. Engelhard, C. Werner, W. E. Hoffman, B. Matthes, M. Blobner, and E. Kochs The Effect of Sevoflurane and Propofol on Cerebral Neurotransmitter Concentrations During Cerebral Ischemia in Rats Anesth. Analg., October 1, 2003; 97(4): 1155 - 1161. [Abstract] [Full Text] [PDF]

				E. Marana, M. G. Annetta, F. Meo, R. Parpaglioni, M. Galeone, M. L. Maussier, and R. Marana Sevoflurane improves the neuroendocrine stress response during laparoscopic pelvic surgery: [Le sevoflurane ameliore la reaction neuro-endocrinienne au stress pendant une intervention chirurgicale laparoscopique pelvienne] Can J Anesth, April 1, 2003; 50(4): 348 - 354. [Abstract] [Full Text] [PDF]

				B. Nellgard, G. B. Mackensen, G. Massey, R. D. Pearlstein, and D. S. Warner The Effects of Anesthetics on Stress Responses to Forebrain Ischemia and Reperfusion in the Rat Anesth. Analg., July 1, 2000; 91(1): 145 - 151. [Abstract] [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999