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NEUROSURGICAL ANESTHESIA

Endotoxin Augments Cerebral Hyperemic Response to Halothane by Inducing Nitric Oxide Synthase and Cyclooxygenase

Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin

Address correspondence and reprint requests to Anthony Hudetz, MD, PhD, Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226. Address e-mail to ahudetz{at}mcw.edu

We examined the cerebral hyperemic response to halothane after treatment with bacterial lipopolysaccharide (LPS). To determine the involvement of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), we tested whether the effect of LPS on halothane-induced hyperemia was altered by pretreatment with the selective iNOS inhibitor, aminoguanidine (100 mg/kg), COX-2 inhibitor, NS-398 (5 mg/kg), or enzyme expression inhibitor, dexamethasone (4 mg/kg). Further, we examined whether the administration of a nitric oxide donor, diethylamine NONOate, would change the cerebral hyperemic response of halothane. Sprague-Dawley rats were anesthetized with 0.5 minimum alveolar anesthetic concentration of halothane and artificially ventilated. Regional cerebrocortical blood flow (rCBF) was assessed by laser-Doppler flowmetry. LPS (1 mg/kg) was administered intracerebroventricularly; artificial cerebrospinal fluid was used in controls. Four hours after LPS infusion, iNOS and COX-2 messenger ribonucleic acid (mRNA) levels (reverse transcription-polymerase chain reaction) and enzyme activities (arginine-citrulline conversion and prostaglandin E₂ enzyme immunoassay) were significantly increased. LPS enhanced halothane-induced 3.9 and 1.6-fold increases in rCBF at 1.0 and 1.5 minimum alveolar concentration, respectively. Co-treatment with NS-398 attenuated, but aminoguanidine or dexamethasone abolished the effect of LPS on halothane-induced rCBF increase. Diethylamine NONOate mimicked the enhanced rCBF response to halothane. These results suggest that LPS augmented halothane-induced cerebrocortical hyperemia by induction of iNOS and COX-2.

Implications: Excess nitric oxide and prostaglandins after lipopolysaccharide treatment in the brain augment halothane-induced increases in cerebral blood flow.

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				K. Nagase and K. Ando-Nagase Endotoxin Augments Cerebral Hyperemic Response to Halothane by Inducing Nitric Oxide Synthase Anesth. Analg., April 1, 2001; 92(4): 1075 - 1075. [Full Text] [PDF]