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The brain is assumed to be the site of anesthetic action, but anesthetics have effects elsewhere, such as the spinal cord. A preferentially anesthetized goat brain model was used to determine the importance of anesthetic action in the brain.Six goats were anesthetized with isoflurane; after tracheal intubation and insertion of a femoral arterial catheter, bilateral neck dissections were performed to isolate the external carotid arteries and external jugular veins. The occipital arteries were ligated to prevent vertebral blood from entering the carotid system. (Goats do not have direct, significant vertebral artery contributions to the brain, and they lack internal jugular veins.) Control Isoflurane minimum alveolar concentration (MAC) was determined using a dew-claw clamp as the painful stimulus. Following this, cranial venous blood was drained into a bubble oxygenator in which an isoflurane vaporizer was placed in line with the gas flow. Oxygenator arterial isoflurane concentration was estimated from the Isoflurane partial pressure in the oxygenator exhaust. Isoflurane administration via the lungs was discontinued and the isoflurane partial pressure in the blood delivered via the carotid artery was Increased by an amount required to bracket the partial pressures permitting and preventing movement in response to dew-claw stimulation. The native circulation was reestablished and MAC determined again.Cerebral Isoflurane requirements were 1.2 ± 0.3% (mean ± SD) before bypass, increased to 2.9 ± 0.7% during bypass when the brain was preferentially anesthetized, and decreased to 1.3 ± 0.1% after bypass.The results support the importance of sub-cortical structures, such as the spinal cord, in the generation of purposeful movement in response to a painful stimulus under general anesthesia.