title: Reducing cerebral blood flow increases the duration of electroencephalographic silence by intracarotid thiopental.
abstract: The effects of IV anesthetics are enhanced by increased cerebral blood flow (CBF) because of a greater delivery of drugs to the brain. In contrast, mathematical simulations suggest that a decrease in CBF, by increasing regional drug uptake and decreasing drug washout, enhances the efficacy of intraarterial drugs. We hypothesized that administrating intracarotid anesthetics during cerebral hypoperfusion will significantly prolong the duration of electroencephalographic (EEG) silence. We tested our hypothesis on New Zealand White rabbits. In the first group of 7 animals, we observed that decreasing CBF by approximately 70% attenuated, but did not abolish, EEG activity. Subsequently, 9 animals received 3 intracarotid injections of 3 mg of thiopental (thiopental-1, thiopental + hypoperfusion, and thiopental-2). The first and third injections were made under physiological conditions. The second drug injection was made during cerebral hypoperfusion. Compared with injection of thiopental-1 and -2, thiopental + hypoperfusion resulted in a profound increase in EEG silence (from 45 +/- 5 and 67 +/- 27 s, to 206 +/- 46 s, respectively, n = 9, P < 0.0001). The EEG recovery profile was similar during all three thiopental challenges. The study suggests that modulation of CBF is an important tool for enhancing intraarterial drug delivery to the brain.
authors.affiliation: Departments of *Anesthesiology, †Radiology, and ‡Neurosurgery, College of Physicians and Surgeons of Columbia University, New York, New York.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Joshi
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Etu
authors.forename: John
authors.initials: J
authors.lastname: Pile-Spellman
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D017536:Carotid Artery, Common / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004569:Electroencephalography / Q000187:drug effects*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D011412:Propanolamines / Q000494:pharmacology; D011817:Rabbits; D013874:Thiopental / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D006993:Hypnotics and Sedatives; D011412:Propanolamines; D014665:Vasodilator Agents; D013874:Thiopental; D000241:Adenosine; C036604:esmolol