Butanediol induced cerebral protection from ischemic-hypoxia in the instrumented Levine rat.
To determine if 1,3-Butanediol (BD), which protects mice from hypoxia, would extend the tolerance of rats to ischemic-hypoxia, the Levine rat (unilateral carotid ligation and conscious hypoxic exposure) was modified to record mean arterial pressure (BP), heart rate (HR), central venous pressure (CVP), spontaneous respiration and EEG. Age and weight matched, male, Sprague-Dawley rats were anesthetized under halothane (1-2%), ligated, instrumented, and recovered 2 hrs before hypoxia (4.5% oxygen). Thirty minutes prior to hypoxia, groups of rats received, BD (47 mmoles/kg i.v.; n = 7), equal volumes of saline (S) (n = 6) or no-infusion (NI) (n = 7). Since no significant difference was observed between S and NI they were combined into a single control group (C). In a parallel group administered BD, resultant beta- hydroxybutarate ( BHB ) levels increased from 0.13 +/- 0.02 to 0.84 +/- 0.03 mM and temperature declined only 1.5 degrees C. The EEG of all ischemic-hypoxic rats invariably became isoelectric before cessation of spontaneous respiration and eventual loss of BP. BD significantly (p less than 0.01, Student's t) increased ischemic-hypoxic tolerance (time to isoelectric EEG) from 875 +/- 56 for the control group to 1338 +/- 67 seconds for the BD group, without changing the interval from isoelectric EEG to loss of BP. Further, EEG activity persisted at a lower mean BP (p less than 0.01) in the BD group (44 +/- 5 mm Hg) than in the control group (66 +/- 4 mm Hg). In summary, isoelectric EEG invariably precedes ventilatory failure and cardiovascular collapse. BD increases ischemic-hypoxic tolerance in the conscious rat by extending, at a lower mean BP, the time to isoelectric EEG.
D020155:3-Hydroxybutyric Acid; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D002072:Butylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D002496:Central Venous Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004569:Electroencephalography; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006885:Hydroxybutyrates / Q000097:blood; D000860:Hypoxia / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects
D002072:Butylene Glycols; D006885:Hydroxybutyrates; C028491:1,3-butylene glycol; D020155:3-Hydroxybutyric Acid