Butanediol Induced Cerebral Protection from Ischemic-Hypoxia in the Instrumented Levine Rat

SUMMARY To determine if 1,3-Butanediol (BD), which protects mice from hypoxia, would extend the tolerance of rats to ischemlc-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 EEC 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 NT 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°C. The EEG of all ischemlc-hypoxic rats invariably became isoelectric before cessation of spontaneous respiration and eventual loss of BP. BD significantly (p < 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 < 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.