Post-ischemic brain tissue alkalosis suppressed by U74006F.
We monitored chronically (for 1 week) the effect of the 21-aminosteroid U74006F, a potent lipid peroxidation inhibitor, on the pH profile of the rat brain following transient forebrain ischemia. Eight rats were treated initially with 3 mg/kg i.v. of U74006F 1 min after reperfusion. A second dose of 1.5 mg/kg i.v. was given 60 min after reperfusion. A vehicle group (n = 9) was treated in the same manner, using the same volume of the vehicle solution, 20 mM citric acid, 3 mM sodium citrate, and 8 mM NaCl. Statistically significant interaction between group and time (P = 0.003) was detected for pH. Brain pH of the vehicle treated animals were significantly higher than the U74006F treated group at 24 h (P = 0.009) and 48 h (P = 0.009) of reperfusion. Chronic post-ischemic brain tissue alkalosis at 24 h (pH 7.22 +/- 0.12) and 48 h (pH 7.25 +/- 0.11) post-ischemia, observed among the vehicle treated animals (and untreated animals), was suppressed by treatment with U74006F. These results suggest a coupling between post-ischemic brain tissue alkalosis and free radical induced lipid peroxidation.
Vande Linde
A M
AM
Department of Neurology, Henry Ford Hospital, Detroit, MI 48202.
Chopp
M
M
Lee
S A
SA
Schultz
L R
LR
Welch
K M
KM
D000471:Alkalosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011281:Pregnatrienes / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D008054:Lipid Peroxides; D011281:Pregnatrienes; D005947:Glucose; C053355:tirilazad