Relationship between plasma glucose, brain lactate, and intracellular pH during cerebral ischemia in gerbils.
The dose-response relation between plasma glucose and brain lactate and the relation of these parameters to intracellular pH during severe cerebral ischemia have not been well characterized over a wide range of plasma glucose levels. Experiments to delineate these relations in the gerbil model of global ischemia were performed by using phosphorus-31 nuclear magnetic resonance spectroscopy to measure intracellular pH and a new method to measure brain lactate. Ischemia increased final brain lactate linearly 4 mumol/g for every 100 mg/dl increase in plasma glucose up to 650 mg/dl (p = 0.0001, r2 = 0.9); beyond 650 mg/dl, saturation of the glucose transport-glycolysis system occurred. Plasma glucose correlated better with ischemic intracellular pH than did brain lactate. However, when brain lactate levels are compared with intracellular pH during ischemia, the relation may be threshold rather than linear. A narrow transition zone, during which ischemic intracellular pH decreased precipitously with increasing brain lactate, was observed between 17 and 22 mumol/g; below 17 mumol/g, intracellular pH remained stable at 6.8-6.9, whereas above 22 mumol/g, intracellular pH decreased maximally to about 6.2. The marked decrease in intracellular pH that occurs when brain lactate surpasses 17 mumol/g suggests that this sudden drop in intracellular pH may account for the "lactate threshold" for increased cerebral ischemic damage.
Combs
D J
DJ
Department of Surgery and Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington.
Dempsey
R J
RJ
Maley
M
M
Donaldson
D
D
Smith
C
C
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005849:Gerbillinae; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010758:Phosphorus
D001786:Blood Glucose; D007773:Lactates; D010758:Phosphorus