Effect of blood pH and ischemia on kinetic constants for cerebral glucose transport.
In 117 experiments, the isolated canine brain was subjected either to 4-min pulses with blood ranging from pH 6.8 to 7.8, 30 min of hypoxia (PaO2 30 mmHg or 40 mmHg), or 30 min of complete ischemia followed by 60 min of perfusion with normal oxygenated blood. Unidirectional and net glucose fluxes were measured under all experimental conditions, and kinetic constants were calculated for unidirectional transport at each pH and after ischemia. In brains perfused with blood having a PaO2 of 30 or 40 mmHg, we observed a 58 and a 55% increase, respectively, in the net flux; however, there was no significant change in the unidirectional flux either during hypoxia or during the recovery period. Exposure of the brains to blood with a pH of 6.8, 7.0, and 7.2 had no effect on the unidirectional flux; however, as pH was raised above 7.4 both the Km and Vmax increased, reaching a maximum of 12.06 +/- 2.34 mM and 2.38 +/- 0.28 mumol X g-1 X min-1, respectively, at pH 7.8. The V/K ratio was unchanged. After 30 min of ischemia, there was a significant change (P less than 0.05) in the Km of the unidirectional glucose transport process from a control value of 5.84 +/- 1.75 mM to 17.40 +/- 5.50. These studies suggest that unidirectional flux is impaired after ischemia due to a decrease in the carrier's affinity for glucose; however, the observed changes are apparently unrelated to a fall in tissue pH. A similar mechanism is believed to be responsible for the decrease in unidirectional glucose flux after hypoxia.
D000818:Animals; D001693:Biological Transport, Active; D001769:Blood / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000503:physiopathology*; D004285:Dogs; D004569:Electroencephalography; D005947:Glucose / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010477:Perfusion
D001786:Blood Glucose; D005947:Glucose