Cerebral Acidosis in Focal Ischemia: I. A Method for the Simultaneous Measurement of Local Cerebral pH with Cerebral Glucose Utilization or Cerebral Blood Flow in the Rat

We developed a technique for the simultaneous autoradiographic determination of local cerebral pH (LCpH) using [¹⁴C]dimethyloxazolidinedione ([¹⁴C)DMO) with either local cerebral glucose utilization (LCGU) using [¹⁴C]deoxyglucose ([¹⁴C]DG) or local CBF (LCBF) using [¹⁴C]iodoantipyrine ([¹⁴C]IAP). The method evolved from the observation that [¹⁴C]DMO is “unstable,” which is shown here to be due to sublimation of the compound. Thus, the technique consists of administering to rats [¹⁴C]DMO followed by either [¹⁴C]DG or [¹⁴C]IAP. The first autoradiographic film that results contains both labeled compounds. The brain sections are then exposed in a fume hood until the complete disappearance of [¹⁴C]DMO, which usually required 10 days. The second film thus contains only the non-DMO isotope administered. Blood levels of the two isotopes are calculated from the total concentrations of isotope and the rate of decline of [¹⁴C]DMO in blood. This information is then used to determine cerebral pH and the other cerebral function of interest. Using this double-label technique in normal rats, LCpH, LCGU, and LCBF can be determined with the same accuracy as with single-label techniques. In rats with middle cerebral artery occlusion, this technique yielded LCpH and LCBF values 4 h after occlusion that were not statistically different from those obtained by separate determinations. Thus, interactions between LCpH and either LCBF or LCGU can be studied by this technique in normal and pathological conditions.