Bicarbonate conservation during incomplete cerebral ischemia with superimposed hypercapnia

We superimposed extreme hypercapnia (arterial PCO₂ 400-450 mmHg) immediately before and during incomplete cerebral ischemia to distinguish the role of intracellular pH (pH(i)) and bicarbonate ([HCO₃^-](i)) in postischemic metabolic and electrophysiological recovery. Incomplete global ischemia was produced in seven anesthetized dogs by 30 min of intracranial hypertension followed by 4 h of reperfusion. ATP, phosphocreatine (PCr), and pH(i) were measured with ³¹P magnetic resonance spectroscopy, and [HCO₃^-](i) was calculated from the Henderson-Hasselbalch equation using the measured pH(i) and sagittal sinus PCO₂. Cerebral blood flow was reduced to 7 ± 1 ml·min^-1·100 g^-1 (± SE) during ischemia with extreme hypercapnia, and pH(i) decreased to 5.72 ± 0.09. During normocapnic reperfusion, pH(i) rapidly returned to near baseline values by 14 min. [HCO₃^-](i) fell from 12.1 ± 0.9 to 6.0 ± 1.2 mM by the midpoint of ischemia and recovered by 30 min of reperfusion. ATP, PCr, and O₂ consumption also recovered rapidly and completely. Somatosensory-evoked potentials (SEP) recovered to 43 ± 10% of control amplitude. These results are in marked contrast to the poor metabolic and SEP recovery previously observed in hyperglycemic dogs in which pH(i) decreased to the same range as with hypercapnic ischemia, but in which [HCO₃^-](i) was much lower (1.1 ± 0.5 mM). Therefore, [HCO₃^-](i) depletion during hyperglycemic ischemia may be a more important factor in recovery than end-ischemic pH(i) per se. We speculate that higher [HCO₃^-](i) may improve glial cell buffering capacity or decrease iron availability for hydroxyl radical production.