Dependence of cerebral energy phosphate and evoked potential recovery on end-ischemic pH

We determined whether the rate of metabolic recovery and electrophysiological deficit after incomplete cerebral ischemia is related to intracellular pH (pH(i)) achieved at the end of ischemia in a dose-dependent manner. End-ischemic pH(i) was varied by employing two ischemic durations, 12 and 30 min, and by setting preischemic plasma glucose to ~80 or 400 mg/dl. Incomplete global ischemia was produced in anesthetized dogs by transient intracranial hypertension followed by 4 h of reperfusion, and pH(i), ATP, and phosphocreatine (PCr) were measured with ³¹P magnetic resonance spectroscopy. Cerebral blood flow was reduced to ~6 ml·min^-1·100 g^-1 during ischemia. End-ischemic pH(i) was >5.7 in all animals from various treatment groups except for four of seven dogs treated with 30-min hyperglycemic ischemia. When end-ischemic pH(i) remained >5.7, there was nearly complete recovery of ATP, PCr, pH(i), intracellular bicarbonate concentration ([HCO₃^-](i)), and O₂ consumption. Partial recovery of somatosensory-evoked potentials (SEP) occurred in most of these animals. In the 30-min hyperglycemic animals in which pH(i) fell below 5.5, ATP, PCr, and O₂ consumption recovered by only one-half over 60 min of reperfusion and then declined to near-zero levels without SEP recovery. In addition, pH(i) remained <6.0, and [HCO₃^-](i) remained <2 mM throughout reperfusion. We conclude that there is an apparent in vivo pH(i) threshold of ~5.5-5.7 during incomplete cerebral ischemia that is associated with an inability to significantly restore pH(i) and [HCO₃^-](i) and with secondary deterioration of high-energy phosphate levels.