Penumbral tissue alkalosis in focal cerebral ischemia: Relationship to energy metabolism, blood flow, and steady potential

The effect of focal ischemia on tissue pH was studied at various times up to 6 hours after permanent middle cerebral artery occlusion in rats. Tissue pH was imaged by using umbelliferone fluorescence and correlated with cerebral blood flow, ATP content, and recordings of the steady potential. Circumscribed foci of alkalosis (pH 7.32 ± 0.11) were detected with increasing frequency in penumbral regions having near-to-normal ATP concentrations and cerebral blood flow values between 20% and 40% of control. Both the infarct core, defined by ATP loss and cerebral blood flow values of less than 20% of control, and the inner peri-infarct rim were consistently acidic (pH 6.03 ± 0.36 and 6.53 ± 0.24, respectively). Treatment with the glutamate antagonist dizocilpine (MK-801) suppressed negative shifts of the steady potential and reduced significantly the occurrence of alkalosis observed in 90% of untreated but only in 44% of treated animals. Penumbral alkalosis appeared to be a time-dependent event occurring 30 to 60 minutes after the passage of peri-infarct depolarizations. The diversity of penumbral pH changes reflects the local disturbance of pH regulation and, possibly, the differential fate of penumbral subareas. Ann Neurol 2000;47:485–492.