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 t o 6 hours after permanent middle cerebral artery occlusion in rats. Tissue pH was imaged by using umbelliferone fluorescence and correlated with cereb ral blood flow, ATP content, and recordings of the steady potential. Circum scribed 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 now values between 20% and 40% of control. Both the infarct core, defined by ATP loss and cerebral blood now values of less than 20% o f 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 an tagonist dizocilpine (MK-801) suppressed negative shifts of the steady pote ntial and reduced significantly the occurrence of alkalosis observed in 90% of untreated but only in 44% of treated animals. Penumbral alkalosis appea red to be a time-dependent event occurring 30 to 60 minutes after the passa ge of peri-infarct depolarizations, The diversity of penumbral pH changes r eflects the local disturbance of pH regulation and, possibly, the different ial fate of penumbral subareas.