The characterization of tissue acid-base status related to the penumbral zone of increased glucose consumption surrounding a focal cerebral ischemic lesion may suggest therapeutic techniques to maximize tissue survivability from stoke. We measured local cerebral metabolic rate for glucose (1 CMRglc) and an index of brain tissue pH (pHt) concurrently and characterized their interaction in a model of focal cerebral ischemia in rats in a double-label autoradiographic study, using [14C]2-deoxyglucose and [14C]dimethyloxazolidinedione. Computer-assisted digitization and analysis permitted the simultaneous quantification of the two variables on a pixel-by-pixel basis in the same brain slices. Hemispheres ipsilateral to intravascular tamponade-induced middle cerebral artery occlusion showed areas of normal, depressed, and elevated glucose metabolic rate (as defined by an interhemispheric asymmetry index) after 2 hr of ischemia. Regions of increased 1 CMRglc showed moderate acidosis (6.87 +/- 0.05), while regions of normal glucose metabolic rate showed normal pHt (pH +/- SD = 6.98 +/- 0.05) and regions of decreased 1 CMRglc showed severe acidosis (6.69 +/- 0.11). A repeated-measures analysis of variance found these values to differ from each other at the P less than 0.0005 significance level. The finding of moderate acidosis coupled with increased 1 CRMglc in the metabolic penumbra suggests that the excess protons may result from the anaerobic dissociation of ATP synthesis and hydrolysis.

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The pathogenesis of brain injury or dysfunction following hypoxic or ischemic episodes is an issue of considerable importance. The neurochemical re sponses to hypoxia and ischemia are complex, and a number of authors have suggested that anaerobic metabolism of exogenous glucose to form lactic acid is a critical element in determining whether permanent cerebral injury occurs. This hypothesis dates to reports of Myers and Yamaguchi (1977) in which cardiac arrest during hyperglycemia was as sociated with more extensive neurological injury than cardiac arrest during normoglycemia. Rehn crona et al. (1980) found that if the lactate concen- tration exceeded 20-25 mmol/kg, recovery to a nor mal energy state was precluded. Subsequent re ports have supported this hypothesis (Siesj6, 1985;Rehncrona, 1986).The effects of hypoxia on glucose metabolism are more complex than the commonly held belief that anaerobic glycolysis causes acidosis owing to the hydrolysis of lactic acid. Gevers (1977) pointed out that the production of lactate itself does not lead to an obligatory co-production of hydrogen ions and a fall in pH, since the net products of anaerobic gly colysis are two lactate ions and two MgATp 2 -ions.Acidosis is caused by the concurrent net hydrolysis of ATP, which produces two H+ ions. Although the net reaction of anaerobic glycolysis, ATP hydroly sis, and synthesis, always yields two lactate ions and two H+ ions from each glucose molecule, the concentration of dissociated hydrogen ions is af fected by the pH of the reaction system, the mag nesium ion concentration, and the substrate (glu cose or glycogen) (Hochachka and Mommsen,

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