Cerebral ATP and Lactate Levels in the Squirrel Monkey Following Occlusion of the Middle Cerebral Artery

Abstract

Previous studies have shown that occlusion of the middle cerebral artery (MCA) of the squirrel monkey results in a consistent large infarct; that in the initial two hours after occlusion of the MCA, blood flow in the central area of ischemia continues at a reduced rate (20% to 50% of normal); and that restoration of normal flow within three hours results in a survival rate of 65% without infarction. In this study, cerebral adenosine triphosphate (ATP), lactate, and pyruvate concentrations were measured at various time intervals after occlusion of the MCA. ATP decreased slowly during a three-hour period to 30% of normal, and lactate, after an initial rapid accumulation, increased slowly to about eight times normal. This compares to the effects of circulatory arrest which, in the dog, results in a reduction of the ATP level to 25% of normal within four minutes and a reciprocal increase in the lactate level. Because the effects of total cerebral anoxia are potentially reversible prior to four minutes, and, therefore, at an ATP concentration above 25% of normal, the slow rate of ATP depletion observed in the ischemic monkey brain supports the view that a significant period exists after occlusion of a major intracranial vessel wherein the ischemic effects are potentially reversible. Using the methods of this study, future investigations should permit a meaningful evaluation of the relative merits of those measures recommended for the treatment of acute cerebral ischemia.