Middle cerebral artery occlusion and reperfusion in primates monitored microdialysis and sequential positron emission tomography

Background and Purpose-In a previous investigation concerning the hemodynam ic and metabolic changes over time displayed by sequential positron emissio n tomography (PET) in a middle cerebral artery (MCA) occlusion/reperfusion primate model, a metabolic threshold for irreversible ischemia could be ide ntified (reduction of metabolic rate of oxygen [CMRO2] to approximate to 60 % of the contralateral hemisphere). To evaluate the potential of microdialy sis (MD) as an instrument for chemical brain monitoring, the aim of this su bsequent study was to relate the chemical changes in MD levels directly to the regional metabolic status (CMRO2 above or below the metabolic threshold ) and the occurrence of reperfusion, as assessed by PET. Methods-Continuous MD (2 probes in each brain) and sequential PET measureme nts were performed during MCA occlusion (2 hours) and 18 hours (mean) of re perfusion in 8 monkeys (Macaca mulatta). Energy-related metabolites (lactat e, pyruvate, and hypoxanthine) and glutamate were analyzed. The MD probe re gions were divided into 3 categories on the basis of whether CMRO2 was belo w Or above 60% of the contralateral region (metabolic threshold level) duri ng MCA occlusion and whether;reperfusion was obtained: severe ischemia with reperfusion (n=4), severe ischemia without reperfusion (n=4), and penumbra with reperfusion (n=5). Results-The lactate/pyruvate ratio, hypoxanthine, and glutamate showed simi lar patterns. MD probe regions with severe ischemia and reperfusion and pro be regions with severe ischemia and no reperfusion displayed high and broad peaks, respectively, during MCA occlusion, and the levels almost never dec reased to baseline. Penumbra MD probe regions displayed only slight transie nt increases during MCA occlusion and returned to baseline. Conclusions-This experimental study of focal ischemia showed that the extra cellular changes of energy-related metabolites and glutamate differed depen ding on the ischemic state of the brain during MCA occlusion and depending on whether reperfusion occurred. If MD proves to be beneficial in clinical practice, it appears important to observe relative changes over time.