REPEAT POSITRON EMISSION TOMOGRAPHIC STUDIES IN TRANSIENT MIDDLE CEREBRAL-ARTERY OCCLUSION IN CATS - RESIDUAL PERFUSION AND EFFICACY OF POSTISCHEMIC REPERFUSION

The wider clinical acceptance of thrombolytic therapy for ischemic str oke has focused more attention on experimental models of reversible fo cal ischemia. Such models enable the study of the effect of ischemia o f various durations and of reperfusion on the development of infarctio ns. We used high-resolution positron emission tomography (PET) to asse ss cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2 ), oxygen extraction fraction (OEF), and cerebral metabolic rate of gl ucose (CMRglc) before, during, and up to 24 h after middle cerebral ar tery occlusion (MCAO) in cats, After determination of resting values, the MCA was occluded by a transorbital device. The MCA was reopened af ter 30 min in five, after 60 min in 11, and after 120 min in two cats. Whereas all cats survived 30-min MCAO, six died after 60-min and one after 120-min MCAO during 6-20 h of reperfusion. In those cats survivi ng the first day, infarct size was determined on serial histologic sec tions. The arterial occlusion immediately reduced CBF in the MCA terri tory to <40% of control, while CMRO2 was less affected, causing an inc rease in OEF. Whereas in the cats surviving 24 h of reperfusion after 60- and 120-min MCAO, OEF remained elevated throughout the ischemic ep isode, the initial OEF increase had already disappeared during the lat er period of ischemia in those cats that died during the reperfusion p eriod. After 30-min MCAO, the reperfusion period was characterized by a transient reactive hyperemia and fast normalization of CBF, CMRO2, a nd CMRglc, and no or only small infarcts in the deep nuclei were found in histology, After 60- and 120-min MCAO: the extent of hyperperfusio n was related to the severity of ischemia, decreased CMRO2 and CMRglc persisted, and cortical/subcortical infarcts of varying sizes develope d, A clear difference was found in the flow/metabolic pattern between surviving and dying cats: In cats dying during the observation period, extended postischemic hyperperfusion accompanied large defects in CMR O2 and CMRglc, large infarcts developed, and intracranial pressure inc reased fatally. In those surviving the day after MCAO, increased OEF p ersisted over the ischemic episode, postischemic hyperperfusion was le ss severe and shorter, and the perfusional and metabolic defects as we ll as the anal infarcts were smaller. These results stress the importa nce of the severity of ischemia for the further course after reperfusi on and help to explain the diverging outcome after thrombolysis, where a relation between the residual flow and the effectiveness of reperfu sion was also observed.