SEQUENTIAL STUDIES OF SEVERELY HYPOMETABOLIC TISSUE VOLUMES AFTER PERMANENT MIDDLE CEREBRAL-ARTERY OCCLUSION - A POSITRON EMISSION TOMOGRAPHIC INVESTIGATION IN ANESTHETIZED BABOONS

Background and Purpose In the positron emission tomography literature, markedly hypometabolic brain tissue (oxygen metabolism < 1.3 to 1.7 m L . 100 g(-1). min(-1)) has often been equated with irreversible damag e in the human brain. By serial positron emission tomography measureme nts, we investigated the temporal evolution of the volume of severely hypometabolic brain tissue after permanent middle cerebral artery occl usion in anesthetized baboons with, as a perspective, the development of rational therapeutic strategies. Methods; Seven anesthetized and ve ntilated baboons underwent sequential positron emission tomography exa minations with the O-15 steady-state technique before and 1, 4, 7, and 24 hours and 14 to 29 days after occlusion. In each baboon the infarc t volume was calculated by quantitative histological procedures after 19 to 41 days of occlusion. Results The sequential measurement of regi onal oxygen metabolism demonstrated an extension (for greater than or equal to 24 hours) of the volume of severely hypometabolic tissue as d efined by both absolute and relative metabolic thresholds, and this pr ofile of evolutivity is observed no matter the threshold used. Mean (/- SEM) infarction volume of 2.4 +/- 0.6 cm(3) was comparable to a tis sue volume with oxygen consumption < 40% of contralateral metabolism. The volume of hypometabolic tissue was essentially stable at the 1-, 4 -, and 7-hour postocclusion studies, increased markedly at the 24-hour study point, and increased even further in the chronic-stage study (o n average, 17 days after occlusion). The tissue that eventually displa yed a severely hypometabolic state at the final measurement showed a s ignificant decrease of oxygen metabolism and cerebral blood how at eac h time analyzed. In that tissue, the oxygen extraction fraction increa sed significantly at 1 hour (although not thereafter). Conclusions The extension of severely hypometabolic volume after middle cerebral arte ry occlusion reinforces the concept of a dynamic penumbra and suggests the existence of a relatively large window of therapeutic opportunity in which it may be possible to develop neuroprotective strategies. Ou r study suggests that maximum infarct volume is determined at some tim e between 24 hours and 17 days after permanent middle cerebral artery occlusion in anesthetized baboons.