Multitracer Pet Studies in Mcao of Cats as a Model for Acute Ischemic Stroke

Abstract

Repeat studies in animal models of acute focal ischemia may shed light on the development of changes causing ischemic infarcts or recovery of critically per-fused tissue. Regional cerebral blood flow, cerebral metabolic rate for oxygen, oxygen extraction fraction, cerebral metabolic rate of glucose, and flumazenil (FMZ) binding were studied repeatedly by positron-emission tomography (PET) in the cat middle cerebral artery occlusion (MCAO) model. After permanent MCAO the development of dense ischemia (misery perfused) penumbral tissue and its centrifugal conversion to necrosis could be demonstrated, with the chance of recovery if collateral perfusion developed spontaneously within the first hours after MCAO. With transient MCAO, reperfusion was effective only in preventing infarction when it was initiated as long as misery perfusion persisted: In these cases tissue was salvaged, and large infarcts did not develop. In other instances, when oxygen metabolism broke down and an increased oxygen extraction fraction was not longer seen, reperfusion even at levels above preocclusion had no effect, and large space-occupying infarcts developed. Under these circumstances FMZ uptake as a marker of neuronal integrity was decreased, indicating irreversible neuronal damage. Whereas repetitive MCAO of 10 min duration (six episodes, 60 min of ischemia in total) only slightly impaired energy metabolism, occlusions of 20 min (three episodes) caused severe metabolic derangement and infarcts comparable to those seen with 60 min of uninterrupted ischemia. These results demonstrate that PET studies in the cat ischemia model can help to explain various courses and diverging outcomes of acute ischemic stroke. The extrapolation of these data to comparable findings obtained during early stroke may affect the selection of appropriate therapeutic strategies.