Repeat Positron Emission Tomographic Studies in Transient Middle Cerebral Artery Occlusion in Cats: Residual Perfusion and Efficacy of Postischemic Reperfusion

Abstract

Summary:The wider clinical acceptance of thrombolytic therapy for ischemic stroke has focused more attention on experimental models of reversible focal ischemia. Such models enable the study of the effect of ischemia of various durations and of reperfusion on the development of infarc tions. We used high-resolution positron emission tomo graphy (PET) to assess cerebral blood flow (CBF), cere bral metatfolic rate of oxygen (CMR02), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose (CMRglc) before, during, and up to 24 h after middle cere bral artery occlusion (MCAO) in cats. After determination of resting values, the MCA was occluded by a transorbital device. The MCA was reopened after 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 surviving the first day, infarct size was determined on serial histologic sections. The arterial occlusion immedi ately reduced CBF in the MCA territory to <40% of con trol, while CMROz was less affected, causing an increase in OEF. Whereas in the cats surviving 24 h of reperfusion after 60-and 120-min MCAO, OEF remained elevated throughout the ischemic episode, the initial OEF increase had already disappeared during the later period of ischemia in those cats that died during the reperfusion period. After and CMRglc, large infarcts developed, and intracranial pres sure increased fatally. In those surviving the day after MCAO, increased OEF persisted over the ischemic epi sode, postischemic hyperperfusion was less severe and shorter, and the perfusional and metabolic defects as well as the final infarcts were smaller. These results stress the importance of the severity of ischemia for the further course after reperfusion and help to explain the diverging outcome after thrombolysis, where a relation between the residual flow and the effectiveness of reperfusion was also observed.

Mapping the dynamics of brain perfusion using functional ultrasound in a rat model of transient middle cerebral artery occlusion

“…Classic PET studies in cats subjected to 30-120 min MCAo also showed that acute post-clip release hyperperfusion was associated with worse tissue outcome. 37 Another frequently observed post-MCAo phenomenon, also not observed here, is delayed hypoperfusion, i.e. a secondary drop in perfusion following early complete reperfusion.…”

Early Basal Ganglia Hyperperfusion on CT Perfusion in Acute Ischemic Stroke: A Marker of Irreversible Damage?

“…A "luxury perfusion syndrome" characterized by overabundant CBF relative to neuronal and glial metabolic demand is wellknown. 8,9 Much of our knowledge of postischemic reperfusion is derived from experimental models, 14 but the finding that postischemic hyperperfusion may include brain regions that become infarcted has also been demonstrated in small studies of human patients with stroke. 6 In 1 study of patients with stroke who underwent large-vessel recanalization with intra-arterial fibrinolysis, hyperperfusion was demonstrated in 5/12 by perfusion MR imaging several hours after recanalization.…”

Perioperative Neuroprotection Symposium

“…The ability of astrocytes to maintain these functions may, in fact, be a critical determinant of neuronal survival after ischemia (Aschner et al, 1999;Juurlink, 1997;Marrif and Juurlink, 1999;Stanimirovic etal, 1997). Furthermore, metabolic imaging studies have suggested that mitochondrial function in post-ischemic brain may be impaired for hours to days after the ischemic insult (Heiss et al, 1997;Hoehn-Berlage, 1995;Ogasawara et al, 2001;Takamatsu et al, 2000;Wardlaw et al, 1998). Loss of f m and eventual energy failure in astrocytes might lead to an inability to provide these critical support functions during ischemia, thus exacerbating ischemic injury to neurons.…”