Positron Emission Tomographic Measurement of Acute Hemodynamic Changes in Primate Middle Cerebral Artery Occlusion

Takahashi, Hiroshi; Ueda, Satoshi; Mizukawa, Nobuyoshi; Imahori, Yoshio; Hino, Akihiko; Ohmori, Yasuhiro; Yasukochi, K; Nakahashi, Hisamitsu; Wakita, Katsutoshi; Horii, Hiroyuki

doi:10.2176/nmc.32.805

Cited by 16 publications

(11 citation statements)

References 2 publications

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“…The absence of contralateral cerebral metabolic depression is in agree ment with the reports of Tenjin et al (1992) and Pappata et ai. (1993) infarction, while a lack of delayed metabolic changes las proposed by Andrews (1991)] might be explained by the relatively small infarcts obtained in the present study.…”

Section: Discussionsupporting

confidence: 93%

Relationships between High Oxygen Extraction Fraction in the Acute Stage and Final Infarction in Reversible Middle Cerebral Artery Occlusion: An Investigation in Anesthetized Baboons with Positron Emission Tomography

Young

Sette

Touzani

et al. 1996

J Cereb Blood Flow Metab

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Summary: Studies in humans suggest that regions that show maximal increases in brain oxygen extraction fraction (OEF) in the hours following an ischemic episode are those most vul nerable for infarction and are often, although not always, as sociated with the final site of infarction. To clarify this issue, we followed the hemodynamic and metabolic characteristics of regions with an initially maximally increased OEF and com pared them with the ultimately infarcted region in an experi mental stroke model. Positron emission tomography (PET) was used to obtain functional images of the brain prior to and fol lowing reversible unilateral middle cerebral artery occlusion (MCAO) in 11 anesthetized baboons. To model early reperfu sion, the clips were removed 6 h after occlusion. Successive measurements of regional CBF (rCBF), regional CMR02 (rCMR02), regional cerebral blood volume, and regional OEF (rOEF) were performed during the acute (up to 2 days) and chronic (> 15 days) stage. Late magnetic resonance imaging (MRI) scans (coregistered with PET) were obtained to identify infarction. Reversible MCAO produced an MRI-measurable infarction in 6 of II baboons; the others had no evidence of ischemic damage. Histological analysis confirmed the results of the MRI investigation but failed to show any evidence of cor tical ischemic damage. The lesion was restricted to the head of the caudate nucleus, internal capsule, and putamen. The infarct volume obtained was 0.58 ± 0.31 cm 3 . The infarcts were situ ated in the deep MCA territory, while the area of initially

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Section: Discussionsupporting

confidence: 93%

Relationships between High Oxygen Extraction Fraction in the Acute Stage and Final Infarction in Reversible Middle Cerebral Artery Occlusion: An Investigation in Anesthetized Baboons with Positron Emission Tomography

Young

Sette

Touzani

et al. 1996

J Cereb Blood Flow Metab

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show abstract

“…Re cent developments in functional imaging technolo gies enable such changes to be followed noninva sively even in small animals. With high-resolution pos itron emission tomography (PET), regional cerebral blood flow (rCBF), regional metabolic rate for oxy gen (rCMR02), and glucose (rCMRglc) can be mea sured repeatedly before and after occlusion of the middle cerebral artery (MCA) in baboons (Tenjin et a!., 1992;Pappata et a!., 1993) and in cats , and the development of the penumbra and the eventual progression to infarction can be followed. We have used repeat determinations of rCBF, rCMR02, and rCMRglc by PET in transient MCA occlusion (MCAO) and related the observed temporal and spatial patterns of changes in flow and energy metabolism to those observed in a few cases during and after thrombolytic therapy.…”

mentioning

confidence: 99%

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

Heiss

Graf

Löttgen

et al. 1997

J Cereb Blood Flow Metab

124

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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.

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“…Therefore, this scanner cannot be used for small experimental animals such as the rat or mouse. Clinical scanners, however, can be successfully applied to larger animals, such as the cat or the baboon, as demonstrated in our experiments and in other studies [32, 33]. The application of PET in experimental models of disease, e.g.…”

Section: Discussionmentioning

confidence: 66%

Relevance of Experimental Ischemia in Cats for Stroke Management: A Comparative Reevaluation

Heiss¹,

Graf²,

Wienhard³

2001

Cerebrovasc Dis

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Repeat studies in animal models of acute focal ischemia can be compared to incidental studies in the course of ischemic stroke in order to shed light on the development of changes causing ischemic infarcts or recovery of critically perfused tissue. Positron emission tomography (PET) studies of regional cerebral blood flow, cerebral metabolic rate for oxygen, oxygen extraction fraction (OEF), cerebral metabolic rate of glucose and flumazenil (FMZ) binding in the cat middle cerebral artery occlusion (MCAO) model and in patients with acute ischemic hemispheric stroke were reviewed. After permanent MCAO, the development of ‘misery-perfused’ penumbral tissue and its centrifugal conversion into necrosis could be demonstrated, resembling focal pathophysiological changes in patients with ischemic attacks. In the experimental model and in vascular insults in humans, a chance of recovery existed if collateral perfusion developed spontaneously within the first hours. In transient MCAO, reperfusion was only effective 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 the other instances when oxygen metabolism broke down, and an increased OEF was no longer seen, reperfusion even at levels above preocclusion had no effect, and large space-occupying infarcts developed. These experimental findings are comparable to the variable outcome after thrombolytic therapy; if reperfusion is achieved within the therapeutic window of tissue viability, large infarcts are prevented and complete or partial recovery can be achieved. In the experimental model of focal ischemia and in human stroke, FMZ can be utilized as a marker of neuronal integrity. If FMZ binding in the cortex is decreased below 4 times the mean value of white matter in the acute stage, permanent infarcts were observed on late CT/MRI; this irreversible damage could not be prevented by thrombolytic therapy. These results demonstrated that PET studies in suitable ischemia models in cats can help to explain various courses and diverging outcomes of acute ischemic stroke. Comparable findings from experimental ischemia and human stroke may affect the selection of appropriate therapeutic strategies.

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Positron Emission Tomographic Measurement of Acute Hemodynamic Changes in Primate Middle Cerebral Artery Occlusion

Cited by 16 publications

References 2 publications

Relationships between High Oxygen Extraction Fraction in the Acute Stage and Final Infarction in Reversible Middle Cerebral Artery Occlusion: An Investigation in Anesthetized Baboons with Positron Emission Tomography

Relationships between High Oxygen Extraction Fraction in the Acute Stage and Final Infarction in Reversible Middle Cerebral Artery Occlusion: An Investigation in Anesthetized Baboons with Positron Emission Tomography

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

Relevance of Experimental Ischemia in Cats for Stroke Management: A Comparative Reevaluation

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