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Titolo:
Perfusion thresholds in human cerebral ischemia: Historical perspective and therapeutic implications
Autore:
Baron, JC;
Indirizzi:
Univ Caen, INSERM U320, F-14074 Caen, France Univ Caen Caen France F-14074 iv Caen, INSERM U320, F-14074 Caen, France
Titolo Testata:
CEREBROVASCULAR DISEASES
, volume: 11, anno: 2001, supplemento:, 1
pagine: 2 - 8
SICI:
1015-9770(2001)11:<2:PTIHCI>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON-EMISSION-TOMOGRAPHY; BLOOD-FLOW; ACUTE STROKE; CAROTID ENDARTERECTOMY; ARTERY OCCLUSION; BRAIN INFARCTS; CELL-DENSITY; BORDER ZONE; PENUMBRA; TISSUE;
Keywords:
PET; SPECT; penumbra; cerebral blood flow; brain infarction; positron tomography;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Baron, JC Univ Caen, INSERM U320, POB 5229, F-14074 Caen, France Univ CaenPOB 5229 Caen France F-14074 29, F-14074 Caen, France
Citazione:
J.C. Baron, "Perfusion thresholds in human cerebral ischemia: Historical perspective and therapeutic implications", CEREB DIS, 11, 2001, pp. 2-8

Abstract

After middle cerebral artery occlusion (MCAO) in the laboratory animal, the ischemic penumbra has been documented as a severely hypoperfused, functionally impaired, but still viable cortex which can regain its function and escape infarction if it is reperfused before a certain time has elapsed. Thepenumbra surrounds the ischemic core of already irreversibly damaged tissue, and is progressively recruited into the core with increasing MCAO duration. In the animal, the threshold of cerebral blood flow (CBF) below which neuronal function is impaired and the tissue is at risk of infarction is around 22 ml/100 g/m in ( similar to 40% of normal) in the awake or lightly anesthetized monkey, and around 30-35 ml/100 g/m in in the cat and the rat. The threshold of CBF below which the tissue becomes irreversibly damaged andwill progress to infarction depends on the duration of ischemia, and is around 10 ml/100 g/min for 1-2 h ( similar to 20% of normal) and around 18 ml/100 g/min for permanent ischemia in the monkey. Mildly reduced CBF down tothe 40% threshold (termed 'oligemia') is normally well tolerated, and the affected tissue is not at risk of infarction under uncomplicated conditionstin the animal, however, selective neuronal death may occur even with onlymildly reduced CBF values, but this sequela of stroke seems an exceptionalencounter in man). Classic studies with carotid artery clamping in man have provided estimates for the penumbra threshold at around 20 ml/ 100 g/min for the whole brain, but only recently have imaging studies allowed to document the existence of the penumbra in acute stroke and given estimates of local CBF thresholds. With PET, the penumbra is characterized by a reduced CBF, an increased oxygen extraction fraction, and a relatively preserved oxygen consumption (CMRO2). In a series of PET studies performed 5-18 h after stroke onset, we have determined the threshold for penumbra to be around 20ml/100 g/min, and documented that the extent of neurological recovery is proportional to the volume of penumbra that eventually escaped infarction. Within this time interval, the thresholds for irreversible damage were around 8 ml/ 100 g/min for CBF and around 0.9 ml/100 g/min for CMRO2. Recent studies with diffusion-weighted and perfusion MR have reported similar relative thresholds for CBF of about 50 and 18% for penumbra and core, respectively. Although it is likely that the threshold for irreversibility will be lower with shorter duration since clinical onset, this has not been documentedthus far. Because saving the penumbra will improve clinical outcome, it should constitute the main target of acute stroke therapy. We found evidence of penumbra in about one third of the cases studied between 5 and 18 h after onset, and as late as 16 h after symptom onset in occasional patients, suggesting the therapeutic window may be protracted in at least a fraction ofthe cases; similar experience has recently accrued from diffusion-weightedMR and perfusion MR. In the remaining patients, there was evidence of early extensive damage or early spontaneous reperfusion, which would make them inappropriate candidates for neuroprotective therapy. Recent evidence from PET studies of relative perfusion performed within 3 h of onset suggests that early thrombolysis indeed saves the tissue with CBF below a critical threshold of 12 ml/100 g/min, with a correlation between the volume of such tissue escaping infarction and subsequent neurological recovery. Thus, mapping the penumbra in the individual patient with physiologic imaging should allow to formulate a pathophysiological diagnosis, and in turn to design a rational management of the stroke patient and to increase the sensitivity of drug trials by appropriate patient selection. Copyright (C) 2001 S. Karger AG, Basel.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/06/19 alle ore 17:45:04