Thresholds in cerebral ischemia - the ischemic penumbra.

COMPLETE ARREST of the cerebral circulation leads within seconds to cessation of neuronal electrical activity and within a few minutes to deterioration of the energy state and ion homeostasis. Depletion of high energy phosphates, membrane ion pump failure, efflux of cellular potassium, influx of sodium, chloride and water, and membrane depolarization occur swiftly. If such chaos persists for longer than 5-10 minutes, irreversible cell damage is likely. Such is the inevitable sequence of events if blood flow to the brain is arrested. If, however, the ischemia is incomplete the outcome is more difficult to predict and is largely dependent on residual perfusion and oxygen availability. It is in large measure the outcome of incomplete cerebral ischemia, which is of particular interest in cerebrovascular disease. With occlusion of a cere-bral vessel and signs of acute stroke, ischemia is hardly ever total. Some residual perfusion persists in the ischemic area dependent on collateral vessels and local perfusion pressures. Recent evidence indicates that immediate failure of basic functions such as synaptic transmission, ion pumping and energy metabolism in the ischemic brain, is critically dependent on residual blood flow, and that these functions fail at certain critical flow thresholds. It appears, further, that the development of infarction is critically correlated to residual per-fusion, and there is a lethal threshold of residual blood flow below which tissue infarction develops after a certain time. Such knowledge provides the theoretical background for application of the instrumentation now being developed for repeated non-invasive 3-dimensional imaging of residual flow in the ischemic brain. By these means one hopes it will become possible to conduct treatment and to evaluate prognosis in the acute stroke patient by reproducible repeatable measurement in man. In man, flattening of the EEG occurs immediately if hemispheric flow falls below 0.16-0.17 ml-g^min 1 as evidenced by measurements of cerebral blood flow and EEG during clamping of one carotid artery in end-arterectomy. 1-* The critical relationship between cere-bral electrical activity and blood flow which such clinical observation suggested has been amply proven in exDerimental studies. Svmon and Branston and co-workers' demonstrated that the evoked somato-sensory potential recorded in baboon cortex was abolished at local flows below about 0.15 ml'gr^mirr 1. This flow level could be regarded as critical in the sense that electrical function in the cortex was abolished below but sustained above this level. It has, therefore, been referred to as the flow threshold of electrical …