Experimental study on the reversibility of cerebral ischemia. Residual blood flow and duration of ischemia.

The flow threshold and time threshold for reversibility of cerebral ischemia were studied using a canine model of cerebral ischemia regulated by controlled perfusion of cerebral blood flow (CBF). CBF was continuously monitored with a laser Doppler flow meter, the brain was brought to a constant level of ischemia for a defined period of time, after which recirculation was instituted. The electroencephalogram (EEG) and somatosensory evoked potentials (SEP) were monitored and used as an index of brain function. No recovery of brain function was found following recirculation if the CBF was reduced to a level below 20% of the normal state for more than one hour. When residual blood flow was 30% of the normal level, however, recirculation after one hour of ischemia resulted in nearly complete recovery of brain function. Significant functional recovery was not seen after two or more hours of such ischemia. Nearly complete recovery was also seen following reperfusion within three hours with 40% of normal CBF. It was demonstrated that the reversibility in the ischemic brain was critically correlated to the level of blood flow and its duration. If these results can be applied to the human brain, emergency cerebral revascularization for ischemic stroke should be attempted when critical flow and time thresholds have not been crossed, namely, in less than 1 hour and 3 hours of insult when the residual blood flow is reduced to 30 and 40% of the normal state, respectively. In clinical situations, this "critical time" may be too short for acute revascularization unless cerebral protective measures are applied pre-operatively to prolong the viability period of ischemic cerebral tissue.