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We examined the consequences of reflow on metabolic recovery following increasing periods of focal ischemia. The middle cerebral artery of 21 Sprague-Dawley rats was occluded with a snare ligature for 1, 2, or 6 hours followed by 5, 4, or 0 hours of reflow, respectively (seven rats in each group). All animals were injected with neutral red for visual confirmation that the affected regions were reperfused. The brains were frozen in situ, and the concentrations of adenosine triphosphate, phosphocreatine, glycogen, and lactate were determined in those areas corresponding to the normally perfused medial ipsilateral cortex, the perifocal region, and the ischemic focus. Values for the 6 hours' occlusion with no reflow group served as a control to demonstrate restoration of metabolite concentrations. In both groups with reflow, the levels of high-energy phosphates were greater than control, but this effect of reflow was primarily significant for the group with 1 hour's occlusion (p less than 0.05). The levels of glycogen and lactate provided additional evidence that the extent of metabolite restoration was graded; following 2 hours of occlusion, metabolite recovery was compromised (p less than 0.05). Our data strongly support the concept that the window of opportunity for effective treatment of focal ischemia by reperfusion is narrow (of short duration).

Impairment of metabolic recovery with increasing periods of middle cerebral artery occlusion in rats.