GRADED HYPOTENSION AND MCA OCCLUSION DURATION - EFFECT IN TRANSIENT FOCAL ISCHEMIA

The first 2 h of middle cerebral artery occlusion (MCAO) are likely cr itical in determining the final outcome in ischemic stroke. To study t his early postischemic period, male Wistar rats (n = 161) were subject ed to right MCAO with closely spaced step variations in both duration of MCAO and blood pressure (BP), using the intraluminal suture techniq ue. Quantitative neuropathology was performed at 25 coronal planes of the brain after 1-week survival. Atrophy was measured as the differenc e between the two hemispheres and was added to cortical and striatal n ecrosis to obtain total tissue loss. Damage consistently increased mon otonically with increasing duration of occlusion only when infarct siz e was expressed as percentage of the contralateral hemisphere, but not when expressed as mm(3), because of variable tissue size. The results showed that already at 1 week, the quantity of tissue loss due to res orption and transsynaptic effects approached the quantity of geographi cally traceable necrosis in cortex and striatum. Minimum brain damage (5%) occurred after 60 min at a BP of 80 mm Hg, with almost no cortica l necrosis. Damage was extremely sensitive to hypotension and MCAO dur ation. At a BP of 40 mm Hg, 60 min of MCAO produced 25% damage, accele rating every 20 min during the 2-h period studied. At BP 80 mm Hg, 120 min of MCAO produced the same damage as only 80 min of MCAO at BP 60 mm Hg. At 60-, 80-, 100-, and 120-min duration of MCAO, infarct size w as significantly reduced with increasing BP. Analysis of the independe nt contribution of BP and MCAO duration revealed that BP played a grea ter role in determining infarct size than did MCAO duration. Ipsilater al hippocampal damage was seen in CA1 and, in some animals, CA3. Necro tic neurons in hippocampus were found in 21 animals, including four wi th bilateral hippocampal damage, largely but not exclusively distribut ed in the hypotensive groups. Contralateral necrotizing damage was see n in cortex and hippocampus as selective neuronal necrosis and as cort ical infarction in two animals. Ipsilateral and contralateral hippocam pal damage reproduced the pattern of selective vulnerability seen in g lobal ischemia. The histologic penumbra (rim of selective neuronal nec rosis surrounding the infarct) increased over time at BP 80 mm Hg but remained constant at a larger, presumably maximal level at BP 40 mm Hg in spite of increasing infarct size. We conclude that the first 2 h a fter MCAO is a very dynamic period, with increasing infarct size every 20 min, a process extremely sensitive to hypotension during occlusion . Transsynaptic effects can produce necrotizing damage in the hemisphe re opposite to the ischemia.