TEMPORAL IMPAIRMENT OF MICROCIRCULATORY PERFUSION FOLLOWING FOCAL CEREBRAL-ISCHEMIA IN THE SPONTANEOUSLY HYPERTENSIVE RAT

Microcirculatory impairments have theoretically been proposed as a pot ential factor in the development of ischemic injury, but few attempts have been made to directly assess microvascular patency following stro ke. To address this issue we investigated the temporal changes in micr ovascular perfusion induced by permanent focal ischemia. Halothane-ane sthetized spontaneously hypertensive rats were subjected to middle cer ebral artery occlusion (MCAO) of 5 min to 4 h duration. Two fluorescen t tracers (FITC-dextran and Evans blue) were then sequentially adminis tered i.v. and allowed to circulate for 10 and 5 s respectively. Tissu e sections were examined by fluorescent microscopy, and the mean numbe r of perfused microvessels/mm(2) calculated for cortical areas represe nting non-ischemic (Region A), perifocal/penumbral (Region B) and core ischemic (Region C) regions. For sham-operated controls, virtually al l microvessels perfused with tracer within 5 s. In contrast MCAO induc ed significant reductions in the number of perfused microvessels in Re gions B and C. The most marked impairments in perfusion were observed in core MCA territory (e.g. 2-10% of control values for 5 s circulatio n period) while, initially, the deficit was less severe in penumbral c ortex. However, a secondary perfusion impairment developed over time i n the perifocal/penumbral region, so that the deficit was greater 4 h after MCAO than at earlier time points (e.g. 72%, 71% and 22% of contr ol value for 0.5, 1 and 4 h MCAO respectively; 10 s circulation period ). In conclusion, MCAO induced severe impairments in microcirculatory perfusion within the core ischemic region, and to a lesser extent in t he penumbra. However, the development of a more severe perfusion defic it in the penumbra within 4 h of MCAO supports the hypothesis that mic rocirculatory failure in this region contributes to its recruitment to the ischemic infarct. (C) 1997 Elsevier Science B.V.