Evolution of microcirculatory disturbances after permanent middle cerebralartery occlusion in rats

Nonischemic brain capillaries show a continuous and heterogeneous plasma pe rfusion. In the current study, plasma perfusion was investigated in rats du ring 2 to 168 hours of permanent middle cerebral artery occlusion. Perfused capillaries were detected in brain cryosections by fluorescein isothyocana te (FITC) dextran after 10 minutes of circulation time. Heterogeneity of ca pillary perfusion was identified by Evans blue (EB), which circulated for 3 seconds. In this setting, the heterogeneity of intracapillary EB concentra tions reflects heterogeneities in capillary flow velocities. The CBF was qu antified by simultaneous iodo[C-14]antipyrine autoradiography. When moving from normal flow to low-flow areas in the ischemic hemisphere, three states of capillary filling could be distinguished: state 1-fast perfusion, filli ng by FITC dextran and EB (CBF 0.33 mL . g(-1) . min(-1)); state 2 -delayed perfusion, only FITC dextran filling (CBF 0.104 mt g(-1) min(-1)); state 3 -minimal perfusion, no dye filling (CBF 0.056 mL . g(-1) . min(-1)). In tis sue of state 1 at the borderline to ischemic tissue, a higher heterogeneity of intracapillary EB concentration (85.7%) was found than in the contralat eral nonischemic hemisphere (76.4%) (P < 0.05), indicating a compromised mi crocirculation. The adjacent ischemic areas were filled by FITC dextran (st ate 2) 2 to 4 hours after middle cerebral artery occlusion, indicating a ma intained, although slow, perfusion at this time. Later, minimal perfused ar eas (state 3) progressively replaced the delayed perfused areas (state 2). This study shows, for the first time, the evolution of microvascular distur bances in relation to CBF. In the low-flow areas, an early residual plasma perfusion is later followed by a lack of perfusion or minimal perfusion. In areas of higher, although reduced flow at the border between normal and is chemic tissue, an extreme capillary perfusion heterogeneity indicates perma nent microcirculatory abnormalities.