STABLE PROSTACYCLIN IMPROVES POSTISCHEMIC MICROCIRCULATORY CHANGES INHYPERTENSIVE RATS

The prostacyclin analogue TTC-909 is incorporated in lipid microsphere s and is chemically very stable. We examined the efficacy of TTC-909 o n cerebral microcirculation following focal cerebral ischaemia. Focal cerebral ischaemia was produced by the occlusion of the distal middle cerebral artery in stroke-prone spontaneously hypertensive rats. Intra venous administration of TTC-909 (100 ng/kg/day) or vehicle was starte d 30 minutes after the occlusion and repeated for 7 days. On day 7, ce rebral blood flow and blood-brain barrier permeability were measured a utoradiographically. Brain oedema was estimated by the gravimetric met hod. The size of the infarction was calculated from area measurements on serial histologic sections. Treatment with TTC-909 resulted in sign ificant improvement in regional blood flow in the ischaemic rim (p<0.0 1) and the surrounding area (p < 0.05). With TTC-909 treatment, the in creased permeability was significantly reduced in the ischaemic centre (p < 0.01) and rim (p < 0.05). A decrease in specific gravity in the ischaemic region and the remote non-ischaemic regions was prevented by the treament (p < 0.01). We assumed that the efficacy of TTC-909 main tains the blood supply in the ischaemic area, improves disruption of t he blood-brain barrier and prevents development of ischaemic oedema.