Study Of The Effect Of Microembolization On Tissue Reperfusion And Its Therapeutic Interventions

Objectives To (1)develop an experimental animal thrombolysis model to evaluate not only the recanalization of thrombosed large vessels, but also the microcirculatory consequence of downstream tissue; (2) examine the microembolization during thrombolytic therapy and correlated tissue perfusion diminution; and (3)explore some adjuvant interventions combined with common thrombolysis to improve the microcirculatory condition.Methods Taken the Cremaster Arteries as target vessel, 56 male SD rats(200 10g) were randomly assigned to 4 groups: (1) group 1 (thrombolysis group, n=14): Thrombosis was induced photochemically in cremaster arteries by injecting hematoporphyrin (1mg/kg) and then exposing the target vessels to ultraviolet light (455 m). After 10 minutes of occlusion, the animals received recombinant staphylokinase (r-SAK, 1mg/kg. 2/3 bolus injection followed by 1/3 infusion over 30 minutes). After recanalization, saline was infused over 2 hours. (2) group 2(autolysis group, n=9): After thrombosis and occlusion of target vessels, the animals were given saline without thrombolytic agents so as to contrast the thrombolytic effect of r-SAK with group 1. (3) group 3(clamping and releasing group, n=9): In this group, vessel block were made by clamping with micro serrefine. After 30 minutes of ischemia, the target vessel was release. With this method, a different ischemia-reperfusion pattern comparing with group 1 was made in order to contrast the exchanges of tissue perfusion. (4)group 4(adjuvant intervention group, n=24): With the save method as group 1 to inducethrombosis and vessel occlusion, the animals accepted some adjuvant interventions after recanalization. This group was randomly assigned to 3 subgroups according the different adjuvant interventions: (i) heparin group, (ii) low molecular dextran group and (iii) continuous thrombolysis group (given additional r-SAK (1mg/kg) over 2 hours). The process of the clot lysis in large vessels and the circulatory conditions in microvasculars were recorded through vital microscope equipped with video recording system, the lytic and microcirculatory parameters, such as degree of recanalization (DR), microvessel flow velocity (MFV), time to lysis (TL) and formation of microemboli, were measured by computerised image analysis, and the terminal tissue blood flow (TBF) were assayed with Laser Doppler Perfusion Imager.Results (1) There were no significant difference of lysis rate and DR (P>0.05) between group 1 and group 2, but TL decreased in group 1 and reached statistical significance (P<0.05). (2)After recanalization, the TBF values in group 1 were statistically lower than that before thrombosis (P<0.05), and it were also statistically lower than the corresponding values in group 3 (P<0.05), which had no statistical changes compare with that before clamping (P>0.20). Moreover, microemboli can be found widespread in microvessels and capillaries in group 1, whereas they were hardly found in group 3. (3)Oneway analysis of variance revealed that the improvement of TBF among group 1 and subgroups of group 4 was significantly different (P>F=0.0086), and the continuous thrombolysis group had a statistically significant effect on TBF improvement (P=0.014), whereas the other groups hadn't. However, even in continuous thrombolysis group, the TBF can't be recovered to the level before thrombosis.Conclusions With the newly established rat cremaster arterythrombosis model, both the recanalization of thrombosed large vessels and the microcirculatory consequence of downstream tissue can be evaluated simultaneously. Microembolism indused during thrombolytic therapy has close correlation to the microcirculation disturbance after recanalization of the target vessel. Extending the time and dosage of thrombolytic agent infused following bolus injection can partly improve the circulatory condition.