| Objectives: â‘ To establish a new canine model of focal cerebral infarction that be suit for the study of imaging diagnosis and thrombolytic therapy, and to evaluate the technique feasibility and stability; â‘¡ To study the effect and complications of r-Sak for acute cerebral infarction thrombolysis with different doses in canine mode, and compared with UK, and then to evaluate the fit dose, the safety and the efficacy of intraarterial r-Sak ; â‘¢To observe the effect of r-Sak on plasma levels of coagulation and thrombolytic parameters in canine. Methods: â‘ Six beagle dogs were selected into the study. The white thrombus was coagulated with dog's self-venous blood. The 4F headhounter catheter was inserted into the left internal carotid artery and the thrombi was injected under fluoroscopic guidance. The cerebral angiography was performed before and after the embolization. The patency of the occluded cerebral arteries were examined by angiography at 1, 2 and 5h after the embolization. These dogs were sacrificed and the cerebrum was taken out for pathology study at 24h; â‘¡The embolism model of acute cerebral infarction was established with interventional technique in 30 adult beagle dogs, which were randomly divided intocontrol(saline, 10ml), r-Sak low dose(r-Sak, 5,000U/kg), r-Sak middle dose(r-Sak, 10,000U/kg), r-Sak high dose(r-Sak, 20,000U/kg)and UK(UK, 10,000U/kg) groups. Angiography and intraarterial thrombolysis within 30 minutes were performed 5 hours after embolization, and angiography was repeated half, 1 and 2 hours after thrombolysis to observe recanalization. Blood samples were collected at a series of time pre- and post-thrombolysis to examine the plasma levels of PT, APTT and D-dimer. These canines were sacrificed, and their cerebri and vessels were taken out for pathologic study at 24 hours.Results: ?The middle cerebral artery occlusion occurred in all 6 dogs, 4 of which had other cerebral artery occlusion. All occluded arteries were not patent at 2h after embolization, but 1 posterior communicating artery was partly patent at 5h. All dogs were survived at 24h without any severe complications. The cerebral infarctions were found in dog's deep cerebrum; (D The rate of efficacy in 2 hours after thrombolysis was 10.0% (1/10) in control group, 40.0% (4/10) in low dose group, 90.9% (10/11) in middle dose group, 100% (9/9)in high dose group and 33.3% (3/9) in UK group, respectively. There statistically are obvious differences among groups(p<0.05). The rate of complete recanalization was 0(0/10), 10% (1/10), 36.4% (4/11), 66.7% (6/9), 0(0/9), respectively. There are also statistically obvious differences among groups (p<0.05); (DThe death occurred in 1 canine of high dose group whin 24 hours afterthrombolysis, the others were survived. The hemorrhage was found in puncture point with 6, 2 dogs respectively of the high dose and middle dose group after thrombolysis. There were better clinical results in r-Sak intraarterial group. The hemorrhagical lesion in parietal lobe of brain was found in 1 canine of r-Sak high dose group. There were still small partial cerebral infarctions in light microscopy of r-Sak middle dose group after occlusived artery complete recanlization. Other groups were all found cerebral infarctions in brain. â‘£ The PT markedly prolonged in UK group(P<0.05) and all r-Sak groups(P<0.001) after thrombolysis, and there also are significantly obvious difference between UK and r-Sak low dose group(P<0.01). The APTT prolonged significantly in all r-Sak groups(P<0.001). There were no obvious changes in all groups pre- and post-thrombolysis(P=0.884).Conclusions: â‘ The model of acute cerebral infarction in dogs with interventional embolism is simple microinvasive and reliable. The method does serve as a useful model for the early medical imaging diagnosis and thrombolytic therapy of acute infarction; â‘¡Obvious recanalization was shown after intraarterial thrombolysis with r-Sak within 5 hours after onset of thrombosis. There is relative high rate of recanalization with no less than 10,000U/kg of r-Sak but acompanied with high risk of hemorrhage following dose increase. Therefore, 10,000U/kg of r-Sak is fit dose for intraarterial thrombolysis; â‘¢On the...
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