| Objective: Thrombolysis via vein is nowadays a common medical method for thrombus therapy.However,the results of the method are influenced by the thrombus formation time and the medicine dose.How to enhance the thrombolysis results is an urgent problem.Ultrasonography and microbubble contrast agent have been a new method for the treatment of every kind of acute and chronicity thrombus and have a promising application perspective.On the one hand,ultrasound is not only applied in diagnosis,its therapeutical effect also attracts more attentions with the development of researches on the bioeffect of ultrasound.On the other hand,with the development of the microbubble contrast agent,which greatly increases the efficiency of ultrasonography,the ultrasonic therapy is improved to a higher level.Researches in the past mostly focus on the acute thrombus,the chronicity thrombus is seldom studied.However,many thrombotic patients have passed the acute period clinically,the curative effect of chronicity thrombus needs investigation urgently.Thrombus is an intermediate structure between solid and liquid.There are different curative effects for different thrombus.Acute thrombus is not stable and thus has a good curative result while chronicity thrombus is relatively stable,and has a bad curative effect.At present,it is clinically urgent to analyze comparatively the curative effects of the thrombus with different formation time,find the optimum therapy period,and reasonably use medicine,so that the medicine dose and complication are decreased.The common therapy methods used in clinic are systematic thrombolysis and catheter directed thrombolysis.The catheter directed thrombolysis is a new wiresoft vessel treatment technique.Compared with the periphery thrombolysis,catheter directed thrombolysis increases the curative efficiency,reduces the medicine dose,and avoids the risks of hemorrhage complication.At the meantime,catheter directed thrombolysis also avoids the wound due to surgical sectioning and the disunion of the wound,the complication of lymphatic fistula.In short,the catheter directed thrombolysis has been the most common therapy method for thrombus at present.The virtual touch tissue quantification(VTQ)is a new technique which is used to evaluate non-invasively the tissue elasticity.It can be used for the quantitative analysis of thrombus elasticity.VTQ solves the integrated boundary condition problems of elastic reconstruction of biological tissues,lowers the complexity of tissue elastic reconstruction,and approximately unifies the elastic reconstruction method of different biological tissues.VTQ can be used to estimate the hardness and the formation time of thrombus.Methods: 1.Vine blood,each 1.0ml,sampled from one hundred health volunteers,contained in centrifuge tubes with volume of 5ml,was divided into five groups and was placed in water bath box for 1,3,7,14 and 21 days after the thrombus formation.The initial weights after different formation time were weighed.Each group of different formation time was divided into four subgroups and was treated by urokinase,urokinase and ultrasound,urokinase and microbubble.The last subgroup acted as control group.After the different treatment,the residual weights of the thrombus were weighed,the thrombolysis rates were calculated,the pathology of thrombus after thrombolysis was analyzed,and correlation analysis between the thrombus formation time and thrombolysis rate was conducted.2.Forty five animal models with thrombus were prepared from grown health hybrid dogs.One femoral vein was ligated,between the near end and the far end,to form a 4cm length ligation,into which 100 units thrombin diluted with 5ml normal saline was injected.The formation of thrombus was affirmed by ultrasound and X ray angiogram.The experimental dogs were divided into five groups according to the thrombus formation time,which correspond respectively to 1,3,7,14,and 21 days.Each groups were again divided into four subgroups and treated by urokinase,urokinase and ultrasound,urokinase and microbubble.The last subgroup acted as control group.After the treatment,the thrombolysis effects were evaluated and the pathology analysis of the thrombus vessels was carried out.3.Thirty patients received between Mar.2011 and Feb.2012 were diagnosed as lower extremity deep vine thrombosis,by clinic features,physical sign examination and color Doppler examination.Among which,9 patients have thrombosis formed within 3 days,14 patients between 4 days and 4 weeks,and 7 patients with thrombosis exceeding 4 weeks.The VTQ values were measured at the depths less than or equal to 3cm and greater than 3cm,and the correlation analysis was conducted for different thrombus formation time.Results: 1.In general,the thrombolysis rate of vitro thrombosis with any formation time is ranked from low to high as control group,urokinase group,urokinase and microbubble group,and urokinase and ultrasound group.The best curative effect is obtained in the urokinase and ultrasound group.In the respect of thrombus formation time,thrombosis within 7 days has a good thrombolysis effect,and the thrombolysis rate is about 50%.If the formation time exceeds 7 days,the thrombolysis effect is poor.The thrombolysis rates for the thrombosis of 14 days and 21 days are only 30% or below.Different formation time and thrombolysis methods have different thrombolysis rates.There exists negative correlation between the thrombus age and thrombolysis rate.The correlation coefficients are respectively-0.769,-0.706,-0.800 and-0.231 for the urokinase,urokinase plus ultrasound,urokinase plus microbubble,and control groups.The micro structure of the untreated thrombus is characterized as uniform distribution of thrombosis red blood cells and dense fiber frame.After ultrasonic irradiation,there are cracks and vacuolus in the thrombus.The peripheral fiber frames get loosened,the distance between red blood cells increase and the internal structure of thrombosis is destroyed.2.As shown by color Doppler and X ray angiogram,there is blood flow in the thrombosis vessels after treatment.Different formation time and different therapy correspond with different blood flow recanalization classification.For the 1 day thrombosis,the recanalization classifications of urokinase,urokinase plus ultrasound,and urokinase plus microbubble groups are all 100%.With the increasing of the formation time,the recanalization classifications of urokinase,urokinase plus ultrasound,and urokinase plus microbubble groups all increase from I class to IV class gradually.The thrombus formation time of different treatment group has positive correlation with recanalization classification,and the correlation coefficients are 0.939 for urokinase group,0.949 for urokinase plus ultrasound and urokinase plus microbubble groups.As for the thrombosis ages,the recanalization classification of 1 day thrombus treated by urokinase,urokinase plus ultrasound,and urokinase plus microbubble are same,and comparing with the control group gives P=0.025.P=0.003 and 0.001 correspond respectively to the recanalization classifications of 3 days thrombosis treated by urokinase and urokinase plus ultrasound and plus microbubble,compared with the control group.P=0.013 and P=0.005 correspond to the of 7 days thrombosis.P=0.264 and P=1 correspond to the of 14 days and 21 days thrombosis.3.The VTQ values of thrombosis with formation time equal to or less than 3 days are lager than that of 4 days to 2 weeks thrombosis(the second group)or the above 2 weeks thrombosis(the third group).In the respect of VTQ for different depths,there is no obvious difference between the VTQs in the depth less than 3cm and that in average depth in the first group.There is no obvious difference between the VTQs of different depths in the second and the third groups.With the increase of the formation time,VTQ value decreases,and a negative correlation exists between them.The correlation coefficients are respectively 0.53 for depth of 3cm,0.38 for depth larger than 3cm,and 0.56 for the average depth.Conclusions: 1.The treatment of urokinase plus ultrasound can remarkably increase the thrombolysis rate for the vitro thrombus,and is superior to that of urokinase plus microbubble.2.The treatment of urokinase plus ultrasound and microbubble has a certain thrombolysis effects.The urokinase,ultrasound and microbubble can act cooperatively,as the result,the dose of urokinase is reduced and the risk of complication of thrombolysis is lowered.This method has a broad application perspective.3.The acute thrombus has a good thrombolysis effect and the chronic one has a poor effect.The thrombolysis effect for the thrombosis with formation time equal to or longer than 21 days is not so good,besides,the risk of complication increases.4.The virtual touch tissue quantification technique can precisely measures the thrombosis elasticity,and indirectly estimate the hardness of thrombus.5.With the increase of the thrombus formation time,the elasticity of thrombus decreases,and the hardness increases.The elasticity at different depth is different,therefore,multiple measurements should be carried out at different depth and the average value should be used to represent the elasticity. |
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