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The Protection Of Ischemic Myocardium By Intravenous Infusion Of Drag-reducing Polymers

Posted on:2012-01-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:K CuiFull Text:PDF
GTID:1114330368475480Subject:Internal Medicine
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Background & ObjectiveIt is shown to us, that the blood-soluble drag reducing polymers(DRPs) can decrease the resistance of the blood flow in vascular, increase the perfusion and tissue oxygenation, when injected in blood at minute concentration in vitro model or vivo animal model of normal or restricted blood flow model. Rencent studies had proved the survival time of rat with acute myocardial infarction can be prolonged by the injection of PEO solution, and the blood flow of ischemic myocardium is improved by the miracle solution. So we hypothesis that the DRPs may improve left ventricular (LV) function in rats with surgically induced MI, furthermore DRPs may have the potential therapeutic effect in treating tissue hypoperfusion caused by atherosclerosis cardiovascular disease (ACVD) or diabetes such as coronary heart disease,shock and peripheral arterial disease. Our study is mean to test the protection on ischemic or acute infracted myocardium of DRPs, and try to find out some conceivable mechanisms of the observed DRPs effects on blood flow, and it is necessary for the process of becoming the chemical into a medicine. MethodsIn our series of test, we characterize and assess efficacy of DRPs for possible usage in atherosclerosis cardiovascular disease (ACVD). The first thing is to make sure that our solution can reduce the restriction of flow in vitro.0.2g commercial polyethylene oxide (PEO) with an average molecule weight of 5×106 Dalton was weighting using a precision balance, Put the PEO powder into a beaker with careful, dissolved with 100ml normal saline, then dialyzed against normal saline to exorcize the low molecule weight and impurities. A hydrodynamic system,which was made of a pump,a thin glass tubing, was developed, two sensor beside the tubing was to measure the driving pressure of flow in the microtubing, was made to test the resistant of NS or red cell suspension containing nano-molarity of PEO.A rat model of LAD ligation induced MI, were used to find out if the rat heart function as LVEF (left ventricle ejection fraction),wall motion score index and contrast score index etc were reserved by the injection of PEO.Latter, the effect on microvascular were examed on a normal dog model, Finally, we test the drag-reducing efficacy of PEO and how much the PEO can ameliorate the volume and speed of the blood flow in microvascular in the dog model of restrict blood flow of LAD. Based on the dp measured at the situation normal without stenosis,normal +AD(adenosine) stress without stenosis,stenosis,stenosis+ AD stress,stenosis+PEO and stenosis +PEO+AD stress, each condition we made MCE(myocardial contrast echocardiography) and record the pressure before and after the stenosis part of the artificial blood vessel under the maximum hyperemia of the myocardium, so we can see if it can improve the FFRThe MCE clips were analysised in iMCE software, the data as plateau video intensity (A) and the refilling velocityof contrast(β) etc. were compared using Analysis of variance of repeated measure data.ResultThe addiction of PEO to vitro circulating system produced a markable reduction in the pressure drop required to achieve a particular flow rate, or at a fixed flow rate,the driving pressure is lower significant than the situation while the PEO is absent; suggesting a drag reduction effect of PEOs with 5×106 MW.24h following MI, the morbility was significantly different among the sham, MI and DRP groups (P= 0.023), and the LVEF,Wall motion score index and contrast score index were significantly better in DRP group compared with that in NS group (both P<0.001). Comparison using pair t-test between two measurements showed no systematic error (all P>0.05).Viscosity data revealed that at the concentration of 2.5 ppm in our study, DRP had no effect on blood viscosity.In normal dog model, transthorax MCE shown:with the injection of PEO or adenosine or both,the plateau video intensity (A, represent the capacity of capillaries bed) and the refilling velocityof contrast(β, demonstrate the flow speed of capillaries bed) were significantly improved compared with normal condition.Compare with the normal LAD, the dog model of restrict blood flow of LAD under the adenosine(AD) stress,single stenosis,stenosis with AD stress,stenosis with PEO injection and stenosis with AD stress and PEO injection, the FFR,blood flow measured by ultrasonic flowmeter,plateau video intensity(A),refilling velocity of contrast(β),flow rate of myocardial capillary vessel bed (A×β)and heart beat counts of delayed MCE visualization of the ischemic part of myocardium get a significant improve.ConclusionAcute administration of DRPs improved LV function in a rat model of MI possibly by improving microvascular blood flow due to their unique hydrodynamic properties, in dog model,we also proved that DRPs can improve blood flow both normal myocardium and ischemic myocardium. DRPs may offer a novel approach to the treatment of coronary artery ischemic diseases or atherosclerosis cardiovascular disease.
Keywords/Search Tags:Drag-reducing polymers, Myocardial contrast echocardiography, Left ventricular function, Fractional flow reserve
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