| Background and Objective :The study of MRI has always been a hot topic of basal and clinical medicine research since it can affect many fields such as treatment of coronary heart disease and myocardial infarction and heart protect during heart operations.In recent years,more and more attention has been paid to the relationship between RAS,especially AngⅡand MRI. AngⅡincluding that in local cardiac muscle after ischemia is thought to intensify MRI。We observed AngⅡ's influence during rabbit's MRI and losartan's protection towards damaged myocardial muscle.Methods:1. animal experiment(1) Set up rabbit model of MRI with Simpson method and test the result with ECG and color change of cardial muscle.(2) Inspect LVSP,LVDP,the greatest speed of systole and diastole of the left ventricle (±dp/dtmax) with a canula from right carotid to the left ventricle to see the influence of MRI to heart function and the antagonism of losartan to this influence.(3) Measure the myocardial enzyme.(4) Inspect the effect of MRI on AngII in serum and local cardiac muscle with radioimmunoassay.(5) Measure the amount of ATP in myocardial cells after MRI and the change of it with administration of losartan through bioluminescence.2. cell experiment(1) Cultivate myocardial cells primarily from neonatal rats and simulate MRI in vivo by hypoxia and refreshment.(2) Check out the myocardial enzyme and ATP in cultured cells with the same method as that used in animal experiment.(3) Analyze the ultrastructure of those cells after hypoxia and refreshment by electron microscope and also the protective effects of losartan on cell structure Results:1. animal experiment(1) Rabbit's LVSP,dp/dtmax,- dp/dtmax decrease from 101.81mmHg,3822.12mmHg/s,-2985.67mmHg/s in control group to 50.48mmHg,1306.24mmHg/s,-671.17mmHg/s respectively and AngⅡ's concentration becomes 6.22 times of that in control after ischemia for 40 minutes and reperfusion for 2 hours.(2) During the MRI,the concentration of CK,LDH is increasing which after 2 hours'reperfusion becomes 3.57 and 1.69 times of that after 5 minutes'reperfusion and ATP in cardiac muscle is decreasing after 2 hours'reperfusion to 67.95% of that after 5 minutes'reperfusion.(3) AngⅡin serum of operation group ascends apparently from the beginning of reperfusion and goes on during reperfusion which is 6.22 times of that of control group after 2 hours'reperfusion;but AngII in cardiac muscle doesn't change so much which only gets to 2.70 times of that of control group at that time.(4) Losartan can antagonize the damage of cardiac function according to its dosage. For example, LVSP,dp/dtmax,-dp/dtmax of high dosage group are 88.73mmHg,3442.74mmHg /s,-2500.33 mmHg/s respectively.(5)The concentration of CK,LDH in serum of losartan groups also increase but the more losartan there is,the less increase exists.For example,the concentration of LDH in serum of operation group after 2 hours'reperfusion is 1.21,1.36,1.64 times of that of groups with low,medial,high dosage of losartan.(6)The more losartan there is,the slower the increase of AngII in serum is.For example,after reperfusion for 2 hours, AngII of high dosage group is half of that of the low dosage group;while AngII in cardiac muscle increases with the content of losartan.For example,at the time of reperfusion for 40 minutes,medial dosage group contains AngII of 1.42 times of that of low dosage group.(7)The volume of ATP increases with the ascent of losartan dosage.For example,at the time of reperfusion for 2 hours,medial dosage group contains more ATP than low dosage group(P<0.01) and high dosage group contains much more ATP than medial dosage group (P<0.05). 2.cell experiment(1) CK,LDH administer by cells in hypoxia and refreshment group begin to ascend at the beginning of refreshment and goes on continuously which get to 6.4 and 6.5 times of that in control group;group with AngII administers more myocardial enzyme: CK,LDH are 7.33,8.15 times of that of control group;ATP of hypoxia group decreases greatly and group with AngII does more.(2)Mitochondria in control group is intact,in hypoxia group is swelling,in AngII group becomes lysosome and chromosome is condensed and converged to nuclear membrane which is wrinkled.(3)Losartan group contains less CK,LDH compared with hypoxia group which is 89.81% and 51.91% of that in hypoxia group.(4)ATP in losartan groups increases with the ascent of losartan dosage,which in high dosage group is more by 12.53% than hypoxia group;the lysosome disappears,marrow-like structure decreases until it disappears and only occasional vesicles exist.Conclusions:1. MRI can suppress the systolic and diastolic function of rabbit's ventricle and increase the volume of AngII in serum and local myocardial muscle,especially that in serum.2 The concentration of AngII in serum and myocardial muscle has a close relationship with each cardiac index,which is positive with LVDP,-dp/dtmax and negative with LVSP,+dp/dtmax.3 Losartan apparently protects rabbit's MRI heart and antagonize the release of myocardial enzymes,which may be by decreasing AngII in serum and upgrading AT1R so that losartan can cut off AT1R to protect cardiac muscle.4 Losartan may maintain the concentration of ATP in cells to meliorate cardiac function after antagonizing AT1R.5 Cultured cardiac cells can release more myocardial enzymes,maintain less ATP and be more damaged with their ultrastructure after hypoxia and refreshment,during which AngII can aggravate such changes while losartan can mitigate such injuries and AngII's aggravation towards them.
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