Acute Myocardial Infarction And Reperfusion Combined With Early Metoprolol Treatment, Basic And Clinical Research

Background and Objective:The animal model of Acute Myocardial Infarction (AMI) is very important for the study of AMI. Compared with coronary artery ligation and coronary artery stimulus, the method that uses interventional techniques to establish AMI model is the new approach for create the model of AMI. However, the difference of coronary artery and aortic arches between animal and human beings is the biggest handicap of this approach.In accordance with anatomic characters of coronary artery, different ventricular regions requires different coronary branch to supply blood and nutrition. Conventional method, which can measure heart function invasively, can't analyze its function quantitatively. Whereas Tissue Doppler Imaging (TDI) can measure the systolic and diastolic velocity and time directly, it provide a new method for evaluation regional ventricular function.Acoustic Quantification (AQ) allows online tracking of changing LV area over time and a curve of the rate of area change over time can be displayed, it can measure systolic and diastolic function of every chamber accurately. The existing data show that results of AQ are correlated well with the results of interventional techniques and MRJ. This novel technique allows convert volume-time curve to the rate of volume change-time curve and thus allows display the rate of volume change, namely thecapability of volume change or systolic and diastolic function over time, allow us to evaluation ventricular systolic and diastolic function systematically.There were many studies that concern hemodynamics alteration in AMI, but there were little studies aimed at research early hemodynamics change in AMI, especially in 24 hours after onset of symptoms, using TDI and AQ estimate ventricular global and regional systolic and diastolic function in early stage of AMI.Results of many clinical trial recommend P adrenoreceptor blockers should be used as quickly as possible in case of AMI. However little has been known about its effect on hemodynamics, and little material which concern theoretical mechanism of large clinical trial and the dose of ï¿¡ adrenoreceptor blockers can be obtained. The present study aimed at:1. Modify the guiding catheter that were used for canine coronary angiography and made the catheter more convenient when used in experiments for coronary angiography balloon and stent implantation. Using the modified catheter and guiding catheter to establish canine model of AMI.2. Based on the canine model, regional myocardial systolic and diastolic function of infarct-related regions of left ventricule has been monitored dynamically for 24 hours, and compared with infarct-irrelevant regions; we studied the dynamical change and coordination mechanism of early infarct-related regions and infarct-irrelevant regions.3. Based on the canine AMI model, we monitored the left ventricular global systolic and diastolic function dynamically for 24 hours. The results were compared with that of left ventricular regional systolic and diastolic function obtained spontaneously. We studied the relationship between early function of infarct-related regions and global ventricular function. We also studied the mechanism and importance of early myocardial remodeling.4. Based on the canine AMI model, we monitored left ventricular global and regionalsystolic and diastolic function of experimental animals which were treated with metoprolol, and compared those results with the results of control group.We studied the mechanism of ï¿¡ adrenoreceptor blockers on improving ventricular function, and tried to provide theoretical basis for large clinical trial and clinic use of P adrenoreceptor blockers in early stage of AMI. Materials and Methods:The subjects include 15 hybrid canines. According to the study project, the canines were divided into two groups, namely, AMI group and AMI treated with metoprolol group. Subsequently the two groups were divided into AMIlh, AMBh, AMI6h, AMI12h and AMI24h subgroups according to experiment time. Anterior descending branch were occluded by ballon to establish AMI model. Two-dimensional Echocardiogrphy, TDI and AQ were used to measure following index:1. V^ V-D> V-A and V-D/V-A of infarct-related regions and infarct-irrelevant regions.2. EDV > ESV, SV > LVEF ^ CO ^ PER-LV and PFR-LV of global left ventricular function.Results:15 canines were used in the experiments. All animals completed coronary angiography, balloon implantation and AMI mode establishment, except one canine died for ventricular fibrillation. All canines of metoprolol treated group completed the study with the same dose of metoprolol.1 .The results of two-dimensional Echocardiography and AQ before and after AMI were listed in table 1. This list reflected the animal global systolic and diastolic function of left ventricule.1) Post AMI lh, the animal's heart rate increased, the dimension of ventricular chamber decreased, EF decreased, but the cardiac output can sustained; the globalleft ventricular systolic and diastolic function decreased significantly2) Post AMI 3h, the animal's heart rate sustained at high level, there no significant changes of left ventricular dimension, cardiac output and EF decreased significantly; the global left ventricular systolic and diastolic function decreased significantly.3) Post AMI 6h, the animal's heart rate become lower, the dimension of ventricular chamber increased, cardiac output and EF sustained; the global left ventricular systolic and diastolic function decreased more significantly.4) Post AMI 12h, the animal's heart rate become lower, EF sustained, the dimension of ventricular chamber increased significantly, cardiac output increased little; the global left ventricular systolic and diastolic function recovered little.5) Post AMI 24h, the animal's heart rate become lower, EF sustained, the dimension of ventricular chamber increased continuously, cardiac output increased; the global left ventricular systolic and diastolic function recovered little.2.The results of TDI before and after AMI were listed in table 2.This list reflecting the animal regional systolic and diastolic function of left ventricule.1) Myocardial velocity of left ventricular lateral wall was higher than that of middle ventricular septal.2) During anterior descending branch occluding, the velocity of ventricular septal decreased significantly; Va-S which reflecting systolic function and Va-D which reflecting diastolic function decreased significantly; but Va-D/Va-A which can reflect diastolic function more accurately recovered in 12h, 24h after AMI.3) During anterior descending branch occluding, the velocity of left ventricular lateral wall was lower than velocity of ventricular septal; with the occluding time prolonged, the index of systolic and diastolic function decreased slowly, after 12-24 hours, the difference become similar.3.The results of two-dimensional Echocardiography and AQ of the canine treatedwith metoprolol1) The moment treated with metoprolol resulted in heart rate decreased significantly; ventricular chamber increased (compared the results before and after AMI, it reflect the chamber can relax sufficiently); SV, EF and CO decreased.2) The moment treated with metoprolol the global left ventricular systolic function improved, similar to the chamber change of non-treated group 12-24 hours after AMI, but the chamber dimension smaller than non-treated group.3) Treated with metoprolol during 12 hours, ventricular chamber smaller than that of control group, the global left ventricular function improved, and there was no difference between two groups at 24 hours after AMI.4. The results of TDI of the canine treated with metoprolol1) The moment treated with metoprolol, the heart rate decreased while myocardial velocity increased, Va-S which reflecting systolic function and Va-D, Va-D/Va-A which reflecting diastolic function increased significantly.2) After treated with metoprolol, the velocity of infarct-related regions and infarct-irrelevant regions become similar and harmonious, compared with control group treated with metoprolol can keep harmonious motion and can keep myocardial regional systolic and diastolic function.Conclusion:1. We were succeeded in using modified catheter and guiding catheter to establish canine AMI model.2. TDI can assess regional ventricular function in early AMI more sensitively and more accurately and it is an ideal method to evaluate ventricular function invasively.3. AQ is a practical technique that can dynamically assess global ventricular systolic and diastolic function in different state and in different load with the character of comprehensive, real-time, objective.4. Early ventricular remodeling can reflect regional and global ventricular functional changes of self-adaptation.5. Treated with metoprolol early after AMI can decrease heart rate, myocardial oxygen consumption; increase SV and improve global and regional ventricular systolic and diastolic function effectively.6. Treated with metoprolol early after AMI can regulate early ventricular remodeling process, made this self-adaptive process complete earlier and in time; prevent over-adaptation and prevent late stage remodeling.7. This study indicated that using large dose of metoprolol in early stage of AMI is safe and effective.