| Myocardial infarction (MI) is one of the most life-threatening diseases. Today, it remains to be a suspending problem to improve survival of patients after acute myocardial infarction (AMI), although various therapies have been applied to control morality soon after AMI attacks. VPC was found as a risk factor for MI survivor suffering from sudden cardiac death (SCD), therefore, anti-arrhythmic therapy was tested to protect MI patients from SCD. However, unfortunately, CAST of encainide and flecainide on MI patients suspended due to the markedly increased mortality. Up to now, nothing could improve MI outcome.Arterial baroreceptor reflex (ABR), is the most important self-regulation in the cardiovascular system. And it gains more and more attention after its' protection role to cardiovascular diseases was revealed recent years. La Rovere and Schwartzs found the susceptibility of arrhythmia was increased in MI patients (dogs) with a low ABR function. Thus, we speculate, improving ABR function maybe a new target to improve the outcome of MI. The main object is to search on the mechanism how ABR determines MI rats' outcome.The first step we take was designed to define the relationship between BRS and survival time in rats with coronary artery ligature. It was found, the mortality is much higher in SAD+AMI rats than in AMI rats within 4 hours after LAD ligature, and that of BRS-L group is increased markedly than BRS-H group rats within 24 hours after LAD ligature. In another experiment, it was found rats those died within 6 months had the lowest BRS values, and rats that survived more than 18 months had the highest BRS values. Six months post-operation, mortality was 66.7% (8/12) in MI rats with a BRS <0.35 ms/mmHg, but was only 8.7% (2/23) in MI rats with a BRS >0.5 ms/mmHg. It is concluded that BRS determines survival time after cardiac infarction in rats.And then, we focused on the mechanism of ABR determination on MI outcome.Ventricular arrythmias, heart failure, heart rupture and cardiac shock are the most common reasons causing sudden cardiac death in MI patients, and were considered as the main reason for poor outcome.We compared the incidence of arrhythmias, changes in heart function and heart remodeling between MI rats with low ABR function and normal ABR function. And it was found:1) Incidence of arrhythmia: Incidence of VT in SAD+AMI group rats was much higher than in AMI group rats, and the same as incidence of VF and fatal VF. While in CMI Models, the incidence of total ventricular arrhythmias was increased dramatically in BRS-L group than in BRS-H group.2) Left Ventricular function:In rats with low ABR function, LVSP and +dp/dt , reflecting LV systolic function, were higher in BRS-L than in BRS-H group, while LVEDP and -dp/dt, indicating LV diastolic function, were both declined more significantly in BRS-L group than in BRS-H group. As for the infarcted size (expressed as %), there was no difference between two groups. Thus, we conclude, the difference of LVSP, LVEDP and ±dp/dt between the two groups doesn't owe to infracted size.3) Heart remodelingThe thinning ratio (a/n) in group BRS-L decreased more distinctly in BRS-L group than in BRS-H group. Compared with BRS-H group, BRS-L group's LVRW (LVW/BW) was added notably.We can draw a conclusion here: ABR dysfunction may lead increased incidence of ventricular arrhythmias, aggravating heart function, and accelerate heart remodeling.Further analysis of the complication of MI, we found, electrical remodeling, ventricle remodeling and nerve remodeling may leads to arrhythmias. Ventricular remodeling was affected by neuroendocrine (NE, eg.), RAS activity and apoptosis, and was regulated by inflammatory cytokines. It seems domination of sympathetic and parasympathetic nerve and inflammation were the convergence of all the factors,which constitutes the other part of my dissertation.In the second section of Part2, innervation of sympathetic and parasympathetic nerve in myocardium from infracted area, involved area and non-infarcted area in MI rats were assessed with immunohistochemistry and in situ hybridation methods, and the effect of ABR function on it was investigated. It was shown, one month after MI, autonomic nerve remodeling was shown in infracted area, involved area and non-infarcted area. While a low ABR function contributes to the more sympathetic nerve innervation in infracted and involved area (both beneath the level in sham rat), and the less parasympathetic nerve innervation in all area in rats.In the third section, immunohistochemistry was employed to measure the content of TNF-a, IL-ip and IL-6 in serum, and real-time PCR technique was used to assess the expression of TNF-a, IL-ip and IL-6 mRNA in the heart tissue. Compared to sham group, TNF-a, IL-ip and IL-6 mRNA expression levels increased significantly. Compared to ABR normal group (AMI or BRS-H group), the expression levels of TNF-a, IL-lp and IL-6 mRNA in low ABR group (SAD+AMI or BRS-L group) increased significantly 4 hours or 1 month after MI attack.In the last section of this part, TUNEL was used to evaluate apoptosis of myocardium from involved area. And the effect of ABR function was appraised. As a result, a low ABR function caused a raise of apoptosis index in myocardial of involved area.Conclusion: ABR dysfunction may alter autonomic nerve innervation, exacerbate inflammation and cardiomyocyte apoptosis in rats after MI, and then make them susceptible to fatal arrhythmias and heart failure, which contributes to the poor outcome of rats after MI.
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