Progressive Cardiac Remodeling After Coronary Microembolization In Rats And Effect Of Intervention With Tongxinluo Capsules

Objective The aim of this study was to develop a new model of coronary microembolization (CME) in rats, to explore the changes of myocyte apoptosis,myocardial collagen and intramyocardial arteriole at chronic stage after CME, to determine whether there was a correlation between these changes and cardiac remodeling, and to investigate the effect of intervention of Tongxinluo (TXL) capsules.MethodsThe suspension of 0.2 ml with microthrombotic particles generated from the rat clot were injected into aorta root after clamping the ascending aorta in order to develope a model of CME. Sixty-four rats were randomly divided into four groups: control group, sham group, model group and TXL group. HE staining and Martius-Sarlet-Blue staining (MSB staining) were used to assess microthrombo-embolosim in the coronary microcirculation, and HE staining was also used to detect focal myocardial infarction. TUNEL staining and immunohischemical method for caspase-3 were employed to calculate myocyte apoptosis rate. Sirius-Red staining (SR staining) was conducted to evaluate the content of myocardial collagen, and immunohischemical method for factor â…§ to determine the density of intromyocardial arteriole. Electrical microscopy was performed to detect the changes of myocardiac ultrastructure and serial echocardiography to monitor cardiac remodeling during chronic phase of CME.ResultsValidation of the new model Compared with sham group, both the percentage of arterioles with microembolization and the numbers of focal myocardial infarction were increased in model group (P<0.01), but no significant difference between sham group and control group (P>0.05). The changes of myocyte apoptosis,myocardial collagen and intramyocardial arteriole at chronic phase after CME Myocyte apoptosis rate, the content of myocardial collagen were higher in model group than those of in sham group (P<0.01,each), and the density of intramyocardial arteriole was lower(P<0.01). The changes of ultrastructure in model group included heterochromatin margination in some myocyte and more collagen fibers in myocardium. 3. Correlation between structure changes and cardiac remodeling Compared with sham group, both left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were increased in model group (P<0.01), but left ventricular posterior wall thickness(LVPWT), left ventricular fraction shortering (LVFS) and left ventricular ejection fraction (LVEF) were reduced(P<0.01,each). There was a high correlation between LVEDD, LVESD, LVPWT, LVFS, LVEF and myocyte apoptosis rate, the content of myocardial collagen, the density of intramyocardial arteriole at chronic phase after CME.4. Effect of intervention with TXL capsules Compared with model group, both myocyte apoptosis rate and the content of myocardial collagen were decreased in TXL group (P<0.05), and the density of intramyocardial arteriole was increased (P<0.01). LVEDD, LVESD were smaller in TXL group than those of in model group(P<0.05), but LVPWT was thicker (P<0.05) and LVEF was higher(P<0.01).Conclusions1.A new rat model of CME is created by injection of microthrombotic particles.2.Both myocyte apoptosis rate and the content of myocardial collagen are increased at chronic stage of CME, but the density of intramyocardial arteriole is reduced.3.The changes above lead to progressive cardiac remodeling and dysfunction, CME may be another main mechanism of ischemic cardiomyopathy.4.TXL reduces myocyte apoptosis and myocardial collagen formation with intramyocardial arteriole saving, ameliorating cardiac remodeling and improving cardiac function after CME.