| Congestive heart failure (CHF) is the end stage of many cardiac diseases, and the incidence of CHF is increasing, which results in significant disability and mortality, and AMI is the leading underlying cause of CHF. Heart transplantation is an effective treatment stratege for patients with end stage heart failure, however, shortage of donor organs is the biggest obstacle in the rapid development of heart transplantation. Left ventricular assist device (LVAD) are used to hemodynamically support heart failure patients awaiting for an donor organ as a bridge to transplantation. Interestingly, a few studies have recently reported significant left ventricular function improvement in some patients in end stage CHF supported with LVADs. Clearly understanding this apparent functional recovery process in state of mechanical low-loading would help us develop new treatment strategies of CHF in molecular level.Rat is the mostly common used animal in experimental research in cardiovascular diseases. Geometric and functional change process following acute transmural anterior myocardial infarction in rats is similar to that seen in humanbeings, and it is often used in the study of CHF. With the development of clinical ultrasound and the use of high frequency probe, it is now possible to observe the cardiac structure and function of small animals by echocardiography. High resolution and high frame rate echocardiography provides real-time, consecutive assessment of structure and function of rat heart. Quantitative tissue Doppler imaging (QTDI) is a new promising technique which made it possible to evaluate regional ventricular myocardial function. In the present study, heart failure was induced in Lewis rats by ligating the left anterior descending artery followed by large myocardial infarction. Then, the failing hearts were heterotopically transplanted to the necks of recipient Lewis rats. Only coronary circulation was maintained in transplanted heart, the preload of the failing heart decreases significanly, which can partialy reproduce the situation with a LVAD. The left ventricular structure and systolic function alterations after infarction and the effect of heterotopic transplantation on them were assessed using high frequency echocardiography and QTVI technique. Moreover, β-adrenoreceptors mRNA expression in the myocardium of failing heart after mechanical low loading was evaluated. The study was divided into three parts as follows:Part 1. Assessment of left ventricular geometry and systolic function after acute large myocardial infarction in rats using high frequency echocardiographyThe aim of this part was to observe left ventricular geometry and systolic function in rats after acute large anterior myocardial infarction using high frequency echocardiography combined with QTVI technique, and to assess the value of echocardiography in the evaluation of rat failing heart model after acute myocardial infarction.Results: ①left venticular long axis view, short axis view at papillary level and apical four-chamber view were obtained in all rats using a 11.4MHz probe. ②5 weeks after ligation, LVEDD, LVEDV, LVESD, LVESV of infarcted rat hearts significantly increased compared with those of sham ligation group; IWT decreased (P<0.01) with hypokynetic or akynetic; PWT had no change (P>0.05); LVM increased (P<0.01); PWTR, FS and EF significantly decreased (P<0.01). ③ Peak systolic velocity at basal and middle segments of posterior interventricular septum, as well as those of left ventricular lateral wall were much lower in infarcted group than in sham ligation group. ④LVM derived from echocardiography correlated well with the value from postmortem measurement, r value was 0.87 in infarcted group, and 0.94, in sham ligation group.Part 2. Evaluation of the effect of mechanical low-loading on left ventricular geometry and systolic function of failing rat heart using high frequency echocardiographyIn this part, we used the cervical hetetotopic cardiac transplantation model in rats to reproduce the situation with a LVAD, and investigate the reverse remodeling and functional recovery of the infarcted failing heart in the situation of mechanical low-loading after heterotopic tranplantation using high frequency echocardiography and quantitative tissue velocity imaging ( QTVI).Results: ①After 2 weeks of mechanical low-loading, LVEDD and LVEDV significantly decreased ( P<0.01 ), so did LVESD and LVESV ( P<0.05 ); PWTR and LVEF significantly increased ( P<0.05 ), and LVM decreased ( P<0.05 ); ②The peak systolic velocity at basal and middle segments of posterior interventricular septum, as well as the peak systolic velocity at basal segments of left ventricular lateral wall significantly increased ( P<0.05 ). ③ Compared with failing hearts without transplantation, myocyte diameter of transplanted hearts was smaller ( P<0.05 ), and the fibrotic area percentage had no differences between two groups ( P>0.05 ).Part 3. Evaluation of the effect of left ventricular low-loading on β-adrenoreceptors gene expression of failing rat heartIn this part, we observe β-adrenoreceptors mRNA expression in the rat model of heart failure and evaluate the effects of left ventricular low loading on it. Therefore we can make the initial exploration of cardiac function recovery mechanism of failing heart in state of low loading at molecular level.Results: The expression levels of β1-AR mRNA significantly decreased in the infarcted group compared with the control group (P<0.01) , and the expression levels of β-3AR mRNA increased (P<0.01) . After 2 weeks of unloading, the expression levels of β1-AR mRNA improved (P<0.01) and the levels of β3-AR mRNA decreased(P<0.05). There was no statistically significant difference in expression levels of β2-AR mRNA among 3 groups.ConclusionsUnder the conditions of the present experimental study, our conclusions are as follows: ①Left ventricular geometric alterations after acute large anterior myocardialinfarction, called left ventricular remodeling, will finally cause left ventriculardysfunction and contribute to the development of CHF. ② High frequency echocardiography combined with QTVI technique providereal time and consecutive assessment of left ventricular geometry, globaland regional systolic function. ③ The hetetotopic cardiac transplantation model in rats can partially reproducethe situation of hemodynamical support with an LVAD in heart failure patients, and it provides an available experimental method to study function recoverymechanisms with the use of LVAD.④left ventrucular reverse remodeling and functional recovery of the infarctedfailing heart can be observed in the situation of mechanical low-loading afterheterotopic tranplantation.⑤Mechanical low loading can help normalize β-ARs gene expressioninmyocardium of failing heart, the recovery of β-ARs gene expression may beone of the reasons of functional recovery of failing hearts with the use ofLVAD. |
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