Impact Of Ivabradine On Left Ventricular Dysfunction And Cardiac Fibrosis

Objective: Investigate the effects of ivabradine on left ventricular function and cardiacfibrosis of rabbits with heart failure.Methods:⑴34male New Zealand rabbits weredivided into tow groups randomly: Sham group and heart failure group. The heart failuremodels (n=28) were established by aortic insufficiency, or aortic insufficiency plusabdominal aorta constriction. Sham group were established by sham operation (n=6). Afterthe abdominal aorta constriction finished at the4th week, heart failure rabbits wereassigned to be received ivabradine by water randomly,then the heart failure group would bedivided into untreated and ivabradine(IVA) groups.⑵Ten normal rabbits were drawrandomly and recorded their Left ventricular (LV) M-mode spectrum was obtained. tomeasure LV diameters at both end cardiac interior diastole (LVIDd) and systole (LVIDs).LV fractional shortening was calculated as (LVDd–LVDs)/LVDd×100%.Pulsed waveDoppler was used to evaluate transmitral flow in apical4-chamber view. The peakvelocities during early filling (E) and atrial contraction (A) were measured by transmitralflow and the E/A ratio was calculated.Mitral annulus velocities during early filling (Em)and atrial filling (Am) were derived by tissue Doppler imaging. Record the images againafter the heart rate decreased by injecting ivabradine.⑶Transthoracic echocardiographicstudies were performed before operation, at4th week and before sacrifice,2Dechocardiography images, mitral flow pattern, mitral velocity were recorded.⑷Leftventricular catheterization was performed before sacrifice.(5)Fibrosis area quantificationwas prepared by Masson’s Trichrome-stained sections.MMP-2and MMP-9relativeexpression quantity determined by Real-time PCR.Results:⑴Intravenous application of ivabradine hydrochloride can make the experimentalrabbit HR decreased significantly (P<0.01), IVRT increased significantly (P<0.01), and thecardiac function indexes LVEF, FS, FAC, E/A, E/Em had no significant effect(P<0.05).⑵Compared with the sham group,untreated group and IVA group had hiaherLVIDd, LVIDs, LVPWd, E/Em and IVRT, but LVEF, FSA, FAC, E/A and Em/Am were lower (P<0.01or P<0.05). IVA can effectively improve heart failure rabbit LVEF, Em/Am,E/Em, the difference was statistically significant (P<0.05).⑶Compared with the shamoperation group, heart failure group HR, ASBP, ADBP,±LVdp/dtmax absolute valuedecreased, the differences were statistically significant (P<0.01). Heart failure IVAtreatment group HR, ASBP, APP decreased significantly, and the ADBP,±LVdp/dtmaxabsolute value had no significant effect, with statistical significance (P<0.01orP<0.05).⑷Compared with the sham operation group,the other two groups’collagen volumefraction (CVF) increased significantly, while MMP-2and MMP-9expressed more,statistically significant (P<0.01). IVA can be effective in reducing heart failure rabbit heartwith CVF, MMP-2and MMP-9mRNA expression (P<0.05).Conclusion:(1) Ivabradinehydrochloride can quickly reduce the rabbits’HRs without affecting blood flow, so as toobtain a clearer mitral flow and tissue Doppler image in order to get a more accurateechocardiography data.(2) Hydrochloride ivabradine can improve left ventricular systolicand diastolic function, and significantly reduced left ventricular myocardial fibrosis.