Establishment Of Diastolic Heart Failure Model In Canine With Chronic Myocardial Ischemia And Investigation Of Drugs' Intervention

Objective To establish model of diastolic heart failure in canine mimicking ischemic cardiomyopathy in humans by coronary microembolization with microspheres repeatedly and evaluate the effects of various drugs on Diastolic heart failure(DHF).Methods Canine model of DHF and systolic heart failure(SHF)was produced by coronary microembolization multiply.Before and after last coronary microembolization 1,2,3,4weeks,systolic and diastolic function was assessed by echocardiography and hemodynamics.Successful models of DHF were divided into contrast group(7),metoprolol group(6),enalapril group(6),hydrochlorothiazide group(6),metoprolol+enalapril group(6)and rhBNP group(7)at random.Treated with these drugs for 6 weeks,Systolic and diastolic function was assessed again. Results①DHF were successfully induced in 38 dogs and SHF were 48 dogs.②Compared with the base line,left ventricular end-diastolic pressure(LVEDP), pulmonary capillary wedge pressure(PCWP),time constant of relaxation(τ),left ventricular end-systolic volume(LVSV),left ventricular end-diastolic volume (LVEDV),left ventricular end-diastolic volume index(LVEDVI),left ventricular mass index(LVMI),transmitral E wave decelerating time(DT),isovolumic relaxation time(IVRT),PVa duration-mitral A wave Duration(PVaD-AD),peak velocity of early diastolictransmitral flow(E)/ peak myocardial sustained early diastolic velocity(Em),E/early diastolic flow propagation velocity in LV(Vp) increased significantly(P＜0.01)in DHF group accompanied by significant reductions of mean arterial pressure(MAP),±dP/dtmax,Vp,peak regional myocardial sustained systolic velocity(Sm),peak myocardial sustained advanced diastolic velocity(Am)(P＜0.01)and Em(P＜0.05),however,left ventricular ejection fraction(LVEF)was preserved consistently;In SHF group,LVEDP,PCWP,τ, LVSV,LVEDV,LVEDVI,LVMI,DT,IVRT,PVaD-AD,E/Em E/Vp significantly increased(P＜0.01)and LVEF,fracion of shortness(FS),MAP,±dP/dtmax,Vp,Sm, Em,Am decreased markly(P＜0.01).Compared with DHF group,LVSV,PVaD-AD, E/Em,E/Vp(P＜0.01)τ,LVEDV,LVEDVI,DT(P＜0.05)increased significantly and LVEF,FS,Sm,Em,Am(P＜0.01)left ventricular systolic pressure(LVSP),±dP/dtmax(P＜0.05)decreased.③Compared with contrast group,each drugs increased Sm,Em,Am and Vp significantly(P＜0.01),in the same time,significantly decreased LVEDP,τ,LVMI,DT,IVRT,PVaD-AD,E/Em,E/Vp(P＜0.05)at 6 weeks after management.PCWP was decreased significantly in combination of metoprolol+ enalapril group,RhBNP group and hydrochlorothiazide group(P＜0.05). HR decreased in metoprolol group conferring to contrast group(P＜0.05).④Compared with hydrochlorothiazide group,LVMI decreased significantly in combination of enalapril group,metoprolol+ enalapril group and RhBNP group (P＜0.05),LVEDVI decreased significantly in enalapril group(P＜0.05),Em increased significantly in enalapril group and metoprolol group.E/Em in hydrochlorothiazide group was lower than in other drug groups(P＜0.01)and heart rate in metoprolol group reduce markly conferring to other drug groups(P＜0.05).⑤By Masson staining,compared with contrast group,enalapril group,metoprolol+ enalapril group and RhBNP group significantly lessened the injury of myocardium and myocardial fibrosis.Conclusion①It is suggesting that canine model of DHF was established successfully.②we detect that DHF are often associated with mild systolic dysfunction.③DHF caused by myocardial ischemia repeatedly may be the pilot process of SHF.④Metoprolol,enalapril,hydrochlorothiazide and rhBNP can improve the diastolic and systolic function of DHF,in which metoprolol+enalapril and rhBNP have the best curative effect.⑤Enalapril inhibit left ventricular reconstitution bestly,metoprolol refer to curing DHF with rapid heart rate and hydrochlorothiazide can improve symptom of DHF effectively.