Combination Of Isosorbide Dinitrate And Hydralazine In Rats With Chronic Heart Failure

BACKGROUND Chronic heart failure(CHF) is still a serious disease despite its mortality rate has been decreased.The African-American Heart Failure Trial(A-HeFT) come to the conclusion that based on standard anti-CHF therapy,the additional administration of HYD plus ISDN to CHF patients could benefit more.The underlying mechanism remains elusive and the effect of HYD plus ISDN on other population is unknown.Objective To investigate wether the additional benefit effect of HYD plus ISDN could be repeated in rats and their effect on collagen proliferation in myocardial matrix.Methods This is a two-stages experiment.In the first stage,120 rats were randomly devided in to two group:control group(C group,n = 10) and adriamycin group(ADR group,n = 110).Six equal does injections(2.5mg/kg·d) of ADR were administrated to rats in ADR group and C group receive equal volume of normal saline(NS).In the second stage,after four weeks of the last injection,rats in ADR group were randomly devided into three group:NS group (n=24),Perindopril(Peri) and Bisoprolol(BSP) group(P-B group,n = 23) and HYD plus ISDN group(H-I group,n = 23).P-B group was given 2.5mg/kg·d Peri and 5mg/kg·d BSP,H-I group was given 2.5mg/kg·d Peri,5mg/kg·d BSP, 7.2mg/kg·d and ISDN 6mg/kg·d.,NS group was given equal does of NS.Left ventricular ejection fraction(LVEF),left ventricular Internal dimension-diastole (LVIDd) and left ventricular internal dimension-systole(LVIDs) assessed by M-mode ultrasound were used to evaluate heart function.Survival rates and heart wight(HW)/body weight(BW) were calulated.Collagen proliferation in myocardial matrix was evaluated by assessing hydroxyproline(HYP) content in myocardial tissue,picrosirius red staining of sections of myocardium,and experssions of typeⅠand typeⅢcollagen protein mRNA.Result The accumulative survival rates of NS group,P-B group and H-I group were 25%,56.5%and 60.8%respectively.Significant differences were observed between P-B group and NS group,as well as H-I group and NS group. No significance could be found between P-B group and H-I group.LVEF, LVIDd and LVIDs in rats in both P-B group and H-I group were significantly improved at the end of the experiment,compared with before giveing these drugs.At the end of the experiment,heart function in P-B group and H-I group were better than NS group.Heart function was similar in P-B group and H-I group.The value of HW/BW in P-B group and H-I group was significantly smaller than it in NS group,but was not significant between P-B group and H-I group.HYP content,picrosirius red staining of sections of myocardium and expressions of typeⅠand typeⅢcollagen protein mRNA have consistently indicated that collagen proliferation in not as serious in P-B group and H-I group as in NS group;but it was similar in P-B group and H-I group.Conclusion Additional adiministration of HYD plus ISDN could not further improve survival rates or heart function of CHF rats;nor could it further inhibit collagen proliferation in myocardial matrix.