| Part I The influence of neuregulin-lon systolic and diastolic functionof rats with heart failureOBJECTIVE: To examine the effects of monotherapy with neuregulin-1 on systolic and diastolic cardiac function in rats with chronic heart failure(HF).MWTHODS: myocardial infarction was inducted in adult male SD Rats by ligation of left coronary artery. Sham-operated rats(n=8) experienced identical surgery without ligation. 3 months later, survivors were examined with echocardiogram. 36 rats that had an infarct area and a EF around 60% were randomized into 3 groups : MI group(n=12) were injected a blank vehicle fluid intravenously for 5 days, after which they continued to be raised on standard food and water for 30 days. MI+NRG group(n=12), received NRG-1 10μg . kg-1 intravenously for 5 days, after which they continued to be raised on standard food and water for 30 days. MI+Capt group (n=12) received captopril orally (dissolved in their drinking water 2g/L)for 30 days , after which tap water substituted the solution for 5 days. At the endpoint of the treatment, the changes of cardiac function were measured with echocardiogram , hemodynamic data was collected after the final echocardiographic assessment.RESULTS: Baseline measurements showed that heart failure were successfully produced in animals. Cardiac function had no statistical difference between groups except for the sham group. At the endpoint of the treatment, EF of MI+NRG-1 group was found to be higher than untreated MI group( 0.830+0.056 vs. 0.684+ 0.117,p=0.009), FS of MI+NRG-1 group is also higher than untreated MI group (p=0.008) .MI+Capt group had a similar EF and FS with MI+NRG group (p=NS) . Evaluated with echocariogrphy,NRG-l therapy markedly improved systolic function of the failing heart, whose effect is as good as, if not better than captopril. Hemodynamic measurements showed that MI+NRG-lgroup had a higher dp/dtmax (5122. 52 ± 1063. 09 vs. 3323. 35 + 756. 29, p=0. 000) and a lower -dp/dtmin(-3464.50 ±347.06 vs. -2324.52+634.27, p=0.000).NRG-l treatment also had beneficial effects on LVPmax> LVPmiru DBP.CONCLUSION: NRG-1 treatment markedly improved the systolic and diastolic function of the failing heart. It seemed that these effects were not achieved by lowering the blood pressure of animals.Part II The influence of neuregulin-lon histologic and morphometric presentations of rats with heart failureOVJECTIVES: To examine the influence of neuregulin-lon histological and morphometrical presentations of rats with heart failure, in order to understand the influence of NRG-1 on left ventricle remodeling.METHODS: Echocardiogrphy measurements was accessed in animals other than sham group, including left ventricle diameters , septum thickness, and posterior wall thickness. Animals were sacrificed . Body weight and heart weight were recorded, Lungs were isolated, weighed at both moments of immediately after sacrifice and drying. Heart-to-body weight ratios and lung wet-to-dry ratios were calculated to access ventricular hypertrophy and lung congestion, heart weight/body weight were calculated. The apex was fixed with 10% formalin and paraffin embedded .6 sections at 1mm interval were selected, stained with HE, Masson staining for morphologic and histologic study. Collagen area fraction was calculated ,using microscope and corresponding software. Vessel density , thickness of RV and infracted area of LV were also measured for statistical analysis.RESULTS: There were no difference in PW,IVS, LVDd among groups(p=NS) , animals in MI+NRG-1 group had a lower LVDs than those in untreated MI group (0.393 + 0.072 vs. 0.507+0. 102, p=0. 023) . By Calculating heart-to-body weight ratios, no significant differences were found among groups. Animals in MI+NRG-1 group had a lower lung wet-to-dry ratios than those in MI+Capt group. (2.6915 + 0.6843 vs. 3.8374 + 0. 5312, p=0. 045) Collagen was seen accumulated around small vessel in a very low amount( |
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