| Background:Chronic heart failure is the end state of various heart diseases, highmortality, is similar to malignant tumor. Heart failure is a complex clinical syndrome, hasbecome one of the most serious medical problem of the century. Traditional inotropic drugsbecause of their disadvantages, its application is more or less restricted to a certain extent, inwhich Ca2+is the crux of the problem: the effect on myocardial relaxation, increasedmyocardial oxygen consumption, malignant arrhythmia induced flow within the Ca2+,increased mortality. Calcium sensitizer allow clinicians to see new hope, levosimendan asone kind of talent showing itself. At present, heart failure assessment of drug efficacy thanusual method (symptoms, cardiac function, cardiac ultrasound), increasing the biomarkerevaluation is beneficial, and worth promoting. The commonly used marker of clinical mainlyamino terminal pro brain natriuretic peptide (NT-ProBNP). Insulin like growth factor1(IGF-1), cardiac troponin T (CTnT) is the latest assessment of curative effect of heart failure and drug targets, but the clinical application is not widespread.Objective:To assess the efficacy of levosimendan compared with conventional treatmentheart failure drugs in chronic heart failure.Methods:80Patients were arranged into this randomized,parallel-group and positivestudy to receive either levosimendan or conventional treatment for heart failure.40wereassigned to levosimendan and the other40were to conventional treatment group. These twogroup patients were both monitored vital sign，degree of dyspnea and overall clinicalstatus,level of IGF-1,CTnT, NT-proBNP and hemodynamic index variables before and72hours after treatment.Results:74patients were included in the results of the analysis.Among of them,36werelevosimendan group,38were control group. The clinical efficacy rate was83.3%（30/36） in levosimendan group and55.3%（21/38）in control group（P=0.027）.72hoursafter treatment， insulin-like growth factors(IGF-1) was increased by44.6ng/ml inlevosimendan group,6.8ng/ml in control group(P=0.018). Cardiac troponin T(cTnT) wasdecreased by40.3pg/ml in levosimendan group,compared with11.3pg/ml in controlgroup(P=0.015). N-terminal pro-brain natriuretic peptide(NT-proBNP) was decreased by2958pg/ml in levosimendan group,compared with1936pg/ml in control group(P＞0.05).Systolic blood pressure(SBP) was decreased by16.15mmHg in levosimendan group and6.14mmHg in control group（P=0.044）.DBP was decreased by20.62mmHg in levosimendangroup and10.75mmHg in the other respectively（P=0.015）.Heart rate was reduced by6.65beats/min in levosimendan group and2.82beats/min in the othe（rP＞0.05）.There was nosignificant defference in the incidence of adverce reaction between the two groups (P＞0．05).Conclusion: Blood cTnT, IGF-1can accurately evaluate levosimendan efficacy of thetreatment of chronic congestive heart failure, which is more sensitive than NT-proBNP. Objective Nicorandil belongs to nitrate compounds, has prevented the intracellular freecalcium, increasing cell membrane permeability to potassium ions, dilating coronary artery,persisting increased coronary blood flow, inhibit the role of coronary artery spasm, alsoinhibit platelet aggregation to prevent the formation of thrombus. Clinical studies havedemonstrated that, it is suitable to be used in treatment of various types of angina pectoris,and can significantly reduce the risk of cardiovascular events, improve the prognosis. But ifnicorandil for heart failure (especially ischemic heart failure) could improve the prognosticrole is not clear. This study intends to impact assessment of nicorandil on cardiac function ofischemic heart failure, and to explore the possible mechanism of nicorandil.Method1.experimental groups: Adult SPF level of30SD rats, male, were randomly divided intothe nicorandil group12: third days in the ligation of the left coronary artery was givenintragastrically after nicorandil until eighth weeks after surgery. The6rats in the shamoperation group: rat thoracic, do except for the ligation of coronary artery, over the sameperiod equal dose distilled water. The control group12rats: rats only occlusion of the leftcoronary artery, not to give medicine. Nicorandil group received nicorandil3mg· kg-1· D-1Ig, from the third day after surgery was continued until eighth weeks after surgery; shamoperation group and control group with equal volume of double distilled water gavage. All therats in each group after eighth weeks of each index test.2.general conditions: To observe the general condition of rats body weight, respiration,activity, hair color after operation, according to the weekly record of weight, adjustment ofintragastric dose.3.eighth week after operation with a small animal blood pressure measurement of bloodpressure in rats.4.eighth weeks after surgery with small animal ultrasound cardiac function of rats in eachgroup Heartbeat detection instrument.5.rats with left ventricular mass and lung weight detection: open the chest, quickly remove the heart, electronic balance to weigh accurately left ventricular weight, with quality, tocalculate the left ventricular mass/body mass, representing the left ventricular hypertrophyindex. Then the lung mass, calculation of lung weight/body weight, reactive hyperemia.6.routine HE staining, observe the morphological changes of myocardial tissue in rats indifferent groups of microscope.7.immunohistochemical analysis of the content of apoptosis protein Bax in myocardialtissue of rats in each group.Result1.general situation: the sham operation group rats is sensitive, active, into a normal diet.Heart failure rats activity decreased gradually, mental fatigue, after4weeks in the visibleshort of breath, even wheeze appearance, weight loss, hair dark less shiny. After8weeks,weight was significantly lower than the sham operation group and nicorandil group. Bodyweight and mental activity, nicorandil group were significantly better than the heart failuregroup.2.blood pressure measurements in three groups of rats: systolic blood pressure, heart failuregroup than in sham operation group, the difference was statistically significant (P <0.05);nicorandil group is less than the other two groups, the difference was statistically significant(P<0.05). Three groups of rats diastolic blood pressure, nicorandil group was significantlyless than the other two groups (P<0.05); compared with the sham operation group and heartfailure group, no significant difference (P>0.05).3.ultrasonic Beckoning cardiac function map in rats: the rats left ventricular ejectionfraction (EF%), heart failure group was smaller than the nicorandil group, nicorandil groupthan in sham operation group; the difference was statistically significant (P<0.05); leftventricular short axis systolic fraction of rats (FS%) compared with heart failure group wassignificantly less than: sham operation group (P<0.05), no difference between nicorandilgroup and sham operation group (P>0.05). E/A comparison, nicorandil group and heartfailure group, were less than sham operation group, the difference was significant (P<0.05);heart failure group was smaller than the nicorandil group, there was statistically significantdifference between them (P<0.05). Left ventricular end diastolic volume (LVEDV), shamoperation group was smaller than the other two groups, the difference was statisticallysignificant (P<0.05); heart failure group than nicorandil group (P<0.05). End systolic leftventricular volume (LVESV), heart failure group than in the other two groups (P <0.05); butcompared with sham operation group and nicorandil group, the difference was not statisticallysignificant. Left ventricular end diastolic diameter (LVIDd) and end systolic diameter (LVIDs) for heart failure group than in the other two groups (P<0.05); but compared with shamoperation group and nicorandil group, the difference was not statisticallysignificant.Interventricular septal thickness (IVSd) there was no significant differencebetween the three groups.4.left ventricular mass and lung weight detection: Nicorandil group LVW/BW wasobviously lower than that of heart failure after myocardial infarction model group (P<0.01),LUNGW/BW was also lower than the heart failure group (P<0.01); heart failure group andLVW/BW, LUNGW/BW were higher than the sham operation group (P<0.05).5.Morphologic changes of cells were observed: sham operation group rats myocardial cellswere arranged in order, and the myocardial cell morphology clear stripes of heart failure ratsvery irregular, disordered, large amounts of fibrous tissue hyperplasia. Nicorandil group:compared with the sham operation group, the rat myocardial cells arranged in disorder, theproliferation of fibrous tissue; compared with heart failure group, rat myocardial cellsarranged in neat rows, the degree of fibre hyperplasia significantly reduce.6.The expression of Bax in myocardial tissue of5in rats: compared with the shamoperation group, the content of Bax protein in heart failure group and nicorandil group ratcardiac tissue increased significantly, significantly (P<0.01); compared with heart failuregroup, the expression of myocardial tissue in rats of nicorandil protein significantly decreased(P<0.05).Conclusion1.Nicorandil can effectively improve myocardial hypertrophy in rats with ischemic heartfailure and myocardial remodeling, improve left ventricular ejection fraction, cardiac functionindex, has protective effects on myocardial.2. Nicorandil can down the expression of regulate Bax expression, inhibit the apoptosis ofmyocardial cells, improve heart function.3.Nicorandil can decrease blood pressure, but has little effect on the heart rate, andmaintain stable hemodynamics. |
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