The Expression of β3-adrenoceptor of Left Ventricle and the Effect on Heart Function by Stimulating β3-AR in Rats With Experimental Heart Failure

Objectives To observe the expression of β3-adrenoceptor （β3-AR） of left ventricle and the effect on heart function by stimulating β3-AR in rats with experimental heart failure. Methods Rats were randomly divided into heart failure group and control group. Heart failure models were built up by ligating coronary artery in rats. The expression of β3-AR mRNA were detected with RT-PCR; The change of heart function were observed after administration of BRL37344 （β3-AR agonist） by measuring left ventricular end-systolic pressure （LVESP）, left ventricular end-diastolic pressure （LVEDP）, the maximum pressure ascending rate of left ventricle （＋dp/ dtmax） and the maximum pressure descending rate of left ventricle（-dp/dtmax）. Results The expression of β3-AR mRNA （β3/β-actin） was 0.028±0.005 and the proportion of β3-AR （β3/β1＋β2＋β3） was 5.4%±0.06% in failure rats while the expression of β3-AR mRNA was 0.011 ±0.004 and the proportion was 1.2%±0.04% in control rats; The descending percentage of LVESP, ＋ dp/dtmax and -dp/dtmax were 16.1%, 21.7% and 13.2% respectively with administration of BRL37344 in failure rats, while 12.2%, 15.8% and 11.5% in control rats. Conclusions Compared with control group the expression of β3-AR mRNA of left ventricle was obviously increased and the negative inotropic function with exciting β3-AR was obviously enhanced in failure groups.     

Effect of β3-adrenoceptors on Ventricle Fibrillation Threshold and Effective Refractory Period in Rats With Heart Failure

Objectives To observe the effect of β3-Adrenoceptor （AR） on ventricle fibrillation threshold （VFT） and effective refractory period （ERP） in rats with heart failure. Methods Rats were randomized into control group and heart failure group. The expression of β3-ARmRNA was detected with RTPCR; The VFT, ERP, LVESP,LVEDP, ＋dp/dtmax and -dp/dtmax was measured at the same time with administration of BRL37344 （ 2 nmol / kg, β3- AR agonist）. Results ①Both the expression of β3-AR mRNA and the proportion increased in rats with heart failure in comparison with control rats （0.028 vs. 0.011 and 5.4% vs 1.2%, P 〈 0.05）;② ERP was longer in rats with heart failure than control group （70.5±5.5 ms vs 59.5±6.4ms, P 〈 0.05） and there was no difference of ERP in rats with heart failure with administration of BRL37344 （73.0±4.8 ms vs 70.5± 5.5 ms, P 〉0.05）; ③VFT was lower in rats with heart failure than control group（10.9±0.8 mv vs 30.5± 1.3 mv, P〈 0.05） and decreased obviously in rats with heart failure with administration of BRL37344 （7.1±0.6 mv vs 10.9±0.8 mv, P 〈 0.05） ; The decrease of VFT correlated with the effect on LVESP, ＋dp/ dtmax,-dp/dtmax of BRL37344 and the expression of β3-AR mRNA （correlation coefficient： 0.788, 0.708, 0.759, 0.787; P 〈 0.05）. Conclusions The expression of β3-AR mRNA of left ventricle was obviously increased in rats with heart failure, and activation of β3-AR had no effect on ERP but could decreased VFT which correlated with the effect of β3-AR on LVESP, ＋dp/dtmax, -dp/dtmax and the expression of β3-AR mRNA.     

The Regulation Effects of β2-AR on INCX in Myocytes from Infarcted Rat Heart

Objectives This study is designed to investigate the regulation effects of β2-adrenergic receptors （AR） on expression of the Na^± - Ca^2 ± exchanger （ INCX） in myocytes from the infarcted rat heart. Methods Twenty-eight adult Wistar rats were randomly divided into four groups ： the control group, the two weeks, four weeks and eight weeks post-myocardial infarction （post-MI） groups, respectively. The chest of rat was opened and a ligature was placed around the left anterior descending coronary artery. Rats in control group were sham-operated without the coronary artery ligation. After the operation, rats were fed for two, four or eight weeks respectively. Myocytes were enzymatically disassociated by Langendorff perfusion. The whole cell-patch clamp recording technique was used to record INCX in specific pipette solution and superfusion according to the specific holding potential and command potential program. Results The INCX in ventricular myocytes from the border zone of infarcted myocardium increased significantly at eight weeks after MI （0. 51 ± 0. 12 pA/pF vs 1.07± 0. 21 pA/pF, P 〈0.05）. β2-AR agonist increased INcx more strongly in myocytes from post- MI heart than in controls. β2-AR antagonist attenuated the rise of INCX, strongly in myocytes from post-MI heart than in controls, whereas β1-AR onist. Conclusion The regulation effects of β2-AR on INCX in myocytes AR had closer relationship with the genesis of malignant arrhythmia afte     

Changes of Plasma Levels of Brain Natriuretic Peptide in Patients With Chronic Heart Failure before and after Carvedilol Treatment

To investigate the changes of plasma brain natriuretic peptide (BNP) concentrations in patients with chronic heart failure (CHF) before and after carvedilol treatment. Methods Plasma BNP concentrations of patients with CHF (n=56) before and after carvedilol treatment and of normal controls (n=60) were measured with specific radioimmunoassay. Left ventricular ejection fraction of patients with CHF before and after carvedilol was measured with 99mTc gated cardiac blood pool scintigraphy. Results The results showed that plasma BNP concentrations of patients with CHF were significantly higher than that of normal controls [(222.65±78.52) ng·L-1 vs. (38.82±15.31) ng·L-1, P<0.01]. Plasma BNP concentrations had a significant negative correlation with left ventricular ejection fractions (r=-0.68,P<0.01). After three months treatment of carvedilol, plasma BNP concentrations fell to (79.65±69.52) ng·L-1(P<0.01), left ventricular ejection fractions increase from 34.41%±4.54% to 46.51%±5.38%(P<0.01). Conclusions These results indicate that plasma BNP concentrations are increased in patients with CHF, and markedly increased according to the severity of heart failure classified by NYHA classification. Carvedilol can markedly decrease plasma BNP concentrations and improve left ventricular function in patients with CHD.     

Effect and mechanism of Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia through connexin43(cx43)

Objective: To explore the effect and mechanism of angiotensin Ⅱ receptor blockers-Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. Methods: Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan+ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43(Cx43) mR NA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group(SO), myocardial infarction group(MI), Irbesartan group and MI+ Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorphology of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mR NA and protein level. Results: The intervention of Irbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia(P0.05), but in the presence of Irbesartan, the expression of Cx43 was increased compared with the ischemia group(P0.01). The results of WB assay showed the similar trend of change at mRNA level. There was the significant difference in the score of ventricular arerythmia between MI group and SO group(P0.01). The incidence of ventricular tachycardia or ventricular fibrillation was significantly increased compared with the one in SO group(P0.05). There was the significant difference in the overall score between MI+Irbesartan group and MI group(P0.05). The expression of Cx43 in the cardiac muscular tissue in MI group was significantly decreased(P0.01 vs SO group). But the expression of Cx43 was increased after the treatment with Irbesartan. Conclusions: Irbesartan can inhibit the injury of H9c2 cardiomyocytes and the decreased expression of Cx43 that are induced by the ischemic myocardial infarction. Irbesartan can also improve the reconstruction of Cx43 in rats with ischemic myocardium to inhibit the myocardial infarction-induced arrhythmias.     

Effects and mechanism of different doses of Xinfuli Granule on ventricular remodeling and myocardial fibrosis after acute myocardial infarction in rats

Background Recent clinical and experimental studies have confirmed the effects of Xinfuli Granule (XG), a compound Chinese medicine in the prevention and treatment of heart failure (HF). This study aimed to investigate the effects and the mechanisms of XG on ventricular reconstruction in rats with acute myocardial infarction (AMI). Methods Sprague-Dawley rats were subjected to left anterior descending branch ligation. The rats that survived 24 h were randomly assigned to 5 groups: medium-dose of XG group (MI+XGM), high-dose of XG group (MI+XGH), carvedilol group (MI+C), medium-dose of XG + carvedilol group (MI+C+XGM). Fourteen rats underwent identical surgical procedures without artery ligation, serving as sham controls. At 28 days, left ventricular weight to body weight (LVW/BW) and heart weight to body weight (HW/BW) were calculated; left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), left ventricular internal diameter at systole (LVIDS) were measured by ultrasound; HE staining, Masson staining, and Sirius red staining were used to assess the myocardial pathological and physiological changes as well as myocardial fibrosis area and non-infarct zone I/III collagen ratio. Expression of Smad3 were detected and analyzed by Western blot, immunohistochemistry and immunofluorescence. P-Smad3, Smad2 and Smad7 in the TGF-β/Smads signaling pathway were also analyzed by Western blot. Results The LVIDS (P < 0.01), HW/BW (P < 0.05), type I/III collagen ratio (P < 0.01) and myocardial collagen (P < 0.01) decreased significantly while the LVW/BW, LVFS (P < 0.05) increased significantly in MI+XGM group as compared with those in other groups. The expression of key signal molecules of the TGF-β/Smads signaling pathway, including Smad3, P-Smad3 and Smad2 protein were decreased while the expression of Smad7 increased in both XG and carvedilol treatment groups as compared to those of the MI group (all P < 0.01). Immunohistochemistry and immunofluorescence further confirmed the down-regulated Smad3 expression. Conclusion XG can improve ventricular reconstruction and inhibit myocardial fibrosis in rats with AMI by regulating TGF-β/Smads signaling pathway.     

Beneficial Effects of Delayed Opening the Infarct - related Artery on Late Phase Left Ventricular Function in Acute Anterior Myocardial Infarction

Objectives To assess the effect of delayed opening the infarct - related artery(IRA) by percutanous coronary intervention (PCI) on the late phase left ventricular function after acute anterior myocardial infarction. Methods 64 patients with initial Q -wave anterior myocardial infarction and the infarct- related arteries were total occluded conformed by angiogram at 2 to 14 days after onset were divided into successful PCI group and control group (not receiving PCI or the IRA not re - opened). 2 - DE was performed at early phase ( about 3 weeks) , 2 and 6months after onset of AMI respectively to detect the left ventricular function and left ventricular wall motion abnormality (VWMA). The total congestive heart failure events were recorded during 6 months follow-up. Results VWMA scores, left ventricular ejection fraction (LVEF), left ventricular end - diastolic and end-systolic volume indices (LVEDVI and LVDSVI)were similar in 2 groups at early phase and 2 months.There were no differences between early phase and 2months in each group too. VWMA scores and LVEF did not changed at 6 months in each group compared with the early phase and 2 months (P ＞ 0.05 ). But LVEDVI and LVESVI were significantly smaller in the successful PCI group than in the control group (P ＜0.01,P ＜ 0. 05 ). The congestive heart failure events were taken place in 19% of patients in control group compared with 2% in successful PCI group ( P ＞ 0.05 ).Conclusions Although the infarct size does not changed, delayed opening the IRA has beneficial effect to the late phase left ventricular dilatation after acute anterior myocardial infarction.     

Dynamic changes of α-AR,β1-AR and β2-AR expression during hepatic fibrogenesis

Objective To investigate the dynamic changes of α-AR,β1-AR and β2-AR expression in hepatic fibrosis.Methotis Rat hepatic fibrosis model was established by bile duct ligation(BDL).HE and Masson staining were used to determine hepatic fibrosis levels.Immunohistochemistry was applied to detect α-sooth muscle actin(α-SMA),a marker of hepatic stellate cell(HSC)activation;Western blot and realtime RT-PCR were used to measure the dynamic changes of α-AR,β1-AR,β2-AR expression on protein and mRNA levels.respectively,during the development of hepatic fibrosis.Results(1)HE and Masson trichrome staining showed that the liver fibrosis modeIs were established successfully.(2)At 1,2,3,4 wk after BDL,α-SMA positive area density of the model group(10.58%±1.75%,24.1 4%±2.02%,29.74%±2.59%,34.28%±2.01%)was significantly higher than that of the sham operation group (4.12%±1.51%),P＜0.01.(3)The expression of α-AR,β1-AR,β2-AR protein and mRNA was increased with the development of the hepatic fibrosis(P＜0.05).(4)α-SMA expression Was positively associated with α-AR,β1-AR,β2-AR,r values were 0.564,0.753 and 0.606,respectively.Conclusions The expression of α-SMA is increased dramatically during the fibrosis,and is positively associated with the expression of α-AR,β1-AR and β2-AR.     

Changes of Plasma Levels of Brain With Chronic Heart Failure before Natriuretic Peptide in Patients and after Carvedilol Treatment

Objectives To investigate the changes of plasma brain natriuretic peptide （BNP） concentrations in patients with chronic heart failure （CHF） before and after carvedilol treatment. Methods Plasma BNP concentrations of patients with CHF （n = 56） before and after carvedilol treatment and of normal controls （n = 60） were measured with specific radioimmunoassay. Left ventricular ejection fraction of patients with CHF before and after carvedilol was measured with 99mTc gated cardiac blood pool scintigraphy. Results The results showed that plasma BNP concentrations of patients with CHF were significantly higher than that of normal controls [ （222. 65 ± 78.52） ng·L^-1 vs. （38.82 ± 15.31 ） ng·L^-1 , P 〈 0. 01 1. Plasma BNP concentrations had a significant negative correlation with left ventricular ejection fractions （r=-0. 68 ,P 〈 0. 01 ）. After three months treatment of carvedilol, plasma BNP concentrations fell to （79. 65 ±69.52 ）ng·L^-1 （P 〈 0. 01 ）, left ventricular ejection fractions increase from 34. 41% ± 4. 54% to 46. 51% ± 5.38 % （P 〈 0. 01 ）. Conclusions These results indicate that plasma BNP concentrations are increased in patients with CHF, and markedly increased according to the severity of heart failure classified by NYHA classification. Carvedilol can markedly decrease plasma BNP concentrations and improve left ventricular function in patients with CHD.     

Effect of carvedilol on attenuating the acute myocardial infarction-induced myocardial fibrosis in rats

Carvedilol,nonselective β-adrenoreceptor antagonist,was showed protective effects against acute myocardial infarction(AMI)-induced myocardial injury,however,the mechanisms underlying the antifibrosis effect of carvedilol has not been well known.The aim of the present study was to investigate the potential mechanism for the anti-fibrosis effect of carvedilol against AMI-induced myocardial fibrosis in rats.Methods Male SD rats were randomized into the sham group,LAD surgery-AMI model group,AMI plus low dose of carvedilol treatment group(1 mg /kg per day,CAR-L),AMI plus medium dose of carvedilol treatment group(5 mg /kg per day,CAR-M) and AMI plus high dose of carvedilol treatment group(10 mg /kg per day,CAR-H).The passage 3 neonatal SD rat cardiac fibroblasts were used for hypoxia /normoxia(2 h /4 h) treatment in the presence of carvedilol(0,1,2 and 4 μM).Results Cardiac remodeling and impaired heart function were observed after 14-week LAD surgery treatment,however,and the cardiac remodeling and decreased ejection fraction(EF%) and fractional shortening(FS%) were efficiently rescued in the CAR-M and CAR-H groups.The up-regulated expressions of Col1a1,Col3a1 and α-SMA at mRNA and protein levels were significantly reduced in the CAR-M and CAR-H groups.The in vitro study showed that Col1a1,Col3a1 and αSMA expressions at both mRNA and protein levels were down-regulated by carvedilol in rat cardiac fibroblasts in a dose-dependent manner.Smad3 inhibitors,SIS-3 and naringenin,could efficiently decrease Col1a1,Col3a1 and α-SMA expressions in rat cardiac fibroblasts.Smad3 was shown significantly inactivated in carvedilol-treated rat cardiac fibroblasts.Conclusion Carvedilol negatively regulates Smad3 signal pathway and inhibits extracellular matrix related Col1a1,Col3a1 and α-SMA expressions,contributing to the anti-fibrosis effect of carvedilol against AMI-induced myocardial fibrosis in rats.     

Effect of Losartan on the Cardiac and Renal Function in Patients With Chronic Heart Failure

Objectives To explore the effect of losartan on cardiac and renal function in patients with chronic heart failure (CHF). Methods Sixty-five patients with CHF were divided into two groups using a randomized, control and single blind method: losartan group (n=30) and convention group (n=35), with a treatment course of 8 weeks for both groups. The concentrations of cystatin C (cys C) in serum, microamount albumin (MA) in urine were measured by immunoturbidimetry. The concentration of aquaporin-2(AQP-2)was determined by enzyme-linked-immunosorbent assay (ELISA) and the heart contractile function was measured by echocardiography before and after treatment respectively. Results Comparing with routine treatment group, left ventricular end-diastolic dimension (LVEDd) decreased significantly, while left ventricular ejection fraction(LVEF)and left ventricular fractional shortening (LVFS) increased significantly in losartan group. The levels of cys C in serum and MA, AQP-2 in urine were significantly lower in losartan group than in routine treatment group. Conclusion Losartan can improve cardiac and renal function in patients with CHF.     

Is it time to replace propranolol with carvedilol for portal hypertension?

Beta-adrenergic receptor antagonists(β-blockers) have been well established for use in portal hypertension for more than three decades. Different Non-selective β-blockers like propranolol, nadolol, timolol, atenolol, metoprolol and carvedilol have been in clinical practice in patients with cirrhosis. Carvedilol has proven 2-4 times more potent than propranolol as a beta-receptor blocker in trials conducted testing its efficacy for heart failure. Whether the same effect extends to its potency in the reduction of portal venous pressures is a topic of on-going debate. The aim of this review is to compare the hemodynamic and clinical effects of carvedilol with propranolol, and attempt assess whether carvedilol can be used instead of propranolol in patients with cirrhosis. Carvedilol is a promising agent among the beta blockers of recent time that has shown significant effects in portal hypertension hemodynamics. It has also demonstrated an effective profile in its clinical application specifically for the prevention of variceal bleeding. Carvedilol has more potent desired physiological effects when compared to Propranolol. However, it is uncertain at the present juncture whether the improvement in hemodynamics also translates into a decreased rate of disease progression and complications when compared to propranolol. Currently Carvedilol shows promise as a therapy for portal hypertension but more clinical trials need to be carried out before we can consider it as a superior option and a replacement for propranolol.     

Influence of calcium preconditioning and streptomycin on ventricular dilation-induced arrhythmias in isolated rat hearts

Objective To investigate the mechanism of ventricular dilation-induced arrhythmias by dilating isolated rat hearts. Methods Isolated rat hearts were perfused by Langerdorff method. After equilibration,80 hearts were randomly divided into four groups as follows:(1) control group(n=20) ,(2) Ca2 preconditioning(CPC) group(n=20) ,(3) streptomycin group(n=20) ,and(4) CPC streptomycin group(n=20) . A latex balloon which can be filled with fluid was anchored in the left ventricle through the left atrium and mitral valve. Epicardial ECG of the left ventricle,left ventricular pressure,coronary flow and heart rate were recorded before and during ventricular dilation by injecting fluid into the latex balloon. The rate and duration of ventricular dilation-induced arrhythmias were recorded. Results Under the same increase in ventricular end-diastolic pressure made by inflation of the balloon,the rate of arrhythmias was 100% and duration of arrhythmias was 2. 56±0.46s in the control group. Both the rates of premature ventricular beat(90%) and ventricular tachycardia 70%) were high. Compared with the control group,the total rate(60%) of arrhythmias was lower,and duration(1.67±0.61s) of arrhythmias was shorter in the CPC group. Both the rates of premature ventricular beat(60%) and ventricular tachycardia(40%) were low comparatively. The rate of arrhythmias(45%) was lower and duration(1.64±0.42s) of arrhythmias was shorter,and the rates of premature ventricular beat(30%) or ventricular tachycardia(35%) were lower in the streptomycin group than in the control one. The least ventricular dilation-induced arrhythmias occurred in the CPC streptomycin group. The rate of arrhythmias(10%) was the lowest and duration(1.01±0.37s) of arrhythmias was the shortest;both the rates of premature ventricular beat(5%) and ventricular tachycardia(10%) were the lowest. Conclusions Ventricular dilation may induce arrhythmias in isolated rat hearts. Stretch-activated ion channel and the increase in [Ca2 ]i are supposed to play important roles in the pathological mechanism.     

老龄小鼠心肌梗死后wnt信号通路表达的变化及与心脏破裂的关系

Objective To observe the association between wnt signal pathway and post infarction left ventricular remedeling/rupture in mice with various ages. Methods Three months-old (young group, n=116) and 18 months-old (aged group, n = 116) male C57/BL mice were studied. Seventy mice underwent ligation of left coronary artery, 10 sham-operation and echocardiography and hemodynamics were performed 7 d post-infarction, 36 infarcted mice were used for detecting expression of dvl-1, β-catenin and connexin 43 in left ventricular (LV) myocardium and infarction region at 3 d, 7 d, 14 d post infarction (n = 12 each). Results Incidence of cardiac rupture was significantly higher in aged mice than in young mice (36.7% vs. 16.7% ,P <0.05) and degree of LV dilation and contractile dysfunction was significantly severer in aged mice than those in young mice post infarction. Expression of dvl-1, β-catenin in left ventricle was upregulated in MI group compared with sham group(P <0.05), expression of dvl-1 and β-catenin in infarction region in MI 3d group in aged mice was significantly downregulated than in young mice (P < 0.05). Expression of connexin 43 is 2.15 fold higher in young sham mice than in aged sham mice (P < 0.05) and decreased significantly post infarction (P < 0.05). Expression of connexin 43 in infarction region in mice 3 d and 14 d post infarction was significantly lower in aged mice than in respective young mice(all P < 0.05). Conclusion Reductant activation of wnt signal pathway post infarction in aged mice might be responsible for increased incidence of cardiac mpture and aggravated remodeling.     

Effect of captopril on myocardial energy metabolism in chronic pressure overload rats

Objective To investigate the effects of captopril on cardiac function and levels of energy-rich phosphates in pressure overload induced left ventricular hypertrophy rats. Methods One hundred and twenty SD rats were randomly divided into three groups： sham operation group （SH group, n=40）,coarctation of abdominal aorta group （CAA group, n=40） and captopril treatment lmg~ 100g1 ~ d-1） group （CAP group, n=40）. Left ventricular end-diastolic pressure （LVEDP）, left venh-icular mass index （LVMI）, levels of energy-rich phosphates and morphological changes of the myocardial mitochondria were compared at the 62 and 82 week after operation. Results At 62 week, in CAA group, LVMI and LVEDP were increased and _ dp/dtmax was decreased, while ATP and ADP were decreased and AMP was increased （P〈0.01）. These changes were much obvious at 8th week （P〈0.01）. Compared with those of CAA group, the parameters of heart function and energy-rich phosphates （ATP, ADP, AMP, TAN） in CAP group were improved significantly（P〈0.01） at the 6th and 8th week. In CAP group, the parameters of heart function and energy-rich phosphates （ADP, AMP, TAN） were much better at 8~ week than those at 6th week. The morphological change of mitochondria was less in CAP group than that in CAA group. Conclusion Captopril significantly improves myocardial energy metabolism in pressure overload rats and protects the function of myocardial mitochondria     

Effects of ivabradine on cardiomyocyte apoptosis after rabbit acute myocardial infarction

Epidemiological studies have confirmed that high heart rate means high risk to patients with coronary heart disease.The research investigates the viability and the effects of ivabradine versus atenolol in early phases of acute myocardial infarction(AMI) on rabbits after 28 days of follow-up.The ratio of bcl-2 protein to Bax protein determines survival or death after an apoptotic stimulus.We forecast that bcl-2 or Bax expression places a premium on ischemia and that it may be linked to myocyte death in human hearts.Methods Forty-three New Zealand white rabbits(male or female) were used to build AMI mode through ligating left anterior descending coronary artery.Survived rabbis were randomly divided into four groups:group S,group M,group A and group I.Drugs were provided 12 hours post myocardial infarction induction.The myocardium in ischemic necrosis tissue was sampled 28 days post dose.AI and bcl-2 /bax protein expression were detected.The heart rates of rabbits before operation and 28 days after operation were recorded by electrocardiography and analyzed.Results On 28th day post-operation,the heart rate of rabbits in groups A and I significantly became slower compared with that in group M(P < 0.01).The proportion of myocardial cell apoptosis in groups I and A was significantly lower than that in group M and higher than that in group S(P < 0.01) on 28th day post-operation On 28th day post-operation,compared with group M,the level of Bcl2 protein in rabbits of groups I and A significantly increased(P < 0.01),the level of Bax protein significantly decreased(P < 0.01),and No statistical difference was found between group I and group A.Conclusion reating myocardial infarction rabbits with ivabradine for 28 days could effectively reduce the incidence of myocardial cell apoptosis and increase bcl-2 /bax ratio.     

Infuences of Previous Angina Pectoris on Coronary Collateral Circulation and Left Ventricular Function in Patients with Acute Myocardial Infarction

Objective To investigate the influences of previous angina pectoris on coronary collateral circulation and left ventricular function in patients with acute myocardial infarction. Methods 307 patients with a first episode acute myocardial infarction underwent selective coronary angiography and left ventriculography. The relation of previous angina pectoris to coronary collateral circulation, peak creatine kinase and left ventricular function were analyzed. Results ①In the 307 patients, there were 192 (62. 5 % ) with previous angina [PA (+) group] and 115 (37. 5 % ) without [PA (-) group].②The peak creatine kinase (CK) and CK MB were significantly higher in PA (-) group than in PA (+) group (P<0. 05 for both comparisons) . ③ Collateral circulation to infarct-related artery was more likely to be present in PA (+) group than in PA (-) group (P<0. 05) .④The left ventricular ejection fraction was significantly increased, and the left ventricular wall motion Cortina score decreased, in PA (+) group than in     

Mechanism of TLR-4/NF-κB pathway in myocardial ischemia reperfusion injury of mouse

Objective: To detect the expression of Toll-like receptor 4(TLR-4) and NF-κB and to discuss the mechanism of TLR-4/NF-κB pathway in the myocardial ischemia reperfusion injury of mouse. Methods: TLR-4 mutant mice and wild homozygous mice were divided into the model group and sham group. Mice in the model group were given the ligation of left anterior descending coronary artery for the modeling, while mice in the sham group were not given the ligation after threading. The cardiac muscle tissues were collected for the morphological observation. The immuno histochemistry was employed to detect the expression of NF-κB, Western blot was used to detect the expression of TLR-4 and ELISA to detect the expression of serum inflammatory factors. Results: The expression of NF-κB in TLR-4 null mice after the myocardial ischemia reperfusion was significantly lower than that in wild homozygous mice. For the model group and sham group, the expression of TLR-4 in wild homozygous mice was all significantly higher than that in TLR-4 null mice, while the expression of TLR-4 in TLR-4 null mice in the model group was significantly higher than that in sham group, with the statistical difference(P0.05). The expression of inflammatory factors in TLR-4 null mice and wild homozygous mice in the model group was significantly higher than that in sham group. The expression of all factors in group A with TLR-4 null was significantly lower than that in group B with wild homozygous type, with the statistical difference(P0.05). Conclusions: TLR-4/NF-κB pathway is closely related to the myocardial ischemia reperfusion injury, which plays its role through the release of inflammatory cytokines.