Correlation between growth differentiation factor-15 and collagen metabolism indicators in patients with myocardial infarction and heart failure

BackgroundGrowth differentiation factor （GDF）-15, a divergent member of the transforming growth factor beta super-family does appear to be up-regulated in response to experimental pressure overload and progression of heart failure （HF）. HF frequently develops after myocardial infarction （MI）, contributing to worse outcome. The aim of this study is to assess the correlation between GDF-15 levels and markers related to collagen turnover in different stages of HF.MethodsThe study consists of a cohort of 179 patients, including stable angina pectoris patients （AP group,n= 50）, old MI patients without HF （OMI group,n = 56）, old MI patients with HF （OMI-HF group,n= 38） and normal Control group （n = 35）. Both indicators reflecting the synthesis and degradation rates of collagen including precollagen I N-terminal peptide （PINP）, type I collagen carboxy-terminal peptide （ICTP）, precollagen III N-terminal peptide （PIIINP） and GDF-15 were measured using an enzyme-linked inmunosorbent assay.ResultsThe plasma GDF-15 level was higher in OMI-HF group （1373.4 ± 275.4 ng/L） than OMI group （1036.1 ± 248.6 ng/L）, AP group （784.6 ± 222.4 ng/L） and Control group （483.8 ± 186.4 ng/L） （P〈 0.001）. The indi-cators of collagen turnover （ICTP, PINP, PIIINP） all increased in the OMI-HF group compared with Control group （3.03 ± 1.02μg/Lvs. 2.08 ± 0.95μg/L, 22.2 ± 6.6μg/Lvs. 16.7 ± 5.1μg/L and 13.2 ± 7.9μg/Lvs. 6.4 ± 2.1μg/L, respectively;P〈 0.01）. GDF-15 positively cor-related with ICTP and PIIINP （r = 0.302,P〈 0.001 andr= 0.206,P= 0.006, respectively）. GDF-15 positively correlated to the echocardio-graphic diastolic indicators E/Em and left atrial pressure （r= 0.349 and r= 0.358, respectively;P〈 0.01）, and inversely correlated to the systolic indicators left ventricular ejection fraction and the average of peak systolic myocardial velocities （Sm） （r=-0.623 and r=-0.365, respectively;P〈 0.01）.ConclusionPlasma GDF-15 is associated with the indicators of type I and III collagen turnover.

DIETARY MAGNESIUM DEFICIENCY INCREASES LEVELS AND FUNCTION OF Giα IN THE RAT HEART AFTER MYOCARDIAL INFARCTION

Magnesium(Mg) is crucial for the function of G proteins which play important roles in mediating the inotropic effects of β adrenergic agonists in the heart and are alteredin heart failure.This study was performed to determine whether or not dietary Mg deficiency alters functional activity and levels of the two major ventricular G proteins, Gia and Gsa in the heart after myocardial infarction(MI).Six week old rats were fed a Mg adequate or deficient diet for 6 weeks.At the end of week 3,MI was induced by coronary artery ligation.A sham operation was performed as control.After surgery,surviving animals were maintained on their assigned diets for another 3 weeks.Then,cardiac function was measured.Severe hypomagnesemia and increased plasma catecholamine level were observed in all animals fed the Mg deficient diet.A significant reduction of ruyocardial Mg concentration accompanied by elevated plasma and myocardial calcium concentrations was observed in MI animals with existing Mg deficiency vs.animals fed the Mg adequate diet.Cardiac function was impaired in MI rats and further reduced in MI rats with existing Mg deficiency. Gia level was not altered by either Mg deficiency or MI alone,but was dramatically elevated in animals with combined Mg deficiency and MI (9. 9±0.7 arbitrary unit.mg-1 protein) as compared to MI alone (5.8±0. 6,P<0.05 )and Mg deficiency alone(6.1± 0.8,P<0.05 ). Gsa level did not differ between groups.Bacal,GppNHp-and forskolin-but not fluoride-, stimulated adenylyl cyclase activity was signifcantly reduced in MI animals with existing Mg deficiency indicating increased functional activity of Gia.The findings suggest that dietary Mg deficiency increases the expression and functional ac tivity of Gia in the heart after MI, while levels and function of Gsa are not compromised during dietary Mg deficiency either with or without MI.

The influence of tirofiban on the troponin, brain natriuretic peptide, heart function in patients with Acute Myocardial Infarction after PCI

Objective:To observe the influence of tirofiban on the troponin, brain natriuretic peptide, heart function in patients with Acute Myocardial Infarction after PCI and provide scientific basis for treatment of acute myocardial infarction.Methods:A total of 100 cases of hypertensive cerebral hemorrhage patients in our hospital were selected and randomly divided into 2 groups: the control group (50 cases) and the observation group (50 cases). The conventional treatment of PCI was performed on both groups. Tirofiban injection was given to the observation group on the basis of conventional treatment. cTnI, BNP and echocardiography parameters (LVEF, LVEDD, LVESD) were detected before and after treatment.Results:The comparison of cTnI in the two groups before operation was not statistically significant. cTnI in the 2 groups increased 12 h and 24 h after operation. But the cTnI in observation group (0.10±0.23) ng/mL decreased more significantly than that in control group (0.24±0.31) ng/mL, the difference was considered to be statistically significant. The comparison of BNP in the two groups before operation was not statistically significant. BNP in the 2 groups decreased obviously 7 d and 30 d after operation. BNP in observation group decreased more significantly than that in control group and the difference was considered to be statistically significant LVEF in the observation group increased significantly compared with that in control group 7 d after operation. The comparison of LVEDD, LVESD were not considered to be statistically significant. LVEDD and LVESD in the observation group were lower than that in control group obviously 30 d after operation. While the LVEF in the observation group was still higher than that in the control group. The comparsion was considered to be statistically significant.Conclusion:Tirofiban can improve the troponin, brain natriuretic peptide, heart function in patients with Acute Myocardial Infarction after PCI. It can also decrease the heart injury as well as helping the recovery of heart function.

Effect of recombinant human brain natriuretic peptide on serum inflammatory factors, neuroendocrine hormones and cardiac function in patients with acute myocardial infarction complicated with heart failure

Objective:To investigate the effect of recombinant human brain natriuretic peptide (BNP) on inflammatory factors, neuroendocrine hormones and cardiac function indexes in patients with acute myocardial infarction complicated with heart failure.Methods:A total of91 cases of acute myocardial infarction with heart failure patients were divided into the control group (n=44) and observation group (n=47) according to the random data table, two groups of patients were given conventional treatment, based on this, the control group was given intravenous infusion of Nitroglycerin Injection treatment, the observation group received intravenous injection of recombinant human brain natriuretic peptide treatment, compared serum inflammatory factors, neuroendocrine hormone and cardiac function and other indexes of two groups before and after treatment.Results: there was no significant difference between the two groups before treatment. After treatment, the levels of TNF-α, hs-CRP, IL-6, MCP-1, LVESD and LVEDD in the two groups were significantly lower than those within the group before treatment, and the observation group was significantly lower than the control group;The two groups after treatment LVEF levels were significantly higher than those in the group before treatment, and the observation group was significantly higher than that of control group;the observation group after treatment PRA, Ang II and ALD and NE levels were significantly lower than those before treatment, and was significantly lower than the control group after treatment, the difference was significant, PRA, Ang, ALD and NE levels of control group before and after the treatment was no significant difference.Conclusion:recombinant human brain natriuretic peptide in the treatment of acute myocardial infarction with heart failure can effectively reduce the serum inflammatory factors and neuroendocrine hormone levels, improve heart function, and have a certain clinical value.

Granulocyte-macrophage colony stimulating factor improves cardiac function in rabbits following myocardial infarction

Objective: To investigate the therapeutic potency of recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in a rabbit myocardial infarction model. Methods: A myocardial infarction was created by the ligation of the major ventricular branch of the left coronary artery in rabbits. After myocardial infarction, the animals were randomly assigned to GM-CSF treatment group, untreated groups and sham-operated group. The rabbits of the treated group were injected into GM-CSF by subcutaneous administration, 10 μg/kg/day, once a day for 5 days. The untreated and sham-operated group received a equal saline in the same manner as treated group. Six weeks later echocardiography and haemodynamic assessment were undertaken to assesse cardiac function. The size of the infarct region of the heart were also studied. Results: The untreated group exhibited significant higher left ventricle end-diastolic pressure, higher central venous pressure, and with significant lower mean blood pressure, lower peak first derivative of left ventricle pressure (dP/dt) than the sham group. Also, Rabbits in untreated group display significant systolic dysfunction shown by the decreased ejection fraction, diastolic dysfunction shown by increasing in the ratio of E wave to A wave (E/A), and display left ventricle enlargement. However, GS-CSF singnificantly prevented heart dysfunction, left ventricle enlargement, and reduced infarct size in treatment group. Conclusion: Administration GM-CSF after cardiac infarction can improve heart function. These findings indicate the technique may be a novel and simple therapeutic method for ischemic myocardium.

Dapagliflozin in heart failure and type 2 diabetes:Efficacy,cardiac and renal effects,safety

BACKGROUND Heart failure(HF),especially HF with reduced ejection fraction(HFrEF),presents complex challenges,particularly in the aging population where it often coexists with type 2 diabetes mellitus(T2DM).AIM To analyze the effect of dapagliflozin treatment on cardiac,renal function,and safety in patients with HFrEF combined with T2DM.METHODS Patients with T2DM complicated with HFrEF who underwent treatment in our hospital from February 2018 to March 2023 were retrospectively analyzed as the subjects of this study.The propensity score matching method was used,and a total of 102 eligible samples were scaled.The clinical efficacy of the two groups was evaluated at the end of the treatment,comparing the results of blood glucose,insulin,cardiac function,markers of myocardial injury,renal function indexes,and 6-min walk test(6MWT)before and after the treatment.We compared the occurrence of adverse effects on the treatment process of the two groups of patients.The incidence of adverse outcomes in patients within six months of treatment was counted.RESULTS The overall clinical efficacy rate of patients in the study group was significantly higher than that of patients in the control group(P=0.013).After treatment,the pancreatic beta-cell function index,left ventricular ejection fraction,and glomerular filtration rate of patients in the study group were significantly higher than control group(P<0.001),while their fasting plasma glucose,2-h postprandial glucose,glycosylated hemoglobin,insulin resistance index,left ventricular end-systolic diameter,left ventricular end-diastolic diameter,cardiac troponin I,creatine kinase-MB,N-terminal pro b-type natriuretic peptide,serum creatinine,and blood urea nitrogen were significantly lower than those of the control group.After treatment,patients in the study group had a significantly higher 6MWT than those in the control group(P<0.001).Hypoglycemic reaction(P=0.647),urinary tract infection(P=0.558),gastrointestinal adverse effect(P=0.307),respiratory disturbance(P=0.558),and angioedema(P=0.647)were not statistically different.There was no significant difference between the incidence of adverse outcomes between the two groups(P=0.250).CONCLUSION Dapagliflozin significantly enhances clinical efficacy,cardiac and renal function,and ambulatory capacity in patients with HFrEF and T2DM without an increased risk of adverse effects or outcomes.

DYNAMIC CHANGES IN Giα2 LEVELS IN THE RAT HEART ASSOCIATED WITH IMPAIRED CARDIACFUNCTION FOLLOWING ACUTE MYOCARDIAL INFA RCTION

Changes in the functional activity and levels of Gsa and Gia in heart failure have been studied predominantly in the end-stage failing heart.The objective of this study was to determine if levels and function of Gsa and Gia2 in rat hearts change over time following acute myocar(lial infarction (MI) and if so,whether the changes in G proteins are associated with changes in heart function.As compared with sham-operated controls, Giα2, level of MI rats did not change at day l,increased by 64% at day 3 (P<0.01) and 55% at day 9 (P< 0.05)accompanied by reduced adenylyl cyclase activity,and returned to control by day 21. By contrast,Gsa level did not change at any time. Cardiac function in MI animals was markedly impaired at days 1,3 and 9 as evidenced by substantial elevation in LVEDP and reduction in +and -dp/dtmax,and partially restored at day 21. The increased Gia2level in MI rats at days 3 and 9 correlated positively to LVEDP(P< 0.05), and negatively to +and -dp/dtmax (p < 0. 01).The results show a three phase dynamic pattern in Gia2 level following acute MI:a lag phase, an increased expression phase associated with marked impairment of heart function,and a late phase in which the expression retums to control level accompanied by partially restored cardlac function.The results suggest that ② in G protein-mediated pathways,cardiac myocytes respond to MI Via regulating the gene expression of the inhibitory pathway, and ② up-regulation of Gia2 levels is related to the severity of impairment in cardiac function.

Effect of perindopril on the myocardial energy consumption in patients with heart failure after myocardial infarction

Objective:To explore the clinical efficacy of perinodopril in the treatment of heart failure in patients after myocardial infarction and effect on the myocardial energy consumption. Methods:A total of 87 patients with heart failure after myocardial infarction who were admitted in our hospital from August, 2014 to October, 2015 were included in the study and divided into the routine dose group (n=43, perinodopril 4 mg/d) and high dose group (n=44, perinodopril 8 mg/d) according to the long-term oral dose. All the patients were given perinodopril, continuously for 6 months. The changes of blood pressure and serum biochemical indicators before and after treatment in the two groups were compared. The changes of cardiac function indicators and myocardial energy consumption indicators before and after treatment in the two groups were compared. 6MWT 6 months and 1 year after treatment in the two groups was calculated.Results: The plasma BNP and H-FABP levels, LVEDD, LVESD, MEE, and cESS after treatment in the two groups were significantly reduced when compared with before treatment, and those in the high dose group were significantly lower than those in the low dose group. LVEF and FS after treatment in the two groups were significantly increased, and those in the high dose group were significantly greater than those in the routine dose group. The seurm potassium level after treatment in the high dose group was significantly elevated when compared with before treatment, but was not significantly different from that in the routine dose group. SBP, DBP, and Scr levels after treatment in the two groups were not significantly changed. 6MWT 6 months and 1 year after treatment in the high dose group was significantly greater than that in the routine dose group.Conclusions: Perinodopril in a high dose can significantly reduce the plasma BNP and H-FABP levels in patients with heart failure after myocardial infarction, inhibit the ventricular remodeling, promote the recovery of systolic function, reduce the myocardial energy consumption, and will not affect the blood pressure, serum potassium, and renal function, with efficacy significantly superior to that in a low dose;moreover, it has a certain safety.

Inhibition of TGF-β1 by eNOS gene transfer provides cardiac protection after myocardial infarction

Objective： Endothelial nitric oxide synthase （eNOS） and nitric oxide （NO） have been implicated in protection against myocardial ischemia injury. This study was designed to explore a new method of therapy for myocardial injury by eNOS gene transfection. Methods： A rat model of myocardial infarction （MI） was established by left anterior descending （LAD） coronary artery ligation, eNOS gene in an adenovirus vector was delivered locally into the rat heart and hemodynamic parameters were examined after 3 weeks, Matrix metalloproteinase-2 and 9 （MMP-2, MMP-9） mRNA were measured by reverse transcription polymerase chain reaction （RT-PCR）, and the protein levels of eNOS, caspase-3, and transforming grouth factor 131 （TGF-131） were determined by western blot assay. Results： eNOS gene transfer significantly reduced cardiomyocyte apoptosis and improved cardiac function. In addition, eNOS significantly reduced the mRNA levels of MMP-2 and MMP-9. In the eNOS gene transfected group, the activation of caspase-3 and TGF-β1 were decreased. However, the protection was reversed by administration of the NOS inhibitor, N（o））-nitro-l-arginine methyl ester （L-NAME）. Conclusion： These results demonstrate that the eNOS provides cardiac protection after myocardial infarction injury through inhibition of cardiac apoptosis and collagen deposition, and suppression of TGF-β1.

Not all arrestins are created equal: Therapeutic implications of the functional diversity of the β-arrestins in the heart

The two ubiquitous, outside the retina, G protein-coupled receptor(GPCR)adapter proteins, β-arrestin-1 and-2(also known as arrestin-2 and-3,respectively), have three major functions in cells: GPCR desensitization, i.e.,receptor decoupling from G-proteins; GPCR internalization via clathrin-coated pits; and signal transduction independently of or in parallel to G-proteins. Bothβ-arrestins are expressed in the heart and regulate a large number of cardiac GPCRs. The latter constitute the single most commonly targeted receptor class by Food and Drug Administration-approved cardiovascular drugs, with about onethird of all currently used in the clinic medications affecting GPCR function.Since β-arrestin-1 and-2 play important roles in signaling and function of several GPCRs, in particular of adrenergic receptors and angiotensin II type 1 receptors,in cardiac myocytes, they have been a major focus of cardiac biology research in recent years. Perhaps the most significant realization coming out of their studies is that these two GPCR adapter proteins, initially thought of as functionally interchangeable, actually exert diametrically opposite effects in the mammalian myocardium. Specifically, the most abundant of the two β-arrestin-1 exerts overall detrimental effects on the heart, such as negative inotropy and promotion of adverse remodeling post-myocardial infarction(MI). In contrast, β-arrestin-2 is overall beneficial for the myocardium, as it has anti-apoptotic and antiinflammatory effects that result in attenuation of post-MI adverse remodeling,while promoting cardiac contractile function. Thus, design of novel cardiac GPCRligands that preferentially activate β-arrestin-2 over β-arrestin-1 has the potential of generating novel cardiovascular therapeutics for heart failure and other heart diseases.

Efficacy and long-term evaluation of intramyocardial injection of autologous CD34-enriched PBMSC in old myocardial infarction

Aims: We have shown that autologous transplant of CD34+-enriched peripheral-blood mononuclear cells (PBMSC) could restore depressed myocardial function, and sustain adequate myocardial function 12 months after surgery in patients with old (>one year-old) myocardial infarction. Our aim is to report the long-term morbidity and mortality efficacy of this procedure. Methods and results: Seventy patients with an old anteroseptal myocardial infarction were followed for 2 to 7 years, 35 had a revascularization procedure and received an intra-myocardial injection of autologous CD34+-enriched PBMSC (8 × 108 mononuclear cells/ml including 3 × 107 CD34+ cells/ml)(Group A). Group B patients only had the revascularization. Abnormal pre-surgical values of LVEF (33.2% ± 4.8%), LVDV (178 ± 13.7 ml), LVSV (120 ± 16 m), LVDD (58.9 ± 3.84 mm), E and A waves without contractility in infarction area in group A patients improved to approximate normal values (50% ± 3% for LVEF;90 ± 9.3 ml for LVDV;80 ± 9.9 ml for LVSV;55.3 ± 3 mm for LVDD;5.2 ± 0.5 cm/s for E wave and 4.18 ± 0.3 cm/s for A wave) 1 year after the procedure and have remained unaltered for all the follow-up period. All the patients remain alive. Only seven patients have been readmitted to the hospital for non-myocardial related events. Group B only 11 patients continued alive to 5 years after surgery and LEVF never increased more than 6%, all of them with many hospitalizations (n ≥ 10) by heart failure events. Conclusion: Intramyocardial injection of CD34+ highly enriched PBSC represent an encouraging alternative for patients with severely scarred and dysfunctional myocardium.

老年女性急性心肌梗死致心力衰竭的临床特征和危险因素

目的探讨老年女性急性心肌梗死后心力衰竭的临床特点、危险因素,为临床诊治提供参考。方法回顾性分析北京市顺义区医院心血管内科2021年1—12月收治的80例老年急性心肌梗死患者(>60岁)的临床资料,按照性别进行分组后,对比2组临床特点:年龄、就诊时间、心功能分级、心肌酶、B型钠尿肽(N terminal pro B type natriuretic peptide,NT-proBNP)、多支病变比例等,并对心肌梗死患者心力衰竭的相关危险因素进行分析。结果老年女性发病年龄、病程、心梗后心衰发生率,就诊时间高于老年男性(t=5.235、4.644、8.876、14.755,P<0.05),老年女性心功能分级、TnⅠ、NT-proBNP高于老年男性(t=2.330、16.361,P<20.05),老年女性多支病变比例高于老年男性(χ=6.573,P<0.05)。老年女性急性心肌梗死患者发生心力衰竭的主要危险因素为冠心病家族史、高血压、糖尿病、高脂血症(P<0.05)。结论老年女性急性心肌梗死患者发生心力衰竭的危险性高于老年男性,合并冠心病家族史、高血压、糖尿病、高脂血症的患者发生心力衰竭的风险明显增加。

藏红花素对心肌梗死后心力衰竭大鼠心功能和心肌纤维化的影响

目的探讨藏红花素对心肌梗死后心力衰竭(心衰)大鼠心功能和心肌纤维化的影响及可能机制。方法采用结扎左冠状动脉(冠脉)前降支的方法构建心肌梗死后心衰大鼠模型,取80只成模大鼠随机分为模型组、卡托普利(10 mg/kg)组和藏红花素低剂量组(20 mg/kg)、中剂量组(40 mg/kg)、高剂量组(80 mg/kg),每组各16只;另取16只大鼠设为假手术组。造模完成后,各组分别灌胃给药,1/d。4周后,通过超声影像检测心功能指标[左室射血分数(LVEF)、左室短轴缩短分数(LVFS)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)],ELISA法检测血清心肌肌钙蛋白T(cTnT)、血管紧张素Ⅱ(AngⅡ)、脑钠肽(BNP)、醛固酮(ALD)含量,TTC染色法计算心肌梗死面积,计算左室心肌肥厚指数(LVHI),Masson染色观察心肌组织纤维化状况,ELISA法检测心肌组织白细胞介素-1β(IL-1β)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)含量,Western blot法检测Toll样受体4(TLR4)、核因子-κB p65(NF-κB p65)、转化生长因子-β1(TGF-β1)、Ⅰ型胶原(Collagen-Ⅰ)、Collagen-Ⅲ蛋白表达。结果与模型组比较,卡托普利组和藏红花素中、高剂量组大鼠LVEF和LVFS明显升高,LVEDD和LVESD明显降低(P<0.05);血清cTnT、AngⅡ、BNP、ALD含量和心肌梗死面积、LVHI明显降低(P<0.05);心肌组织纤维化状况明显改善,胶原容积分数(CVF)明显降低(P<0.05);心肌组织IL-1β、IL-8、TNF-α含量和TLR4、NF-κB p65、TGF-β1、Collagen-Ⅰ、Collagen-Ⅲ表达量均明显降低(P<0.05)。藏红花素上述作用呈一定剂量依赖性。除LVHI、IL-8外,藏红花素高剂量组对其它指标的作用明显优于卡托普利组(P<0.05)。结论藏红花素具有抑制心肌梗死后心衰大鼠心肌纤维化、改善心功能的作用,可能与抑制TLR4/NF-κB信号通路,抑制炎症反应和细胞外基质生成有关。

早期应用沙库巴曲缬沙坦对自发性高血压大鼠急性心肌梗死再灌注心功能及心室重构的影响及机制研究

目的:研究早期应用沙库巴曲缬沙坦(Sacubattril/Valsartan,SAC/VAL)对自发性高血压大鼠急性心肌梗死(acute myocardial infarction,AMI)再灌注心脏重构及心功能的影响。方法:选取60只自发高血压大鼠。随机分为对照组(n=10)和实验组(n=50)。采取结扎冠状动脉的方法建立AMI大鼠再灌注模型;实验组大鼠随机分为三组,分别术后给予安慰剂(Model);预防性给予SAC/VAL与VAL;治疗性给予SAC/VAL与VAL。术后连续观察10周,以ELisa酶联免疫吸附法检测hs-TnT、NT-proBNP、TNF-α、IL-2、IL-6和IL-10等表达水平,以超声心动图测定大鼠LVEDD、LVESD、左心室舒张末容积(left Ventricular end-diastolic volume,LVEDV)、左心室收缩末容积(left ventricular end systolic volume,LVESV)、左心室短轴缩短率(fraction shortening,FS)及LVEF;10周后处死大鼠并以苏木素伊红(HE)染色,Masson染色,并计算胶原容积分数(collagen volume fraction CVF);用Western blot分析法测定心肌组织中p-NF-κB、p-IκB的蛋白水平。结果:(1)与Sham组比较,实验各组大鼠心肌细胞肥大、排列紊乱、纤维化明显,CVF显著升高(P <0.01);hs-TnT、NT-proBNP、TNF-α、IL-2、IL-6表达水平明显升高(P <0.01),IL-10表达水平明显下降(P <0.01);超声心动图测定心脏扩大且收缩功能显著受损(P <0.01)。(2)与Model组比较,用药各组梗死交界区心肌细胞结构相对完整,肌间隙变窄,CVF显著下降(P <0.01);hs-TnT、NTproBNP、TNF-α、IL-2、IL-6水平明显降低(P <0.01),IL-10表达水平明显升高(P <0.01);LVEDD、LVESD、LVEDV、LVESV明显下降(P <0.05),FS、EF值明显增加(P <0.01)。(3)在两组治疗方案中,SAC/VAL和VAL均可改善AMI后大鼠心功能,但SAC/VAL提供了更好的心功能保护,差异具有统计学意义(P <0.01)。(4) P-SAC/VAL组与T-SAC/VAL组比较,CVF减小更加明显,hs-TnT、NT-proBNP、TNF-α、IL-2、IL-6水平明显降低(P <0.01),IL-10表达水平明显升高(P<0.01),LVEDD、LVESD、LVEDV、LVESV明显下降(P <0.01),FS、EF值明显增加(P <0.01)。(5)与Model组比较相比,治疗组心肌组织中磷酸化核因子κB(phosphorylated nuclear factorkappa B,p-NF-κB)、磷酸化κB抑制蛋白(phosphorylated inhibitor of kappa B,p-IκB)表达下调(P <0.05)。结论:(1) SAC/VAL或VAL在AMI再灌注后均可有效改善心室重构、心功能;(2)与VAL相比,SAC/VAL在预防及治疗AMI诱导的心功能障碍方面效果更佳;(3) SAC/VAL早期预防性应用可更好地改善心功能。(4) SAC/VAL可能通过下调p-NF-κB、p-IκB蛋白表达发挥保护心功能的作用。此获益可能与SAC/VAL抑制心肌炎症反应,抑制细胞凋亡,减轻心肌纤维化,改善左心室重构相关。

冠心宁片联合重组人脑利钠肽治疗急性ST段抬高型心肌梗死患者的效果

目的 评估冠心宁片与重组人脑利钠肽联合应用于急性ST段抬高型心肌梗死患者的临床治疗效果。方法 选取浙江省中西医结合医院2021年10月至2023年10月收治的80例急性ST段抬高型心肌梗死患者。采用随机数字表法将所有急性ST段抬高型心肌梗死患者分为对照组和观察组(n=40),其中对照组心肌梗死患者予以重组人脑利钠肽治疗,观察组心肌梗死患者联合使用冠心宁片和重组人脑利钠肽进行治疗。比较两组患者的总有效率、心肌损伤标志物、心功能、血管内皮功能、主要不良心血管事件(MACE)发生率。结果 观察组的总有效率为95.00%(38/40),高于对照组的77.50%(31/40)(χ^(2)=5.165,P=0.023)。治疗1个月后,观察组和对照组患者血清心肌肌钙蛋白Ⅰ(cTnⅠ)、肌酸激酶心肌同工酶(CK-MB)水平[分别是(0.24±0.03)μg·L^(-1)、(22.39±3.12) U·L^(-1)、(0.51±0.12)μg·L^(-1)、(30.07±3.86) U·L^(-1)],低于治疗前[分别是(1.42±0.26)μg·L^(-1)、(36.27±4.44) U·L^(-1)、(1.45±0.27)μg·L^(-1)、(36.02±4.41) U·L^(-1)],且观察组患者血清cTnI、CK-MB水平低于对照组(均P<0.05)。治疗1个月后,观察组和对照组患者左心室收缩末期内径(LVESD)和左心室舒张末期内径(LVEDD)分别为[(37.05±4.32) mm、(43.33±5.27) mm、(42.15±4.82) mm、(47.02±5.46) mm],均低于治疗前[分别为(48.31±5.59) mm、(48.25±5.57) mm、(53.17±6.21) mm、(53.49±6.24) mm],且观察组LVEDD、LVESD低于对照组(均P<0.05)。治疗1个月后,观察组和对照组患者左心室射血分数(LVEF)[分别为(55.67±6.45)%、(45.37±5.78)%],高于治疗前[分别为(39.12±5.03)%、(39.37±5.06)%],且观察组LVEF高于对照组(均P<0.05)。治疗1个月后,观察组和对照组患者血清内皮素-1(ET-1)、血管内皮生长因子(VEGF)水平[分别为(74.13±8.24) ng·L^(-1)、(245.38±18.69) pg·L^(-1)、(82.08±9.16) ng·L^(-1)、(316.25±27.14) pg·L^(-1)],低于治疗前[分别为(93.47±10.36) ng·L^(-1)、(448.91±32.62) pg·L^(-1)、(93.15±10.21) ng·L^(-1)、(449.26±32.65) pg·L^(-1]),且观察组血清ET-1、VEGF水平低于对照组(均P<0.05)。治疗1个月后,观察组和对照组患者血清一氧化氮(NO)水平[分别为(61.07±7.24)μmol·L^(-1)、(54.62±6.1)μmol·L^(-1)],高于治疗前[分别为(41.36±5.33)μmol·L^(-1)、(41.02±5.27)μmol·L^(-1)],且观察组血清NO水平高于对照组(均P<0.05)。观察组的MACE发生率为(7.50%)低于对照组(25.00%)(χ^(2)=4.501,P=0.034)。结论 冠心宁片联合重组人脑利钠肽治疗急性ST段抬高型心肌梗死的临床效果表现优异,能够有效减轻心肌所受损伤,同时改善心脏功能以及血管内皮的功能状态,降低MACE发生率,有一定的临床应用前景。

基于Fas/FasL信号通路探索舒芬太尼对急性心肌梗死大鼠心功能和心肌细胞凋亡的影响

目的基于脂肪酸合成酶(Fas)/脂肪酸合成酶配体(FasL)信号通路探索舒芬太尼对急性心肌梗死(AMI)大鼠心功能和心肌细胞凋亡的影响。方法选择健康雄性SD大鼠108只,适应性饲养7天,随机分为对照组、模型组、舒芬太尼低剂量组、舒芬太尼高剂量组、舒芬太尼高剂量+Fas阴性对照组、舒芬太尼高剂量+Fas慢病毒组,每组18只。模型组、舒芬太尼低剂量组、舒芬太尼高剂量组、舒芬太尼高剂量+Fas阴性对照组、舒芬太尼高剂量+Fas慢病毒组通过冠状动脉左前降支结扎法制作AMI模型;对照组除不结扎冠状动脉左前降支外,其余步骤与AMI模型相同。舒芬太尼低剂量组和舒芬太尼高剂量组分别于AMI模型制作成功后腹腔注射0.1、1µg/kg舒芬太尼。舒芬太尼高剂量+Fas阴性对照组和舒芬太尼高剂量+Fas慢病毒组分别于AMI模型制作成功后腹腔注射1µg/kg舒芬太尼,尾静脉注射200 nmol/kg NC shRNA慢病毒或Fas shRNA慢病毒。对照组和模型组腹腔注射等量生理盐水。术后72 h,采集大鼠尾静脉血,采用ELISA法检测血清肌钙蛋白T;采用超声心动图检测左心室射血分数(LVEF)、左心室缩短分数(LVFS)、左心室舒张末期内径(LVEDd)和左心室收缩末期内径(LVESd)。待大鼠心功能检测完成后,腹主动脉取血,采用ELISA法检测血清TNF-α、IL-6。所有大鼠断头处死,留取心脏,随机取6只大鼠的心脏组织,TTC染色,计算心肌梗死面积;随机取6只大鼠的心脏组织,HE染色,观察心肌组织病理形态变化,采用TUNEL法检测细胞凋亡情况;取剩余6只大鼠的心脏组织,采用Western blotting法检测细胞凋亡相关蛋白Bcl-2、Bax、Caspase-3及Fas/FasL信号通路相关蛋白表达。结果与对照组比较,模型组血清肌钙蛋白T水平升高,LVEDd、LVESd升高,LVEF、LVFS降低,血清TNF-α、IL-6水平升高,心肌梗死面积增大,细胞凋亡率及Bax、Caspase-3、Fas、FasL蛋白表达升高,Bcl-2蛋白表达下降(P均<0.05);与对照组比较,模型组心肌细胞形态模糊、纹理消失、排列紊乱、心肌间小血管扩张、细胞数量减少,可见大量炎性细胞浸润。与模型组比较,舒芬太尼低剂量组和舒芬太尼高剂量组血清肌钙蛋白T水平降低,LVEDd、LVESd降低,LVEF、LVFS升高,血清TNF-α、IL-6水平降低,心肌梗死面积减小,细胞凋亡率及Bax、Caspase-3、Fas、FasL蛋白表达降低,Bcl-2蛋白表达升高(P均<0.05);与模型组比较,舒芬太尼低剂量组和舒芬太尼高剂量组心肌细胞形态、纹理、排列、血管扩张、细胞数量及炎性细胞浸润显著改善。以舒芬太尼高剂量组上述效果改善较为明显。与舒芬太尼高剂量+Fas阴性对照组比较,舒芬太尼高剂量+Fas慢病毒组血清肌钙蛋白T水平升高,LVEDd、LVESd升高,LVEF、LVFS降低,血清TNF-α、IL-6水平升高,心肌梗死面积增大,细胞凋亡率及Bax、Caspase-3、Fas、FasL蛋白表达升高,Bcl-2蛋白表达降低(P均<0.05);与舒芬太尼高剂量+Fas阴性对照组比较,舒芬太尼高剂量+Fas慢病毒组心肌细胞形态模糊、纹理消失、排列紊乱、心肌间小血管扩张、细胞数量减少,炎性细胞浸润明显。结论舒芬太尼可改善AMI大鼠心功能,抑制心肌细胞凋亡,并且1µg/kg舒芬太尼的作用效果要优于0.1µg/kg舒芬太尼;抑制Fas/FasL信号通路激活可能是舒芬太尼改善AMI大鼠心功能的作用机制之一。

急诊PCI与延迟PCI对高血栓负荷STEMI患者预后的影响

目的探讨和分析急诊经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)及延迟PCI对高血栓负荷急性ST段抬高型心肌梗死(ST-elevated myocardial infarction,STEMI)患者预后的影响。方法非随机选取2022年1月—2023年12月在新疆兵团第一师医院住院治疗的高血栓负荷STEMI达到TIMI3级的192例患者为研究对象,根据支架置入时间分为急诊PCI组(n=64)与延迟PCI组(n=128),急诊PCI组患者实施PCI手术,延迟PCI组患者7~14 d后实施PCI手术,比较两组纽约心脏病协会分级、心功能指标、并发症情况及远期预后。结果延迟PCI组术后30、90、180 d的心功能分级均优于急诊PCI组,差异有统计学意义(P均<0.05)。与急诊PCI组相比,延迟PCI组患者STEMI发生后30、90、180 d左心室射血分数水平更高,左室舒张末期内径及脑尿钠肽水平更低,差异有统计学意义(P均<0.05)。延迟PCI组并发症总发生率为3.91%(5/128),低于急诊PCI组的14.06%(9/64),差异有统计学意义(χ^(2)=6.510,P<0.05)。延迟PCI组的心肌梗死后不稳定型心绞痛及心衰再住院情况均优于急诊PCI组,差异有统计学意义(P均<0.05)。结论与急诊PCI相比,高血栓负荷STMEI患者应用延迟PCI治疗对于改善其心功能及远期预后效果更加明显。

麝香保心丸介导的内皮功能改变对心梗后心衰患者短期预后影响的临床研究

目的分析麝香保心丸介导的内皮功能改变对心肌梗死(心梗)后心力衰竭(心衰)患者短期预后的影响。方法纳入心梗后心衰患者43例为研究对象,以随机分组方式分为对照组(21例)与观察组(22例)。两组患者均接受常规冠心病及心衰二级预防西药用药,观察组患者在常规西药治疗基础上联合麝香保心丸口服用药治疗。比较两组心功能[心率(HR)、左室射血分数(LVEF)、左室舒张末期内径(LVEDD)]、血常规指标[凝血酶原时间(PT)、血浆纤维蛋白原(FIB)、血小板聚集试验(PAgT)]、流式细胞学指标[辅助性T淋巴细胞1(Th1)、辅助性T淋巴细胞17(Th17)及调节性T细胞(Treg)]、炎性因子[白细胞介素-10(IL-10)、白细胞介素-6(IL-6)、C反应蛋白(CRP)]水平。结果观察组患者治疗1年后LVEF(59.12±3.83)%高于对照组的(55.88±3.97)%,HR(76.14±6.69)次/min、LVEDD(54.47±2.91)mm低于对照组的(80.61±5.92)次/min、(57.63±2.16)mm,统计学意义成立(P<0.05)。治疗1年后,观察组PT(13.93±2.01)s长于对照组的(12.63±2.07)s,FIB(4.02±0.98)g/L、PAgT(59.63±7.31)%均低于对照组的(4.79±1.02)g/L、(67.56±6.91)%,统计学意义成立(P<0.05)。观察组治疗1年后Th1、Th17低于对照组,Treg高于对照组,统计学意义成立(P<0.05)。治疗1年后,观察组患者IL-10(36.67±6.38)pg/ml、IL-6(130.63±24.36)pg/ml、CRP(33.12±8.93)mg/L均低于对照组的(43.08±7.11)pg/ml、(169.67±29.61)pg/ml、(49.68±10.47)mg/L,统计学意义成立(P<0.05)。结论麝香保心丸介导的内皮功能改变能显著提升心梗后心衰患者的心功能水平,增强机体免疫功能,降低机体炎症因子水平,麝香保心丸综合应用价值较高,建议临床推广使用。

氨基末端脑钠肽前体、左室射血分数及心电图碎裂QRS波群与急性心肌梗死患者不良预后的相关性研究

目的:探究氨基末端脑钠肽前体(NT-proBNP)、左室射血分数(LVEF)、心电图碎裂QRS波群(fQRS)与急性心肌梗死(AMI)患者不良预后的关系。方法:采用巢式病例对照研究方法,选取2021年1月-2023年1月于河池市第三人民医院行经皮冠状动脉介入治疗(PCI)的AMI患者96例作为研究对象,依据术后6个月是否发生主要心血管不良事件进行分组,将预后不良的患者纳入预后不良组,随后在研究队列人群中按照1∶2频数配比纳入预后良好的患者为预后良好组。收集并分析患者的临床信息,采用Logistic回归模型分析NT-proBNP、LVEF及fQRS与AMI预后不良的相关性。结果:96例AMI患者术后随访6个月发现预后不良患者19例(19.78%)。多因素Logistic回归分析结果提示,NT-proBNP水平上升、LVEF降低、发生fQRS是AMI患者不良预后的影响因素(P<0.05)。结论:NT-proBNP、LVEF、fQRS是AMI患者不良预后的影响因素,在预测心血管不良事件及预后具有重要意义。

强心利尿基础上联合诺欣妥治疗心肌梗死后心力衰竭的效果和安全性

目的探析强心利尿基础上联合诺欣妥治疗心肌梗死(MI)后心力衰竭(HF)的临床效果。方法纳入济南高新东区医院2022年6—12月经临床确诊的68例MI后HF患者,采用简单随机化方法将纳入患者分为两组,对照组34例给予强心利尿治疗,观察组34例在对照组基础上加施诺欣妥治疗,比较两组临床疗效、心功能指标、心肌损伤指标以及神经内分泌因子和不良反应发生率。结果观察组临床总有效率为94.12%,高于对照组的76.47%,差异有统计学意义(P<0.05)。治疗后,观察组左室射血分数(LVEF)、心搏出量(CO)高于对照组,左室收缩末期内径(LVDs)、左室舒张末期内径(LVDd)低于对照组,差异有统计学意义(P<0.05)。治疗后,观察组心肌肌钙蛋白I(cTn-I)、肌红蛋白(Myo)、肌酸激酶同工酶(CK-MB)均低于对照组,差异有统计学意义(P<0.05)。治疗后,观察组N末端脑钠肽前体(NT-pro BNP)、血清肾素(RA)、血管紧张素Ⅱ(AngⅡ)均低于对照组,差异有统计学意义(P<0.05)。观察组低血压、胃肠道反应、心律失常以及血管性水肿不良反应总发生率为5.88%,与对照组的8.82%比较,差异无统计学意义(P>0.05)。结论在强心利尿基础上采用诺欣妥治疗MI后HF,整体效果较好,改善心功能指标、心肌损伤指标以及神经内分泌因子水平作用显著,不良反应较少,值得临床推广、应用。