Interleukin-4 and cardiac fibrosis in patients with heart failure

Interleukin-4 (IL-4) stimulates inflammatory responses, activates collagen synthesis, promotes fibrosis progression, and inhibits the production of inflammatory cytokines. We studied the relationship between the urinary IL-4 level and levels of markers of cardiac fibrosis and left ventricular volume in 98 patients with heart failure (HF). The left ventricular end-systolic volume index (LVESVI) and left ventricular end-diastolic volume index (LVEDVI) were calculated, and IL-4, tumor necrosis factor-alpha (TNF-alpha), IL-6, and aminoterminal propeptide of procollagen type III (PIIINP) levels were recorded. Comparison of urinary IL-4 and PIIINP levels in patients and control subjects gave values of 12 (12) pg/mL and 4 (3) pg/mL (P<.0001), respectively, and 5 (2) ng/mL and 4 (1) ng/mL (P<.0001), respectively. The IL-4 level correlated with LVESVI and LVEDVI (r = -0.22, P<.05), and with PIIINP (r = 0.24, P<.05). In patients with hypertensive cardiomyopathy, there was a good correlation between IL-4 and PIIINP levels (r = 0.7, P<.01). Correlations were also observed between IL-4 and TNF-alpha (r = 0.3, P<.01) and IL-6 (r = 0.5, P<.0001). The urinary IL-4 level correlated with cardiac fibrosis and remodeling in patients with HF. The relationship was stronger in those with hypertensive cardiomyopathy.     

Myocardial remodeling and immunologic activation in patients with heart failure

INTRODUCTION AND OBJECTIVES: Immune response-mediated regulation of myocardial collagen remains poorly understood. Our objective was to investigate the relationship between ventricular remodeling and immunologic activation in patients with heart failure (HF) by comparing dilated and ischemic cardiomyopathy. METHODS: We studied 94 patients with HF and dilated cardiomyopathy (n=46) or ischemic cardiomyopathy (n=48). We recorded left ventricular (LV) volumes, E/A ratio, and ejection fraction. Plasma concentrations of tumor necrosis factor alpha (TNFalpha), soluble TNFa receptor I (sTNF-RI), sTNF-RII, interleukin-6 (IL-6) and IL-10 were measured. The serum procollagen type-III amino-terminal propeptide (PIIINP) level was also obtained. RESULTS: Ventricular volumes were greater in the dilated cardiomyopathy than in the ischemic cardiomyopathy group (P< .05). However, sTNF-RI, sTNF-RII and PIIINP levels were higher in the ischemic group (P< .05). In this group, there were significant correlations between ventricular volumes and IL-10 and sTNF-RII levels. There was also a significant correlation between PIIINP and sTNF-RII levels (r=0.30; P< .05). In the dilated cardiomyopathy group, there was a significant correlation between ventricular volumes and IL-10 level, and between PIIINP level and IL-6 (r=0.32; P< .05) and sTNF-RII levels (r=0.32; P< .05). Multiple linear regression analysis, which included cytokine levels, age, sex and ventricular function, showed that the sTNF-RII level was an independent predictor of the PIIINP level (adjusted r(2)=0.16; P< .0001) and of ventricular volumes (LV end-systolic volume index, adjusted r(2)=0.034; P< .05; and LV end-diastolic volume index, adjusted r(2)=.048; P< .05) in both groups. CONCLUSIONS: In HF, there is an interaction between proinflammatory cytokines and the extracellular matrix. Immunologic implications vary according to disease etiology. The elevation in proinflammatory cytokine and PIIINP levels is greater in patients with ischemic cardiomyopathy. Multiple regression analysis showed that the sTNF-RII level was an independent predictor of ventricular remodeling.     

Diverse effect of inflammatory markers on insulin resistance and insulin-resistance syndrome in the elderly

OBJECTIVES: To evaluate the potential association between different inflammatory markers and insulin resistance (IR), as well as insulin-resistance syndrome (IRS) in a large, population-based study of older, nondiabetic persons. DESIGN: Cross-sectional study. SETTING: Outpatient clinic in Greve in Chianti and Bagno a Ripoli (Italy). PARTICIPANTS: One thousand one hundred forty-six nondiabetic subjects ranging in age from 22 to 104. MEASUREMENTS: Anthropometric measurements; plasma fasting levels of glucose, insulin, and cholesterol (total, high-density lipoprotein, low-density lipoprotein); homeostasis model assessment to estimate degree of insulin resistance; tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), soluble IL-6 receptor (sIL-6R), interleukin receptor antagonist (IL-1ra), and C-reactive protein (CRP) plasma concentrations; diastolic, systolic, and mean arterial blood pressure; and echo-color-Doppler duplex scanning examination of carotid arteries. RESULTS: Insulin resistance correlated with age (r=0.102; P<.001) and plasma levels of TNF-alpha (r=0.082; P=.007), IL-1ra (r=0.147; P<.001), IL-6 (r=0.133; P<.001), sIL-6R (r=-0.156; P<.001), and CRP (r=0.83; P<.001). Subjects in the upper tertile of IR degree were older and had higher serum levels of TNF-alpha, IL-1ra, and IL-6 and lower levels of sIL-6R than subjects in the lowest tertile. Independent of age, sex, body mass index, waist-to-hip ratio, triglycerides, drug intake, diastolic blood pressure, smoking habit, and carotid atherosclerotic plaques, higher IL-6 (t=2.987; P=.003) serum concentrations were associated with higher IR, whereas sIL-6R levels (t=-5.651; P<.001) were associated with lower IR. Furthermore, IL-1ra concentrations (t=2.448; P=.015) were associated with IRS, and higher sIL-6R plasma levels continued to correlate negatively with IRS. CONCLUSION: Different inflammatory markers are associated with a diverse effect on IR and IRS in elderly nondiabetic subjects.     

Tumour necrosis factor-alpha and interleukin-6 release during primary percutaneous coronary intervention for acute myocardial infarction is related to coronary collateral flow

OBJECTIVES: We tested the hypothesis that there was an association between tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) release and measured coronary collateral flow in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: Tumour necrosis factor-alpha and IL-6 increase during acute myocardial infarction (AMI). However, their relation to coronary collateral flow is unknown. METHODS: Twelve patients with AMI due to complete thrombotic coronary occlusion underwent primary PCI within 12 h of symptom onset. Doppler-derived collateral flow index (CFI) was measured during first balloon inflation. TNF-alpha, IL-6, creatine kinase (CK), CK-MB fraction were measured from venous plasma samples serially for 24 h. Area at risk was determined off-line by coronary arteriography. Ejection fraction (EF) was measured using biplane left ventricular angiography. RESULTS: Maximal CK release varied between 569 and 6276 U/l and area at risk varied between 7 and 47% of myocardium. Tumour necrosis factor-alpha (peak 4.4+/-0.5 pg/ml) and IL-6 (peak 35.5+/-3.0 pg/ml) increased in all patients. Peak TNF-alpha and IL-6 release was independent of CK, CKMB. No minimal threshold of myocardial necrosis for cytokine expression could be detected. Similarly, TNF-alpha and IL-6 release was also independent of time to reperfusion, area at risk or EF. Using univariate regression analysis, peak TNF-alpha inversely correlated with CFI (r = 0.67, P = 0.017) whereas IL-6 positively correlated with CFI (r = 0.76, P = 0.004). CONCLUSIONS: Acute myocardial infarction is associated with a significant rise in TNF-alpha and IL-6 levels independent of infarct size or myonecrosis. Tumour necrosis factor-alpha and IL-6 correlate dichotomously with CFI indicating differing roles in reperfused AMI.     

缬沙坦合用安体舒通对急性心肌梗死伴室壁瘤患者血运重建后的血清胶原水平和心功能的影响

目的:研究缬沙坦及合用安体舒通对经再灌注治疗的急性心肌梗死患者血清胶原水平和心功能的影响。方法:首次急性前壁心肌梗死伴室壁瘤患者70例,随机分为缬沙坦组、合用药组(缬沙坦合用安体舒通),在治疗后1周、2周、12周测定血清Ⅰ型前胶原羧基末端肽(PⅠCP)和Ⅲ型前胶原氨基末端肽(PⅢNP)浓度;并在治疗后2周、12周进行二维超声心动图检查。结果:12周时合用药组血清PⅢNP、血清PⅠCP较缬沙坦组明显降低(P0.05)。合用药组的舒张末期容积指数、收缩末期容积指数、局部室壁运动指数、左室射血分数及左室质量指数较缬沙坦组明显改善(P0.05)。结论:缬沙坦能够阻抑急性心肌梗死伴室壁瘤患者的胶原合成,改善心室收缩和舒张功能;合用药组的作用优于单用缬沙坦,显著改善心室收缩和舒张功能。     

Baseline glucose and left ventricular remodeling after acute myocardial infarction

In patients with acute myocardial infarction (AMI), the mechanisms behind the increased mortality related to glucose levels (GL) are poorly understood. The main purpose of this study is to analyze the relationship between baseline glucose and left ventricular enlargement (LVE). We analyzed 52 patients with a first ST-elevation AMI <24 h of evolution. Glucose levels were obtained upon admission (median time, 3 h after the beginning of chest pain). The median GL was 123.5 mg/dl, and patients above this limit were considered hyperglycemic (n=26). Left ventricular enlargement was analyzed comparing two radionuclide ventriculographies, the first obtained within 4 days post-AMI (median, 55 h) and the second 6 months later (median, 188.5 days), taking into account the difference in the obtained end-systolic volumes. Myocardial reperfusion was evaluated comparing ST resolution between a first ECG done immediately upon hospital arrival with a second ECG performed 2 h after treatment. By univariate analysis, LVE correlated significantly with baseline hyperglycemia (P<.001), failed reperfusion by ECG criteria (P<.001), and no use of ACE inhibitors or AT1 blockers (P=.046) and aspirin (P=.046). A history of previous diabetes did not correlate significantly with LVE at 6 months. In the adjusted model, basal hyperglycemia (P<.001) and failed reperfusion (P=.001) were the only variables independently correlated with LVE. In conclusion, baseline glucose is a powerful and independent predictor of LVE after AMI, which reinforces the importance of a tight glucose control during the initial phase of the disease.     

急性心肌梗死介入治疗后临床预后与白细胞介素-6的关系

目的观察急性心肌梗死(AMI)介入治疗后,白细胞介素6(IL-6)水平、白细胞计数和单核细胞比及高敏C反应蛋白(hs-CRP)与心脏收缩功能及心脏事件的关系。方法32例首次前壁AMI行急诊介入治疗患者,记录患者AMI介入治疗后24 h白细胞计数、单核细胞比及hs-CRP水平,AMI后第3天测定患者血浆IL-6水平,随访6个月。25例无冠心病病史,且超声心动图检查正常者为对照组。结果AMI组IL-6水平高于对照组(P<0.05);IL-6水平与心功能Killip分级呈正相关(r=0.64,P<0.01);与AMI后3个月及6个月时左室射血分数呈负相关,r值分别为-0.59及-0.47(均P<0.01);Killip分级≥2级、严重心律失常、心包积液患者的IL-6水平明显高于无心脏事件的患者,P<0.05;Killip分级≥2级的患者hs-CRP水平明显高于Killip分级1级的患者。结论IL-6是AMI左室收缩功能严重受损以及发生心脏事件的预测因子。     

Inflammatory markers and physical performance in older persons: the InCHIANTI study

BACKGROUND: Some studies have proposed chronic inflammation as an underlying biological mechanism responsible for physical function decline in elderly people. The aim of this study is to evaluate the relationship between several inflammatory markers and physical performance in an older population. METHODS: This study is part of the "Invecchiare in Chianti" (InCHIANTI) study, a prospective population-based study of older people, aimed at identifying risk factors for late-life disability. The study sample consisted of 1020 participants aged 65 years and older living in the Chianti area of Italy. Physical performance was assessed using walking speed, the chair-stand test, and the standing balance test. Hand-grip strength was assessed using a hand-held dynamometer. Serum levels of C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), IL-10, IL-1beta, IL-6sR, and IL-1RA were determined. Linear regression analyses were used to assess the multivariate relationship of inflammatory marker levels with physical performance, scored as a continuous variable from 0 to 3, and hand-grip strength after adjustment for demographics, chronic conditions, medication use, and other biological variables. RESULTS: CRP, IL-6, and IL1RA were significantly correlated with physical performance (r=-0.162, r=-0.251, and r=-0.127, respectively). Significant correlations with hand-grip strength were found for CRP and IL-6 (r=-0.081 and r=-0.089, respectively). After adjustment for covariates, high levels of IL-6 and IL-1RA continued to be strongly associated with worse physical performance (p<.001 and p=0.004, respectively). High levels of CRP (p<.001) and IL-6 (p<.001) were associated with low hand-grip strength. Mean adjusted physical performance scores ranged from 2.21 in the CRP<0.59 mg/dl group to 2.07 in the CRP>0.60 mg/dl group (p for trend=.004), and from 2.25 in the lowest IL-6 quartile to 2.08 in the highest IL-6 quartile (p for trend<.001). This trend was also reflected in mean adjusted hand-grip strength, with a range from 28.8 kg for the CRP<0.59 mg/dl group to 26.0 kg for the CRP>0.60 mg/dl group (p for trend=.001), and from 27.4 kg for the lowest IL-6 quartile to 25.1 kg for the highest IL-6 quartile (p for trend=.001). CONCLUSIONS: Inflammation, measured as high levels of IL-6, CRP, and IL-1RA, is significantly associated with poor physical performance and muscle strength in older persons. These data also support the biological face validity of physical performance measures. The assessment of inflammatory markers may represent a useful screening test and perhaps a potential target of intervention.     

白细胞介素-6及C-反应蛋白与急性心肌梗死后心室重构的相关性研究

目的:评价血清白细胞介素6(IL6)和C反应蛋白(CRP)对心肌梗死后心室重构的预测价值。方法:测定64例首次急性心肌梗死患者发病72小时的IL6和CRP及第14天的超声心动图,根据IL6浓度将患者分成高IL6组和低IL6组,比较两组间心室重构各指标。结果:高IL6组CRP浓度、左心室舒张末容积(LVEDV)、左心室收缩末容积(LVESV)、左心室重构(LVRM)总的发生率明显升高,左心室射血分数(LVEF)降低,与低IL6组比较均有统计学差异(P<0.05)。两组室壁瘤发生率无统计学差异(P>0.05)。血清IL6与血清CRP、左心室舒张末容积、左心室收缩末容积、室壁瘤、心室重构均呈显著正相关,与左心室射血分数呈显著负相关。血清CRP与左心室收缩末容积、室壁瘤、心室重构呈显著正相关,与左心室射血分数呈显著负相关,但是与左心室舒张末容积无显著相关性。CRP进入Logistic回归方程。结论:心肌梗死后72小时高水平IL6和CRP与心肌梗死后心室重构呈正相关,血清高CRP浓度是预测心肌梗死急性期发生心室重构的独立预测因素。     

Relation of QT dispersion to infarct size and left ventricular wall motion in anterior wall acute myocardial infarction.

Previous studies have shown that QT dispersion increases during acute myocardial infarction (AMI). However, the relation of QT dispersion to infarct size and left ventricular (LV) function in AMI has not yet been fully clarified. Accordingly, this study was conducted to elucidate this relation at 1 month after anterior wall AMI. We examined 94 patients with first anterior wall AMI (< or = 6 hours) who underwent coronary arteriography at admission, 1 month, and 6 months after AMI, and left ventriculography at 1 and 6 months after AMI. Mean QT dispersion on the chronic phase (about 1 month after AMI) electrocardiogram was 79 +/- 33 ms. There were no significant correlations between QT dispersion and peak creatine phosphokinase levels, LV ejection fraction, and regional wall motion in the infarct region at 1 month after AMI (r = 0.06, p = 0.57; r = 0.11, p = 0.29; r = -0.05, p = 0.63, respectively). In conclusion, the findings of this study suggest that QT dispersion on the resting electrocardiogram at 1 month after anterior wall AMI is unrelated to infarct size estimated by the peak creatine phosphokinase level and the degree of LV dysfunction.     

Serum uric acid levels correlate with filling pressures in systolic heart failure

The authors studied the relationship between liver function tests and serum uric acid level with clinical and hemodynamic profiles in heart failure. Fifty patients (aged 44±15 years; 74.5% men) with an ejection fraction (EF) <35% were enrolled and clinical assessment was performed. Hemodynamic indices (including pulmonary arterial pressure [PAP], pulmonary capillary wedge pressure [PCWP], and cardiac index were studied by standard Edwards Lifesciences Swan-Ganz catheters, and liver function tests and serum uric acid level were measured simultaneously. Fifty age- and sex-matched controls with normal EF were also studied. A total of 73% of patients had ischemic cardiomyopathy. Mean uric acid level was 7.2±3.8 mg/dL and was significantly higher than in the control group (P value<.001). In multivariate analysis, uric acid correlated significantly with PAP (r=.5, P<.001) and PCWP (r=.4, P=.002) and was also associated with clinical signs of rales, edema, paroxysmal nocturnal dyspnea (r=.5, P=.01), and New York Heart Association class (r=.4, P=.005). Uric acid level was also correlated inversely with left ventricular EF (r=.27, P=.006). Elevated uric acid levels in patients with systolic heart failure is associated with impaired clinical and hemodynamic profile and might be used as a noninvasive indicator of elevated left ventricular filling pressures.     

Soluble tumor necrosis factor receptor 2 is independently associated with pulse wave velocity in nonobese Japanese patients with type 2 diabetes mellitus

The aim of the present study was to investigate the factors contributing to pulse wave velocity (PWV) in patients with type 2 diabetes mellitus. We focused on tumor necrosis factor (TNF) including soluble TNF receptors (sTNF-R1, sTNF-R2) in this study because TNF seems to be associated with the progression of atherosclerosis and because the relationships between PWV and TNF were not yet examined in type 2 diabetic patients. Univariate regression analyses showed that PWV was positively correlated with age (r=0.492, P<.001), diabetes duration (r=0.251, P=.021), systolic (r=.595, P<.001) and diastolic (r=0.248, P=.022) blood pressure, antihypertensive medication (r=0.268, P=.013), and the concentrations of sTNF-R1 (r=0.354, P=.001) and sTNF-R2 (r=0.415, P<.001). Although there was a positive correlation between TNF-alpha and sTNF-R1 (r=0.382, P<.001) or sTNF-R2 (r=0.394, P<.001), TNF-alpha was not associated with PWV. Other variables including gender were not associated with PWV. Multiple regression analyses showed that PWV was independently predicted by the level of age (F=15.1), systolic blood pressure (F=31.6), and sTNF-R2 (F=5.2), which explained 49.2% of the variability of PWV. From these results, it can be concluded that serum soluble TNF receptor is an important independent factor associated with aortic PWV in type 2 diabetic patients.     

Plasma tissue inhibitor of metalloproteinase-1 levels are elevated in essential hypertension and related to left ventricular hypertrophy

BACKGROUND: Essential hypertensive patients have an increased heart and arterial collagen concentration. Increased collagen synthesis can be assessed using procollagen III N peptide (PIIINP) and reduced collagen degradation measured using tissue inhibitor of metalloproteinase-1 (TIMP-1). METHODS: Plasma TIMP-1 and PIIINP levels were measured in 31 patients with essential hypertension and in 17 normotensive control subjects. The hypertensive patients were either treatment naive (n = 18) or had been without treatment for 1 month (n = 13). Both groups of patients were screened to exclude other fibrotic diseases. RESULTS: In the hypertensive patients, TIMP-1 levels were significantly (P < .0002) elevated (median 380 ng/ mL, range 160 to 1,560 ng/mL) compared with those of the normotensive control subjects (median 178 ng/mL, range 99 to 330 ng/mL). In hypertensive subjects who had never received antihypertensive therapy there were significant correlations between TIMP-1 and left ventricular posterior wall thickness in diastole (LVPWd) (r = 0.58) (P < .02) and left ventricular mass index (r = 0.58) (P < .02). There was no difference in PIIINP levels (mean +/- 2 SD) between the hypertensive (0.56 U/mL +/- 0.3) and normotensive groups (0.52 U/mL +/- 0.2). CONCLUSIONS: The increased tissue collagen III levels found in the heart and vessels of hypertensive patients is due to a reduction in collagen degradation because of high TIMP-1 levels, rather than an increase in synthesis of collagen type III. The tissue source of this TIMP-1 is unclear.     

The reciprocal association of adipocytokines with insulin resistance and C-reactive protein in clinically healthy men

In experimental models, adiponectin improves and tumor necrosis factor alpha (TNF- alpha ) impairs insulin action, and the expression of these adipocytokines seems to have a reciprocal regulation. The aim was to examine whether in a cross-sectional study, associations supporting this concept may be found in 58-year-old clinically healthy men, and also the relation to C-reactive protein (CRP). In 102 men, euglycemic hyperinsulinemic clamp was used to assess glucose infusion rate (GIR). Total body fat (dual-energy x-ray absorptiometry), plasma adiponectin (radioimmunoassay), TNF-alpha , and CRP (enzyme-linked immunosorbent assay) were measured. Adiponectin correlated positively to GIR (r=0.33, P<.001) and negatively to total fat mass (r=-0.29, P=.004), whereas TNF- alpha showed reverse associations (r=-0.31, P<.01, and r=0.31, P<.01). Adiponectin and TNF- alpha were negatively correlated (-0.28, P=.006). An interaction term (TNF- alpha /adiponectin ratio) and body fat together explained 31.3% (P<.001) in GIR variability. The odds ratio for having insulin resistance was 9.3 (95% CI, 2.2-38.9) in subjects with TNF-alpha values above and adiponectin levels below the median, as compared to subjects with TNF- alpha values below and adiponectin levels above the median. Total fat and TNF-alpha , but not adiponectin, were significantly associated with log CRP (R2=20%, P<.001). In conclusion, this study in man showed that plasma adiponectin and TNF-alpha were independently and reversely associated with insulin resistance. C-reactive protein levels were related to TNF-alpha and obesity.     

Influence of primary coronary intervention on myocardial collagen metabolism and left ventricle remodeling predicted by collagen metabolism markers

The aims of the present study were to analyze cardiac collagen metabolism changes in vivo during acute and nonacute phases of ST elevation myocardial infarction (STEMI) in patients who were treated with primary coronary intervention (PCI) only, and to determine the predictive significance of collagen I and III synthesis markers (PICP, PIIINP) as well as the collagen I degradation marker (ICTP) on left ventricular function and volume changes after STEMI. Serum levels of the carboxy-terminal propeptide of type I procollagen (PICP) and amino-terminal propeptide of type III procollagen (PIIINP) assessed on the 30th day and the carboxyterminal telopeptide located at the C end of collagen type I (ICTP) assessed on the 7th day after STEMI were significantly higher (P = 0.01, P = 0.019, P = 0.04, respectively) in the PCI unsuccessful group than in the PCI successful group. These findings support the theory that early and successful PCI not only limits the amount of muscle necrosis but also protects cardiac collagen from ischemia-related injury. PICP and PIIINP levels assessed on the fourth day after acute STEMI enables us to predict the development of left ventricular function (EF) and end-diastolic volume changes over the course of 6 months, irrespective of the initial EF or revascularization success.     

Effects of Mycobacterium avium complex-infection treatment on cytokine expression in human immunodeficiency virus-infected persons: results of AIDS clinical trials group protocol 853

Human immunodeficiency virus (HIV) type 1-infected persons with newly diagnosed Mycobacterium avium complex (MAC) bacteremia were enrolled in an 8-week study to determine whether treatment of MAC infection is associated with decreases in plasma tumor necrosis factor (TNF)-alpha levels. Blood specimens were obtained for quantitative MAC cultures and to determine plasma levels of HIV RNA, TNF-alpha, and other proinflammatory cytokines. MAC levels decreased by 1.75 log at week 4 (P=.008) and by 2.48 log at week 8 (P=.001). Plasma TNF-alpha decreased by 0.15 log at week 4 (P=.042) and by 0. 40 log at week 8 (P=.027). Plasma interleukin (IL)-6 decreased by 0. 56 log at week 8 (P=.039). There were nonsignificant trends (P<.10) for plasma levels of IL-1beta and HIV RNA to decrease at week 8. Nonsignificant decreases in plasma levels of TNF-alpha, IL-1beta, IL-6, and HIV RNA were also seen in those individuals who remained on stable antiretroviral therapy throughout the 8 weeks of the study.     

尿激酶原对急性心肌梗死模型大鼠心功能的保护作用及机制探究

目的 探究尿激酶原对急性心肌梗死(AMI)模型大鼠心功能的保护作用及可能机制.方法 36只SD大鼠,采用随机数字法分为Sham组(n=12)、AMI组(n=12)和尿激酶原组(n=12).采用结扎左冠状动脉前降支的方法建立大鼠AMI模型.建模后,尿激酶原组大鼠每天经尾静脉注射2.5 mg/kg尿激酶原,Sham组和AM...     

早期美托洛尔治疗对急性心肌梗死大鼠心肌炎症因子表达和心功能的影响

目的探讨早期β受体阻断剂—美托洛尔治疗对大鼠急性心肌梗死(AMI)后心肌炎症因子和心功能的影响。方法结扎大鼠左前降支,建立AMI模型,存活随机分为梗死对照组(MI组)和美托洛尔治疗组(MI-B组),另设假手术组(S组)。MI-B组参照中国心脏病研究(CCS-2)方案给予4周美托洛尔治疗,MI组和S组仅以等体积生理盐水灌胃,观察4周后美托洛尔对心肌炎症和心功能的影响。结果与S组相比,MI组心肌组织中促炎性细胞因子TNF-α、IL-1β、IL-10和抗炎性细胞因子IL-10表达明显升与MI组比较,MI-B组心肌细胞内TNF-α和IL-1β表达明显下降,IL-10表达升高,而IL击和浸润心肌组织的淋巴细胞数差异无统计学意义。心脏超声显示MI-B组左室功能明显改善。结论早期美托洛尔治疗AMI可以改善心肌炎症因子表达和心脏功能。美托洛尔有效改善心功能的作用机制至少部分与其降低心肌细胞促炎细胞因子和升高抗炎因子的免疫药理学作用有关。     

Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure

OBJECTIVES: We sought to evaluate the effects of spironolactone on neurohumoral factors and left ventricular remodeling in patients with congestive heart failure (CHF). BACKGROUND: Aldosterone (ALD) promotes collagen synthesis and structural remodeling of the heart. Spironolactone, an ALD receptor antagonist, is reported to reduce mortality in patients with CHF, but its influence on left ventricular remodeling has not been clarified. METHODS: Thirty-seven patients with mild-to-moderate nonischemic CHF were randomly divided into two groups that received treatment with spironolactone (n = 20) or placebo (n = 17). We measured left ventricular volume and mass before treatment and after four months of treatment. We also measured the plasma levels of neurohumoral factors, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), as well as plasma procollagen type III aminoterminal peptide (PIIINP), a marker of myocardial fibrosis. RESULTS: Left ventricular volume and mass were significantly decreased and ejection fraction was significantly increased in the spironolactone group, while there were no changes in the placebo group. Plasma levels of ANP, BNP and PIIINP were significantly decreased after spironolactone treatment, but were unchanged in the placebo group. There was a significant positive correlation between the changes of PIIINP and changes of the left ventricular volume index (r = 0.45, p = 0.045) as well as the left ventricular mass index (r = 0.65, p = 0.0019) with spironolactone treatment. CONCLUSIONS: These findings indicate that four months of treatment with spironolactone improved the left ventricular volume and mass, as well as decreased plasma level of BNP, a biochemical marker of prognosis and/or ventricular hypertrophy, suggesting that endogenous aldosterone has an important role in the process of left ventricular remodeling in nonischemic patients with CHF.     

Acute myocardial infarction induced increases in plasma tumor necrosis factor-alpha and interleukin-10 are associated with the activation of poly(ADP-ribose) polymerase of circulating mononuclear cell

Systemic inflammatory response to acute myocardial infarction (AMI) is detrimental to heart function. In this study, we proved that poly(ADP-ribose) polymerase (PARP) activity of circulating mononuclear cell (MNC) increased significantly in post-AMI patients. MNC PARP activity was correlated positively with plasma tumor necrosis factor-alpha (TNF-alpha) level, interleukin-10 (IL-10) level and the ratio of plasma TNF-alpha/IL-10 respectively. On the contrary, MNC PARP activity was correlated negatively with left ventricular ejection fraction and left ventricular fractional shortening which were measured with echocardiography in the same day when blood sample was collected. These results implicated that activation of PARP in MNC contributes to the increases in plasma TNF-alpha and IL-10 and is associated with systolic dysfunction of heart after AMI.