Interleukin-6 and tumor necrosis factor alpha in relation to myocardial infarct size and collagen formation

BACKGROUND: Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) levels increase after acute myocardial infarction (AMI) in humans. Experimental data suggest that these cytokines regulate the initiation of scar formation after AMI. We investigated the interrelationships of IL-6 and TNF-alpha, tissue injury, infarct size, cardiac function, and collagen formation in humans. METHODS: Serum and plasma samples were taken on 93 patients receiving thrombolytic treatment for their first AMI. Collagen formation was evaluated by measuring concentrations of serum aminoterminal propeptide of type III procollagen (PIIINP). RESULTS: IL-6 levels increased by 44% (P<.001) and peaked at 24 hours. Peak IL-6 levels correlated positively with area under the curve of creatine kinase MB mass (r=.31, P<.01), peak troponin T level (r=.34, P<.005), and PIIINP measured at discharge (r=.46, P<.001). There were no changes in TNF-alpha levels, and patients with left ventricular dysfunction (EF<40%) had similar TNF-alpha levels as those with preserved left ventricular function. CONCLUSIONS: IL-6 may regulate collagen formation and thus remodeling of the left ventricle after AMI. In addition, TNF-alpha measurement is useless in the assessment of infarct size or left ventricular function during the immediate post-infarction period.     

Proinflammatory cytokines and myocardial viability in patients after acute myocardial infarction

BACKGROUND: Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) can potentiate heart muscle damage during acute myocardial infarction (AMI). Whether changes in their plasma levels after AMI are dependent on the presence of myocardial viability is unclear. The aim of the study was to estimate the relation of time course of plasma TNF-alpha and IL-6 and the presence of reversible and irreversible myocardial dysfunction in patients early after AMI treated thrombolytically. MATERIAL AND METHODS: Patients (54; mean age 60.4 +/- 11.7 years) with AMI plasma TNF-alpha and IL-6 were evaluated on the 2nd, 10th and 30th day after thrombolysis. Based on the response of dysfunctional segments of myocardium during dobutamine stress echocardiography performed on the 10th day, patients were divided into four groups: A, sustained improvement in contractility; B, biphasic (improvement followed by worsening); C, only worsening; D, no change. Twenty-two healthy persons served as controls. RESULTS: On the 2nd day, all four groups of patients demonstrated increased levels of TNF-alpha and IL-6 and did not differ among one another regarding both cytokines. On the 10th day, plasma TNF-alpha and IL-6 decreased in each group and were the lowest in group A, intermediate in group B and the highest in groups C and D. On the 30th day, both cytokines were not different among all studied groups. CONCLUSION: Elevated plasma TNF-alpha and IL-6 early after AMI decreased more quickly in patients with dysfunctional myocardium comprising not only necrotic but also viable segments. This decline is attenuated by the presence of residual ischemia.     

Activated toll-like receptor 4 in monocytes is associated with heart failure after acute myocardial infarction

Peripheral monocytosis may affect the development of heart failure (HF) after acute myocardial infarction (AMI). Activated toll-like receptor (TLR) 4 in monocytes plays an important role in the synthesis of proinflammatory cytokines. We examined TLR4 expression in monocytes, which may be a possible source of proinflammatory cytokines in AMI. Sixty-five patients with AMI and 20 healthy subjects (HS) were studied. Monocytes were isolated from peripheral blood on days 1 and 14 after the onset of AMI. TLR4 levels in monocytes were measured using real-time RT-PCR and flow cytometry. Generation capacity was evaluated by TLR4 levels and cytokine concentrations in the culture medium with lipopolysaccharide (LPS) stimulation. On day 1 after onset, baseline levels of TLR4 and plasma proinflammatory cytokines, notably IL-6 and TNF-alpha, were higher in AMI patients than in HS. These levels remained elevated in AMI patients 14 days after onset. Generation capacities of TLR4 and proinflammatory cytokines (IL-2, IL-6, IL-8, IL-10, GM-CSF and TNF-alpha) were increased in AMI patients compared to HS. LPS-stimulated TLR4 levels were positively correlated with IL-6 and TNF-alpha levels in AMI patients. Baseline TLR4 levels and plasma proinflammatory cytokine (IL-6, GM-CSF and TNF-alpha) levels were higher in AMI patients with HF (n = 22) than in those without HF. Generation capacities of TLR4 and proinflammatory cytokines (IL-6, GM-CSF and TNF-alpha) were greater in AMI patients with HF than in those without HF. Activation of TLR4 through a myocytic inflammatory reaction is associated with HF after AMI. These observations suggest that TLR4 signaling in monocytes may play a role in the development of HF after AMI.     

TNF-α和IL-6检测在急性冠脉综合征发病中的意义

目的　探讨急性冠脉综合征患者血清TNF -α和IL -6的浓度与发病的关系。方法　选择急性冠脉综合征 (急性心肌梗死及不稳定心绞痛 )患者 3 6例 ,其中急性心肌梗死 7例 ,不稳定心绞痛患者 2 9例。根据不稳定心绞痛患者病情的严重程度将其按Braunwald分级分为三组 :Ⅰ级 9例 ;Ⅱ级 8例 ;Ⅲ级 12例。采用放免法测定急性冠脉综合征患者血清TNF -α和IL -6的浓度。结果　不稳定心绞痛患者由Ⅰ级组到Ⅲ级组随病情加重IL -6的浓度是逐渐升高的(P <0 .0 5 ) ,但血清TNF -α无明显升高 ;急性心肌梗死患者血清IL -6浓度在心梗发作后 6小时和 48小时有两个高峰 ,血清TNF -α在心梗发作后 2 4小时达到高峰 ;IL -6和TNF -α与反映心肌损伤的酶CK -MB无直线相关性。结论　不稳定的心绞痛患者随着病情加重体内IL -6水平逐步升高 ;AMI患者发病过程中伴随IL -6和TNF -α的升高 ,但IL -6和TNF -α的动态曲线不同 ;IL -6和TNF -α浓度的升高与AMI的心肌损伤严重程度无关     

Plasma levels of neuropeptide Y i patients with current myocardial infarction

Neuropeptide Y (NPY) has been recently characterised as one of the strongest circulating vasoconstrictor peptides, its elevated level may cause coronary artery spasm and increase of peripheral vascular resistance. All this contributes to ischemic myocardial damage and decrease of regional and global left ventricular function. The aim of the study was the examination of NPY plasma levels in patients with acute myocardial infarction (AMI) after thrombolytic therapy with or without reperfusion. The survey was made in 82 patients with AMI after thrombolytic therapy: 40 of them without reperfusion and 42 with reperfusion. The control group consisted of 20 healthy persons. Plasma levels of NPY were measured before thrombolysis, then 1, 3 and 5 days after, using a radioimmunologic method. All patients were treated with aspirin, glyceryl trinitrate and thrombolytic therapy (TT) with alteplase (r-TPA). In patients with AMI, NPY plasma levels were normal before and 1 day after TT, and were significant elevated 3 days after TT 5 days after TT, plasma NPY levels were still high in patients without reperfusion, but they decreased in patients with reperfusion. There was significant negative correlation between NPY level and left ventricular ejection fraction measured 5 days after AMI. During 30-days follow up systolic dysfunction of left ventricle with ejection fraction under 40% occurred in 21 patients and in 11 of them clinical symptoms of heart failure were observed. Using the multivariable regression analysis we showed that NPY concentration over 60 pg/ml is the independent factor leading to left ventricle systolic dysfunction. The results of our study suggest the contribution of NPY to the left ventricular remodeling after AMI.     

左旋卡尼汀对急性心肌梗死急诊经皮冠状动脉介入治疗患者炎症反应的作用

目的 探讨急性心肌梗死(AMI)急诊经皮冠状动脉介入治疗(PCI)患者时左旋卡尼汀(L-CN)对炎症因子的影响.方法 发病12小时内ST段抬高AMI接受PCI的患者42例,随机分为L-CN治疗组(22例)和非治疗组(20例),再选择健康者作为对照组(22例);于PCI术前和术后第1、2、3,7天取静脉血,测定血清超敏C反应蛋白(hsCRP)和白细胞介素-6(IL-6)含量.结果 PCI术前AMI患者的hsCRP和IL-6水平较对照组明显增高(P＜0.01);术后hsCRP和IL-6水平进一步升高,明显高于术前(P均＜0.01);L-CN治疗组PCI术后hsCRP、IL-6的各时间段总和以及峰值浓度明显低于非治疗组(P＜0.01或＜0.05);IL-6与hsCRP水平呈显著正相关(P＜0.01).结论 AMI患者行急诊PCI治疗可加重体内炎症反应,L-CN能降低PCI术后炎症因子的水平,提示L-CN可能减轻心肌再灌注治疗后的炎症反应.     

Circulating interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and soluble ICAM-1 in patients with chronic stable angina and myocardial infarction

The changes in serum concentrations of cytokines such as interleukin-1 (IL-1) beta, interleukin-6 (IL-6), tumor necrosis factor (TNF) alpha and a soluble-intercellular adhesion molecule (sICAM-1) has been investigated in patients with stable angina and acute myocardial infarction. Thirty-four patients with stable angina (SA), 15 with acute myocardial infarction (AMI), and 20 subjects in the control (C) group were included in the study. The mean serum concentrations of sICAM-1, IL-1-beta, IL-6, and TNF-alpha differed significantly among the three groups. Serum concentrations of IL-1 beta, sICAM-1, and TNF-alpha were comparable in the AMI and SA groups and higher than those found in the C group (p < 0.001). The serum concentration of IL-6 was more than twice as high in the AMI group as compared to the other two groups (p < 0.001). The mean serum concentrations of IL-1 beta, TNF-alpha, and IL-6 were comparable in the AMI and SA groups and higher than in the C group.     

冠心病急性心肌梗死患者血浆心肌营养素-1和血清白介素-18的变化

目的观察冠心病急性心肌梗死（AMI）患者溶栓治疗前后血浆心肌营养素-1（CT-1）和血清白介素-18（IL-18）的变化及意义。方法溶栓组于溶栓即刻,溶栓后2、4、6、8、10、12h测定血中CT-1和IL-18浓度,未溶栓组于症状出现后2、4、6、8、10、12、14h测定血中CT-1和IL-18浓度;同时测定血清cTnI浓度。结果AMI患者IL-18浓度明显高于对照组,升高时间早于cTnI升高的时间（P〈0．01）;AMI患者CT—1水平明显高于对照组,升高时间早于cTnI及IL-18升高的时间（P〈0．01）。与cTnI相比,CT-1和IL-18检测的灵敏度和特异性均较高,尤其是发病早期患者血中尚不能检测到cTnI,而CT-1和IL-18水平即明显升高。②溶栓后4、6、8h,再通组CT—1和IL-18浓度显著高于未再通组（P〈0．01）,未再通组CT-1和IL-18浓度与未溶栓组相比差异无统计学意义。结论@AMI患者血清中很早即可测到较高浓度的cT-1和IL—18,且水平明显高于对照组,时间早于cTnI升高的时间,故认为CT-1和IL-18可作为AMI早期诊断的参考指标之一。②溶栓后4、6、8h,溶栓再通组可检测到明显升高的CT-1和IL-18,故认为CT-1和IL-18可以作为判定AMI溶栓治疗是否再通的指标之一。     

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.     

尿激酶及阿司匹林对血浆α-颗粒膜蛋白140的影响及意义

目的：探讨急性心肌梗塞（ＡＭＩ）患者尿激酶静脉溶栓及阿司匹林口服治疗前后血小板活性的动态变化及与血管再通的关系。方法：８０例ＡＭＩ患者,随机分成溶栓组及溶栓＋阿司匹林组各４０例,于溶栓前及溶栓后２、６、１２、２４小时测定血浆中α－颗粒膜蛋白１４０（ＧＭＰ－１４０）浓度,依临床间接指标（３８例行冠状动脉造影）判定血管再通,比较两组间及两组中再通与未通患者血浆ＧＭＰ－１４０浓度的动态变化。正常对照组６０例。结果：ＡＭＩ患者溶栓前后血浆ＧＭＰ－１４０浓度均明显高于正常对照组。两个溶栓组溶栓后再通与未通患者均呈现不同浓度的动态变化。血管再通,则血浆ＧＭＰ－１４０浓度降低,血管未通,血浆ＧＭＰ－１４０浓度升高;阿司匹林对血浆ＧＭＰ－１４０浓度无影响。结论：ＡＭＩ后血小板高度活化,血浆ＧＭＰ－１４０浓度与血栓形成、溶解及再通密切相关;阿司匹林不是抑制血小板活化的理想药物。     

Increased levels of plasma thrombomodulin in patients with acute myocardial infarction who had thrombolytic therapy and achieved successful reperfusion

BACKGROUND: There is a growing body of evidence from animal and in vitro studies for the existence of reperfusion injury after thrombolytic therapy for acute myocardial infarction (AMI), but the patient data are limited. HYPOTHESIS: We aimed to examine the plasma thrombomodulin (TM) levels as a marker of endothelial injury and to investigate the effect of successful reperfusion on these levels. METHODS: The study included 32 patients who had a first episode of acute myocardial infarction (AMI) and received intravenous streptokinase therapy. RESULTS: Thrombomodulin levels increased significantly at 60 min after thrombolysis compared with the levels before thrombolytic therapy (0 min) in 21 (66%) patients who had successful reperfusion (49.09 +/- 10.51 vs. 25.76 +/- 5.55 ng/ml, p < 0.001). There was no difference between the TM levels at 0 and at 60 min of thrombolysis in the remaining 11 (34%) patients who could not achieve reperfusion (27.81 +/- 6.32 vs. 28.72 +/- 7.28 ng/ml, p = 0.35). CONCLUSION: There was a significant increase in TM levels at 60 min after thrombolysis in a group of patients with AMI who achieved successful reperfusion; this increase may have been caused by the activation/injury of endothelial cells. Data also suggest that the increment in TM levels may be predictive of the potential success of thrombolytic therapy.     

Increased plasma group II phospholipase A(2) concentrations in patients with acute myocardial infarction: correlation with tumor necrosis factor-alpha

AIMS: Group II phospholipase A(2) (PLA(2)) is thought to play an important role in inflammation and tissue injury. It has been suggested that the inflammatory process is important in the setting and progression of myocardial ischemia or reperfusion. We measured plasma PLA(2) as well as inflammatory cytokines in patients in the acute stage of myocardial infarction. METHODS AND RESULTS: In 48 patients with acute myocardial infarction, blood samples were taken to measure plasma PLA(2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) 36-48 h after onset. Serial changes in plasma PLA(2) were also examined in 15 consecutive patients in this group. Plasma PLA(2) levels were significantly higher in complicated patients (Killip's class > or = II) than in uncomplicated patients (Killip's class = I) (35.9 +/- 11.9 vs. 5.3 +/- 1.1 ng/ml, p < 0.01). Plasma PLA(2) concentrations increased gradually over time during the first 3 days and at 36-48 h after onset were correlated with left-ventricular ejection fraction on admission (r = -0.42, p < 0.01), and with plasma TNF-alpha (r = 0.39, p < 0.01), but not with IL-1 beta. CONCLUSION: Plasma PLA(2) concentrations rose during the acute stage of myocardial infarction, especially in severe cases mainly with heart failure. TNF-alpha may be associated with PLA(2)activity as a potent stimulator in vivo.     

急性心肌梗死患者PCI后白介素-6与10的变化及其意义

目的：探讨血白细胞介素-6（IL-6）及IL-10浓度在急性心肌梗死（AMI）患者急诊介入治疗后的变化及其意义。方法：选择60例行急诊经皮冠状动脉介入术（PCI）治疗患者（AMI组）和30例冠状动脉造影正常者（正常对照组）,采用酶联免疫吸附法（ELISA）检测PCI术后第1d及第7d患者的血清IL-6及IL-10的含量,并与正常对照组进行比较分析。结果：与正常对照组相比,AMI组PCI术后患者的血清IL-6[（110.34±26.01）pg/ml比（156.97±68.58）pg/ml]、IL-10[（18.21±4.0）ng/ml比（19.94±10.01）ng/ml]水平及IL-6/IL-10比值[（6.73±2.04）比（10.99±8.24）]明显升高（P〈0.05）,且IL-6与IL-10呈正相关（r=0.44,P〈0.05）;结论：急性心肌梗死后血清白细胞介素-6、白细胞介素-10水平升高,可能参与急性心肌梗死的发生和发展。     

急性心肌梗塞溶栓治疗期间血浆D-二聚体的动态变化及其临床意义

目的 :探讨血浆 D-二聚体对评价溶栓治疗急性心肌梗塞 (AMI)的价值及意义。　　方法 :2 9例 AMI患者分为溶栓组 (n=2 1) ,未溶栓组 (n=8) ;溶栓组根据溶栓治疗后冠状动脉 (冠脉 )是否开通又分为溶栓再通组 (n=12 ) ,溶栓未通组 (n=9) ;采用酶联免疫吸附试验 (EL ISA)法检测血浆 D-二聚体的水平 ,并与正常对照组 (n=2 0 )进行比较。　　结果 :AMI未溶栓组血浆 D-二聚体较正常对照组显著升高 (P<0 .0 5 ) ;溶栓组血浆 D-二聚体较未溶栓组显著升高(P<0 .0 5 ) ,溶栓后血浆 D-二聚体较溶栓前显著升高 (P<0 .0 1) ,于溶栓后 6小时达高峰 ;溶栓再通组血浆 D-二聚体较溶栓未通组显著升高 ,溶栓前及溶栓后 6小时两组比较有极显著统计学意义 (P<0 .0 1)。　　结论 :AMI早期已有纤溶系统亢进 ,应用溶栓药后进一步激活纤溶系统而发挥作用 ,且以溶栓再通组更显著。     

Usefulness of adiponectin to predict myocardial salvage following successful reperfusion in patients with acute myocardial infarction

Adiponectin is an adipose-derived plasma protein that demonstrates beneficial actions on myocardial injury under ischemic conditions. Circulating endothelial progenitor cells are reported to associate with rescue of cardiac damage after acute myocardial infarction (AMI). We examined whether circulating adiponectin level affects myocardial function and injury in patients with AMI. A total of 48 patients who underwent successful reperfusion treatment after AMI were enrolled. Cardiac function and perfusion defect were assessed by scintigraphic images of iodine-123 beta-methyl iodophenyl pentadecanoic acid in the acute phase and technetium-99m tetrofosmin in the long-term phase. Plasma adiponectin levels were measured by enzyme-linked immunosorbent assay at day 7 after AMI. Plasma adiponectin levels associated positively with myocardial salvage index representing the proportion of initial perfusion defect rescued by reperfusion and recovery of ejection fraction in the long-term phase and negatively with final infarct size. A positive correlation was also observed between adiponectin levels and number of circulating CD34(+) cells as determined by flow cytometry and between myocardial salvage index and recovery of ejection fraction independently associated with circulating CD34(+) cell levels. In conclusion, plasma adiponectin levels predict improvement of cardiac damage and function after reperfusion therapy in patients with AMI, suggesting that adiponectin could serve as a biomarker for assessment of myocardial injury after AMI.     

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。     

The effect of high plasma levels of angiotensin-converting enzyme (ACE) and plasminogen activator inhibitor (PAI-1) on the reperfusion after thrombolytic therapy in patients presented with acute myocardial infarction

The resistance to thrombolytic agents and delays in reperfusion occur in more than 30% after acute myocardial infarction. This may play an important role in the unsuccessful recanalization after thrombolytic therapy. The aim of this study is to assess the clinical and biochemical markers of reperfusion after different types of thrombolytic therapy and to find out the relationship between PAI-1 and ACE serum levels and the short-term outcome. Pretreatment ACE and PAI-1 plasma levels of 184 patients with acute myocardial infarction, treated with thrombolytic therapy were determined. Failure of thrombolysis was considered when reperfusion was delayed as assessed by noninvasive reperfusion criteria, reinfarction, and impaired left ventricular function. High plasma level of ACE (> 50 U/L), PAI-1 (> 43 ng/ml) and both was found in 57, 108 and 32 patients respectively. Subjects with high ACE plasma levels were characterized by impaired LV systolic function (79.0% vs. 75.0%), new Q-wave (88.4% vs. 74.2%), less reperfusion arrhythmia (19.3% vs. 22.8%) and prolonged hospitalization (70% vs. 66%) but no statistical significance was observed. High enzymes levels of PAI-1 were observed with higher incidence of anterior myocardial infarction (50.0% vs. 41.0%), lesser ST segment resolution (65.6% vs. 58.8%), reinfarction (6.3% vs. 5.9%), and impaired LV systolic function (90.6% vs. 76.0%), and prolonged hospitalization (70.4% vs. 63.4). There was a statistically significant difference between thrombolytic agents in the presence of high ACE regarding hospital overstay (p = 0.02). While the presence of high PAI-1 was significantly affect the degree of ST-segment resolution (p = 0.03). Conclusion: High plasma ACE and/or PAI-1 plays a considerable role in the higher incidence of unsuccessful reperfusion and impaired left ventricular function after thrombolytic therapy. A rapid diagnostic tool that enables physician of detecting those enzymes before giving thrombolytic therapy may change the strategy of treatment to offer another effective revascularization method.     

Predictive value of plasma interleukin 1, interleukin 6, interleukin 8 and C-reactive protein (CRP) in patients with myocardial infarction

Long-term risk of mortality in patients with myocardial infarction is thought to be linked with plasma concentrations of proinflammatory cytokines and CRP (markers of inflammation). The aim of our study was to analyze plasma levels of interleukin (IL) 1, interleukin 6, interleukin 8 and C-reactive protein (CRP) in patients with myocardial infarction. One hundred and seven (107) patients with myocardial infarction hospitalized at the Cardiac Care Unit of St. Elizabeth's Sisters' Hospital in Warsaw and a control group of 10 subjects were enrolled in our study. The samples of peripheral venous blood were withdrawn from the patients on 2nd and 7th of infarction and plasma levels of IL-1, IL-6, IL-8 and CRP were determined. The patients were followed-up for a year. The analysis of survivals and deaths caused by acute coronary syndrome allowed to determine the predictive value of IL-1, IL-6, IL-8 and CRP in myocardial infarction. Twenty-two (22) of the total 107 patients died of acute coronary syndrome during one-year follow-up. Plasma IL-6 and CRP levels were higher in non-survivors as compared to the levels of IL-6 and CRP in living subjects, whereas plasma levels of IL-1 and IL-8 were comparable in both groups. IL-6 and CRP proved to be of predictive value in patients with myocardial infarction during one-year follow-up. It has also been found that plasma IL-6 level correlates with plasma CRP concentration and that there is a positive correlation between the former and CK-MB levels. IL-6 and CRP levels were higher in patients with Q wave infarction in comparison with non-Q wave infarction. Plasma levels of IL-1 and IL-8 have not been found to be good predictors of death during 12-month follow-up.     

Circulating interleukin-6 and interleukin-6 receptors in patients with acute and recent myocardial infarction

Interleukin-6 (IL-6), a proinflammatory cytokine, plays a key role in the pathogenesis of coronary artery disease (CAD). We investigated circulating IL-6 and its receptors in patients with CAD. We evaluated 39 Japanese patients with CAD (30 males and 9 females aged 36-79 years), measuring their plasma levels of IL-6 and IL-6 receptors alpha and beta (IL-6R alpha, IL-6R beta). Circulating levels of IL-6, IL-6R alpha and IL-6R beta were measured by an enzyme-linked immunosorbent assay. Blood was sampled immediately after admission and again after 1, 2, 3, 6 and 9 h, then every 12 h for 5 days. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) were measured on day 3 after symptom onset. Plasma levels of IL-6 and IL-6Rs were significantly increased in 28 patients with acute myocardial infarction (AMI) compared with 15 normal controls. However, neither IL-6 nor IL-6Rs showed an increase in 6 patients with angina pectoris. We observed two peaks for circulating IL-6 in AMI, the first of which showed a significant correlation with ANP as well as BNP. These results may help to explain why the amount of IL-6 produced is closely related to the severity of myocardial dysfunction in patients with CAD.     

Effects of intravenous sm-9527 (double-chain tissue plasminogen activator) on left ventricular function in the chronic stage of acute myocardial infarction

Clinical effects of thrombolytic agent SM-9527 (double-chain tissue plasminogen activator) on left ventricular (LV) function were assessed in patients with acute myocardial infarction (AMI). A dose of 30 × 10⁶ IU SM-9527 was given intravenously to patients with AMI within 6 h after onset Of 159 candidates, 20 were excluded from the trial due to diseases other than myocardial infarction or failure to meet the protocol requirements; 114 of the remaining 139 were subjected to LV function analysis. The following results were obtained: (1) Patients with successful reperfusion in response to SM-9527 in the acute stage without later reocclusion revealed a significant improvement of LV function in the chronic stage. (2) Adverse effects were noted in 15 patients (10.8%), but none were serious; all were bleeding related to catheterization. (3) Hemagglutination fibrinolysis system test revealed no problems. It is concluded that early thrombolytic therapy with intravenous SM-9527 for AMI provides significant improvement of LV function in the chronic stage.