Elevation of vascular endothelial growth factor-A serum levels following acute myocardial infarction. Evidence for its origin and functional significance

Following the onset of acute myocardial infarction (AMI), a number of serum parameters show well-defined changes reflecting myocardial injury. During the consecutive repair phase, compensatory processes are initiated including the formation of a collateral circulation on the basis of angiogenesis and arteriogenesis. An important angiogenic factor is vascular endothelial growth factor-A (VEGF-A), shown to be upregulated in the ischemic myocardium. It is unclear, however, whether acute myocardial ischemia leads to a detectable elevation of VEGF-A serum concentrations. With the use of an immunoradiometric assay, we measured the levels of VEGF-A in the serum of patients after AMI at defined time intervals, of patients with unstable angina pectoris (UAP) and of healthy individuals. In addition, in a small group of patients with subacute myocardial infarction VEGF-A concentrations were measured in coronary sinus blood. The data are given as median followed by the 25th and 75th percentiles. In the group with AMI serum VEGF-A measured 105 [78; 176] pg/ml on day 1 and 114 pg/ml [72; 163] pg/ml on day 3 after onset of AMI. Serum levels of VEGF-A significantly increased on day 7 after AMI to 189 [119; 373] pg/ml (P=0.0103) and on day 10 to 255 [162; 371] pg/ml (P=0.0007). The VEGF-A serum level in healthy controls and in patients with UAP measured 98 [75; 137] pg/ml and 116 [57; 140] pg/ml, respectively. Serum at day 10 after AMI contained VEGF-A at a biologically relevant concentration capable of stimulating proliferation of endothelial cells. Surprisingly, VEGF-A serum levels were similar in samples taken from the coronary sinus with 61 [43; 83] pg/ml. Therefore the main source for VEGF-A in the blood stream is not the infarcted myocardium. However, the number of platelets, a rich source of VEGF-A, is significantly increased after myocardial infarction, i.e. 284 [252; 363] x 10(9)/litre v 220 [177; 250] x 10(9)/litre. In conclusion, the time course of VEGF-A elevation following AMI strongly suggests that VEGF-A plays a role as an endogenous activator of coronary collateral formation in the human heart. The most likely source of the elevated VEGF-A are platelets, rather than the infarcted myocardium.     

冠心病患者血清C反应蛋白和可溶性细胞间粘附分子1与肺炎衣原体感染的相关性

目的探讨冠心病患者血清炎症标志物C反应蛋白和可溶性细胞间粘附分子1水平的变化及其与肺炎衣原体感染的关系。方法采用酶联免疫吸附法检测60例急性心肌梗死、不稳定型心绞痛、陈旧性心肌梗死、稳定型心绞痛及40例对照者血清C反应蛋白、可溶性细胞间粘附分子1及肺炎衣原体抗体IgG、IgM。结果冠心病组肺炎衣原体IgG阳性率和浓度均高于对照组(P<0.01),冠心病各组之间肺炎衣原体IgG和IgM阳性率差异无显著性(P>0.05),急性心肌梗死组肺炎衣原体IgG浓度高于陈旧性心肌梗死组、不稳定型心绞痛组和稳定型心绞痛组(P<0.05);冠心病组C反应蛋白、可溶性细胞间粘附分子1水平高于对照组(P<0.01),急性心肌梗死组C反应蛋白、可溶性细胞间粘附分子1水平高于不稳定型心绞痛组、陈旧性心肌梗死组和稳定型心绞痛组(P<0.01),不稳定型心绞痛组C反应蛋白、可溶性细胞间粘附分子1水平高于稳定型心绞痛组(P<0.05);肺炎衣原体IgG浓度、C反应蛋白、可溶性细胞间粘附分子1之间有很好的相关性(P<0.05)。结论炎症标志物水平变化在一定程度上反映了冠心病患者病情变化,肺炎衣原体感染与冠心病有关,炎症、感染可能共同参与了冠心病的发生发展。     

Hepatocyte growth factor production may be related to the inflammatory response in patients with acute myocardial infarction.

Hepatocyte growth factor (HGF) is a well-known powerful proliferative factor of vascular endothelial cells and it has been reported that plasma HGF concentrations are increased in acute myocardial infarction (AMI), although the mechanisms are not yet well delineated. Serum HGF levels and C-reactive protein (CRP) were measured in 22 patients with unstable angina pectoris (UAP) (15 males, 7 females; class IIb or IIIb of the Braunwald classification), 60 patients with AMI (37 males, 23 females; average time from the onset of symptoms to admission 4.6+/-0.7h, range, 0.5-12h), and 20 normal subjects. Immediate angioplasties were performed in 51 patients with AMI, and the time course of the HGF levels were measured in 31 patients among them. Heparin dramatically increased the HGF level and it declined to the normal range 18h after heparin injection. Blood samples were taken before heparin treatment, or at least 24h after. Serum HGF levels on admission was significantly increased in UAP (mean+/-SE: 0.30+/-0.03ng/ml, p<0.01), and AMI (0.27+/-0.02ng/ml, p<0.01) compared with the normal subjects (0.19+/-0.01 ng/ml). Even in the early stage (within 3 h of onset of symptoms to admission, average time was 1.8+/-0.1 h), serum HGF levels were already elevated (0.25+/-0.02 ng/ml, p<0.05). There was no significant difference between the HGF levels in UAP and AMI. Fifty-one of the 60 patients with AMI underwent immediate percutaneous transluminal coronary angioplasty and blood samples were obtained from 31 of them on days 7, 14, and 21 after MI. Serum HGF levels peaked on day 7 (0.34+/-0.04ng/ml, p<0.01) and there was a weak relationship between peak creatine kinase and serum HGF levels at that time. A statistically significant correlation was found between peak CRP and serum HGF levels on day 7 (r=0.62: p<0.001). Serum HGF levels decreased to nearly normal by day 21 (0.22+/-0.01 ng/ml). The study shows that serum HGF levels during the early stage of AMI increased significantly and peaked by day 7 after the onset, at which time there was a strong correlation with peak CRP levels. These data suggest that HGF production may be related to the inflammatory response in AMI.     

Usefulness of high-sensitivity C-reactive protein in predicting long-term risk of death or acute myocardial infarction in patients with unstable or stable angina pectoris or acute myocardial infarction.

High-sensitivity C-reactive protein (CRP), proposed as a new coronary risk marker, may reflect either an acute phase reaction or the level of chronic inflammation. Thus, CRP may be less predictive of long-term outcomes when measured after acute myocardial infarction (AMI) than after unstable angina pectoris (UAP) or stable angina pectoris (SAP). A total of 1,360 patients with severe coronary artery disease (>/=1 stenosis >/=70%) had CRP levels obtained at angiography. Presenting diagnoses were SAP (n = 599), UAP (n = 442), or AMI (n = 319). During follow-up (mean 2.8 years), death or nonfatal AMI (D/AMI) occurred in 19.5%, 16.1%, and 17.2% (p = NS) with SAP, UAP, and AMI, respectively. Corresponding median CRP levels were 1.31, 1.27, and 2.50 mg/dl (p <0.001). For the overall cohort, increasing age, low ejection fraction, revascularization, and elevated CRP were the strongest of 6 independent predictors for D/AMI. Among those presenting with SAP, CRP levels above the first tertile were associated with an adjusted hazard ratio of 1.8 (95% confidence interval [CI] 1.2 to 2.8, p <0.009) for D/AMI. After UAP, the hazard ratio was 2.7 (95% CI 1.4 to 5.0, p <0.002). However, when measured during hospitalization for AMI, CRP was not predictive of long-term outcome (hazard ratio 1.0 [95 % CI 0.5 to 1.7] p = 0.86). In conclusion, predischarge CRP levels are higher after AMI than after UAP or SAP. However, whereas CRP is strongly predictive of long-term D/AMI for patients presenting with SAP or UAP, it is not predictive shortly after AMI, suggesting that measurements should be delayed until the acute phase reaction is over and levels have returned to baseline.     

Association of C-reactive protein and myocardial perfusion in patients with ST-elevation acute myocardial infarction

This study sought to evaluate the relation between C-reactive protein (CRP) on admission of patients with acute myocardial infarction (AMI) and myocardial perfusion as defined by postintervention angiographic myocardial blush grade (MBG) and their impact on subsequent mortality. The patient population comprised 191 consecutive patients with AMI undergoing PTCA within 12h of symptom onset on a native vessel. Patients were divided based on the CRP level on admission (Rolf Greiner BioChemica, Germany, cutpoint for the assay CRP: 5mg/l) into a group with elevated CRP (>or=5mg/l) and a group with normal CRP. Angiographic myocardial blush grade (MBG) after revascularization of the infarct-related artery was determined to evaluate myocardial reperfusion. Revascularization of the infarct-related artery was successful in 176 (92.6%) patients. The frequency of impaired perfusion (MBG 0-2) was higher in the elevated CRP group than in the normal CRP group (74.5% versus 59.7%, respectively, p=0.046). Elevated CRP on admission was an independent predictor of impaired myocardial perfusion (MBG 0-2, OR 1.92, 95% CI 1.02-4.01, p=0.042) in addition to age >70 years. Elevated CRP (OR 2.64, 95% CI 1.26-5.53, p=0.009) and MBG 0-2 (OR 4.58; 95% 1.73-12.20, p=0.002) were independent predictors of mortality during a 22.4+/-15.3 months follow-up in addition to heart rate on admission >100 beats/min (OR 3.07; 95% CI 1.30-7.25, p=0.009). In sequential Cox models, the predictive power of clinical data and MBG for mortality (model chi-squared 18.3) was strengthened by the inclusion of CRP levels (model chi-squared 24.3). In conclusion, there is a relation between elevated admission CRP and impaired reperfusion in the myocardium subtended to the infarct-related artery. The combination of clinical data, myocardial reperfusion levels after primary angioplasty for AMI and admission CRP increases the predictive value for subsequent survival.     

血清C-反应蛋白对不稳定型心绞痛患者预后的预测价值

目的　探讨不稳定型心绞痛(UAP)患者血清C -反应蛋白(CRP)水平与心血管事件发生的关系。方法　将UAP患者按入院2 4小时内血清CRP水平分为两组:低CRP组(CRP <3 .5mg·L-1) 4 6例,高CRP组(CRP≥3. 5mg·L-1) 5 8例。两组患者入院后均予常规内科治疗,比较2周内及随访6个月时两组发生心血管事件的情况。结果　(1)低CRP组2周内发生心绞痛总数次15 8例次,平均3 .4 3次/人,与高CRP组总2 86例次,平均4 .93次/人比较有显著性差异(P <0 . 0 5 ) ;随访6个月时,低CRP组共发生心绞痛2 0 1例次,平均4 .37次/人,与高CRP组总76 3例次,平均13. 1次/人比较有显著性差异(P <0 . 0 1) ;(2 )低CRP组2周内及随访6个月时发生急性心肌梗死(AMI)例数(% )分别为6例(13 .0 % )及2例(4 .4 % )与高CRP组18例(31 .0 % )及13例(2 2. 4 % )比较有显著性差异(P <0 . 0 5 ) ;(3)低CRP组随访6个月时发生猝死1例(2 . 2 % )与高CRP组5例(8. 6 % )比较无显著性差异(P >0 . 0 5 )。结论　血清CRP水平对UAP患者近远期心血管事件的发生有很高的预测价值。     

急性心肌梗死发病6 h内C反应蛋白的检测及其临床意义

目的　探讨急性心肌梗死 (AMI)患者发病 6h内C反应蛋白 (CRP)变化的临床意义。方法　测定 2 17例AMI患者发病 6h内的血浆CRP浓度。将患者分为CRP增高组和CRP正常组。所有患者均予介入性治疗。结果　不利的冠状动脉事件 (包括冠状动脉闭塞、再梗死和死亡 ) ,CRP增高组 ( 32 .6 % )较CRP正常组 ( 4 .7% )显著增加 (P <0 .0 1)。两组之间心肌损伤的参数(包括肌酸磷酸激酶高峰和左心室射血功能 )比较差异无显著性。结论　AMI发病 6h内CRP水平反应出冠脉损伤的易患性 ,可预见经皮穿刺冠状动脉成形术 (PTCA) /支架后不利的冠状动脉事件。     

急性心肌梗塞发生中肿瘤坏死因子的作用探讨

本文观察了22例AMI患者及免心便模型血浆中TNF的含量变化，以研究TNF对心肌梗塞坏死面积的影响。结果发现：（1）AMI患者心肌梗塞早期血浆TNFα迅速升高，高峰在胸痛发作后4小时，显著高于正常对照组（P＜0．001），以后逐渐下降，48小时与正常对照组比较无差异（P＞0．05）。（2）在免心梗模型中，用TNF单克隆抗体中和血浆中的TNF后，坏死区占缺血区和坏死区占左心室的体积百分比ATM组显著低于AMI组（P＜0．01）。提示：TNFα在AMI发生中起重要作用，TNFα单克隆抗体可显著减少心肌梗塞范围。     

Prognostic value and the changes of plasma levels of secretory type II phospholipase A2 in patients with coronary artery disease undergoing percutaneous coronary intervention.

AIM: To evaluate the serial changes of plasma secretory type II phospholipase A(2)(sPLA(2)), C-reactive protein (CRP) and cardiac injury markers in coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) and their prognostic impacts. METHODS AND RESULTS: Plasma levels of sPLA(2), CRP, creatine kinase (CK), CK-MB and troponin-T were measured in 247 consecutive CAD patients receiving PCI procedure and 100 control subjects without CAD. In CAD group, serial blood samples were taken before coronary angiography, after coronary angiography, immediately after PCI, 24-h and 48-h after PCI. The sPLA(2)and CRP levels did not change after coronary angiography. The level of sPLA(2)significantly increased immediately after PCI. Creatine kinase and cardiac injury markers did not rise immediately after PCI, but elevated significantly at 24h after intervention. After a 2-year follow up, increased sPLA(2)(>450 ng/dl) after PCI, smoking and diabetes mellitus were the independent risk factors for subsequent coronary events (odds ratios 2.1, 2.3 and 3.1, respectively) in patients with CAD. CONCLUSION: The present study showed that PCI might cause immediate elevation of circulating levels of sPLA(2)following the mechanical disruption of coronary plaque, and the elevated level of sPLA(2)had significant prognostic impact.     

Prognostic value of C-reactive protein levels within six hours after the onset of acute myocardial infarction

BACKGROUND: Inflammation is an important feature of atherosclerotic lesions, and the vulnerability of coronary lesions in acute myocardial infarction (AMI) at the time of onset may be related to blood levels of C-reactive protein (CRP) on admission, before CRP levels are affected by myocardial damage. METHODS: A total of 234 patients with AMI in whom plasma CRP was measured within 6 hours after onset were studied. They were divided into 2 groups: group 1 (n = 49) with elevated CRP (>/=0.3 mg/dL) on admission within 6 hours after onset and group 2 (n = 185) with normal CRP (<0.3 mg/dL) within 6 hours after onset. All were treated by primary percutaneous transluminal coronary angioplasty with provisional stenting. RESULTS: There were no significant differences in baseline characteristics between the 2 groups. In-hospital adverse coronary events, including coronary reocclusion, reinfarction, target vessel revascularization, and death, were significantly more frequent in group 1 (22.4%) than in group 2 (4.3%, P <.005), and bailout stenting was performed significantly more frequently in group 1 (61. 2%) than in group 2 (37.8%, P <.005). In contrast, there were no significant differences between the 2 groups in parameters that represent myocardial damage, including peak creatine kinase and left ventricular ejection fraction. CONCLUSION: CRP levels within 6 hours after the onset of AMI reflect the vulnerability of culprit coronary lesions and predict adverse coronary events after primary PTCA/stenting.     

cTnT在判断急性心肌梗死及不稳定型心绞痛预后中的价值

目的 :探讨心肌肌钙蛋白 T（c Tn T）对急性心肌梗死 （AMI）诊断及评估不稳定型心绞痛 （U AP）预后的临床价值。方法 :对 76例胸痛患者进行入院即刻血浆 c Tn T半定量、同步心肌酶学定量测定 ,观察对比 c Tn T与心肌酶学在诊断 AMI及评估 U AP患者预后中的特异性和敏感性。结果 :76例胸痛患者中 AMI 34例、U AP 2 7例、稳定劳力性心绞痛 8例、其它胸痛疾患 7例。AMI34例 c Tn T全部阳性 ,而 U AP2 3例和其余病例 c Tn T均为阴性。AMI患者同步 CK,AST升高者 2 8例 ,L DH升高者 30例。c Tn T与心肌酶学差异未达显著水平 （P>0 .0 5 ） ,但发病 2～ 5 h者 10例 ,心肌酶各项均正常 ,与 c Tn T对比有高度显著性差异 （P<0 .0 1） ;发病 5～ 11d者 6例 ,仅 2例 L DH还表现出升高外 ,其余心肌酶均正常 ,与 c Tn T对比有显著性差异 （P<0 .0 5 ） ;发病 5～ 12 0 h者相差均不显著 （P>0 .0 5 ）。在 2 7例 U AP患者中 ,c Tn T阳性组 AMI和难治性心绞痛发生率显著高于 c Tn T阴性组 （P<0 .0 1） ;c Tn T阴性组药物疗效好 ,近期心脏事件发生率低 ,与 c Tn T阳性组对比亦有高度显著性差异 （P<0 .0 1）。结论 :c Tn T是反映心肌细胞损伤灵敏性、特异性均较好的生化指标 ;c Tn T对诊断早期和晚期 AMI的价值高于心肌酶学 ;c Tn T阳性     

A strategy of retrograde injection of bone marrow mononuclear cells into the myocardium for the treatment of ischemic heart disease

OBJECTIVE: Bone marrow cells implantation (BMI) has been reported to efficiently improve ischemic heart disease. However, BMI strategies are generally invasive. To establish a BMI strategy for ischemic heart disease, we performed implantation of autologous cryopreserved mononuclear cells (MNCs) from bone marrow (BM) retrogradely into the myocardium via the coronary vein in pigs with acute myocardial infarction (AMI) and old myocardial infarction (OMI). METHODS: BM cells were harvested from the pigs' fumurs. MNCs were collected by centrifugation and were cryopreserved. Anterior myocardial infarction was induced by occlusion of the midportion of the left anterior descending coronary artery without surgical intervention. Frozen BM cells were quickly thawed and injected retrogradely via the coronary vein into the myocardium through a single balloon infusion catheter 6 h and 2 weeks after the induction of infarction. Four weeks after implantation, coronary arteriograms were obtained, cardiac function was analyzed with the use of a conductance catheter, and histopathologic analysis was performed with a confocal laser microscope. Plasma levels of natriuretic peptides and angiogenic growth factors were measured after BMI. RESULTS: Flow cytometric analysis revealed that 90% of cryopreserved BM cells were viable in vitro. Labeled BM cells were entirely distributed around in the infarcted area of maycardium in pigs. BMI increased collateral neovascuralization in infarcted hearts. BMI significantly improved cardiac function in AMI with BMI and OMI with BMI groups. BMI also increased the formation of microcapillary arteries in infarcted hearts. Levels of natriuretic peptides were significantly decreased, and levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) were significantly increased after BMI. Confocal laser microscopy revealed the presence of proliferative and activated myocardial cells in infarcted hearts after BMI. CONCLUSION: The retrograde infusion of cryopreserved BM cells into myocardium efficiently induced angiogenesis and improved cardiac function in pigs with AMI or OMI. These results suggest that the present strategy of BMI will be safe and feasible as an angiogenic cell therapy for ischemic heart disease.     

Improved detection of acute myocardial infarction by magnetic resonance imaging using Gadolinium-DTPA

Summary To assess the value of the paramagnetic contrast agent Gadolinium (Gd)-DTPA in Magnetic Resonance Imaging (MRI) of acute myocardial infarction (AMI), we studied 20 patients with a first AMI by ECG-gated MRI before and after intravenous administration of 0.15mmol/kg Gd-DTPA. The MRI studies were performed after a mean of 98 hours (range 15–241) after the acute onset of AMI. Spin-echo measurements (TE 30 msec) were made using a Philips Gyroscan (0.5 Tesla). After performing the baseline MRI scans, the MRI procedure was repeated every 10 minutes for up to 40 minutes following injection of Gd-DTPA. In 18 (90%) patients contrast enhancement in the infarcted myocardial areas was observed after Gd-DTPA. In these patients intensity versus region curves, derived from 9 to 11 adjacent myocardial regions of interest, showed increased signal intensities in the infarcted areas after administration of Gd-DTPA. The precontrast signal intensity ratio between infarcted and normal myocardium was 1.14±0.15 (mean±SD); the postcontrast ratios at 10 minutes were 1.41±0.21 (P <0.05), at 20 minutes 1.61±0.19 (P <0.01), at 30 minutes 1.43±0.20 (P < 0.05), and at 40 minutes 1.33±0.20 (P=NS). It is concluded that MRI using the contrast agent Gd-DTPA significantly improves the visualization and detection of infarcted myocardial areas in patients with AMI and that optimal contrast enhancement is obtained 20 minutes after administration of Gd-DTPA.     

急性冠状动脉综合征患者血清炎性细胞因子水平及临床意义

目的通过对急性冠状动脉综合征患者血清炎性细胞因子水平的测定及比较,分析炎症及细胞因子在急性冠状动脉综合征发生发展过程中的作用及临床意义。方法选择急性心肌梗死(AMI)患者44例(AMI组),不稳定性心绞痛(UAP)患者44例(UAP组),稳定性心绞痛(SAP)患者43例(SAP组),无冠心病患者35例(对照组),分别检测各组患者血清白细胞介素6(IL-6)、白细胞介素8(IL-8)、白细胞介素10(IL-10)、TNF-α、C反应蛋白(CRP)和基质金属蛋白酶9(MMP-9)浓度并进行比较。结果 AMI组患者血清IL-6、IL-8、IL-10、TNF-α、CRP和MMP-9水平均明显高于SAP组和对照组(P<0.01);AMI组患者血清IL-10、TNF-α、CRP、MMP-9水平明显高于UAP组(P<0.05);UAP组患者血清IL-6、IL-8、IL-10水平明显高于SAP组和对照组;MMP-9和CRP与IL-6呈正相关(r=0.308,r=0.384,P<0.01)。结论冠心痛与炎性反应密切相关,多种细胞因子参与了动脉粥样硬化斑块的形成和进程,血清炎性细胞因子水平的升高是冠状动脉粥样硬化斑块不稳定的标志。     

急性心肌梗死和不稳定性心绞痛患者粘附分子及相关因素的研究

目的　探讨急性心肌梗死 (AMI)和不稳定性心绞痛 (UAP)患者发病早期和 1周可溶性细胞间粘附分子 1(sICAM 1)、可溶性血管细胞粘附分子 1(sVCAM 1)、D 二聚体、血小板第 4因子 (PF4 )的动态变化及其相互关系。方法　测定 40例AMI、45例UAP患者发病 2 4h和 1周时血清sICAM 1、sVCAM 1、D 二聚体、PF4 并与 30例对照组比较。结果　AMI和UAP患者于发病 2 4h和 1周时sICAM 1、sVCAM 1、D 二聚体、PF4 均明显高于对照组 (P<0 0 1)。AMI组中 ,溶栓再通者与未溶栓者sICAM 1、sVCAM 1、D 二聚体、PF4 比较 ,差异无显著性意义 (P>0 0 5 )。AMI溶栓组中再通后与再通前相比 ,sICAM 1、sVCAM 1、D 二聚体均明显下降 (P <0 0 5 ) ;AMI、UAP组于发病 2 4h及 1周时sICAM 1与sVCAM 1均具有正相关性 (P <0 0 1) ,PF4 与sICAM 1、sVCAM 1、D 二聚体间亦具有正相关性 (P <0 0 1)。结论　AMI、UAP从发病早期至 1周sICAM 1、sVCAM 1持续升高 ,以AMI更为明显 ,表明炎症参与心肌细胞损伤过程     

Changes in serum interleukin-8 and interleukin-12 levels in patients with ischemic heart disease in a Chinese population.

Increasing evidence has indicated the important roles of inflammation and immune response in the development of atherosclerosis and ischemic heart disease (IHD). We measured the serum interleukin (IL)-8 and IL-12 levels of patients with unstable angina pectoris (UAP) and patients with acute myocardial infarction (AMI), and compared findings with those of normal subjects. The results showed that the serum level of IL-8 was significantly higher in patients with UAP and patients with AMI than in healthy control subjects. To our knowledge, this is the first report that serum IL-12 level was elevated in patients with AMI but not in patients with UAP. These findings suggest that IL-8 and IL-12 are involved in the process of IHD, and serum IL-12 may be a marker for differentiating AMI from UAP.     

Kinetics of tumor necrosis factor alpha in plasma and the cardioprotective effect of a monoclonal antibody to tumor necrosis factor alpha in acute myocardial infarction.

BACKGROUND: Inflammation plays a critical role in acute myocardial infarction (AMI) and tumor necrosis factor alpha (TNF-alpha) is a potent inflammatory trigger. This study was designed to examine the kinetics of TNF-alpha in plasma in patients with AMI and the potential benefit of inhibition of TNF-alpha monoclonal antibody in AMI. METHODS AND RESULTS: TNF-alpha levels in plasma were measured in 42 patients with AMI. TNF-alpha levels were elevated at 4 hours after onset of chest pain and declined to control values at 48 hours. TNF-alpha levels were higher in patients with Killip III and IV than in those with Killip I and II (P <.01). To examine the pathogenic role of TNF-alpha, New Zealand White rabbits were treated with buffer or a TNF-alpha monoclonal antibody before left anterior descending artery (LAD) ligation. Treatment with the TNF-alpha monoclonal antibody decreased area of necrosis, number of circulating endothelial cells, and lipid peroxidation product malonaldehyde bis(dimethyl acetal). There was a significant correlation of TNF-alpha levels with peak CK-MB in AMI patients, and area of necrosis, MDA, and circulating endothelial cells in rabbits (all P <.05). CONCLUSIONS: TNF-alpha release early in the course of AMI contributes to myocardial injury and dysfunction. Treatment with the monoclonal antibody against TNF-alpha can be cardioprotective, particularly in the setting of heart failure in patients with AMI.     

Graphical comparison of coronary arterial culprit lesions in acute myocardial infarction and unstable angina pectoris

OBJECTIVE: The culprit lesion morphology at acute myocardial infarction (AMI) and unstable angina pectoris (UAP) was investigated by observing the responsible vessels through intravascular ultrasound (IVUS) during the acute stage. METHODS: As the subjects of study, 54 lesions of 54 ACS patients (26 in AMI patients, 28 in UAP patients) were enrolled prospectively from June 1994 to June 1998. The appearance of plaque in the lesion, the distal and proximal sites, extent of calcification, eccentricity, remodeling and shrinkage were observed through IVUS before the intervention. RESULTS: At lesion and distal site, significantly more soft plaques were observed in AMI than UAP. As to the extent of calcification in the former, mild calcification was noted significantly more in distal site as well as a tendency of more mild calcification in the lesion and proximal site. CONCLUSION: These results suggested that the condition of responsible coronary artery is involved in the onset mechanism of AMI and UAP.     

Simultaneous development of acute phase response and autoantibodies in preclinical rheumatoid arthritis

OBJECTIVE: To investigate the temporal relationship between onset of inflammation (as measured by secretory phospholipase A2 (sPLA2) and C reactive protein (CRP)) and the presence of autoantibodies (IgM rheumatoid factor (IgM RF) and antibodies against citrullinated peptides (anti-CCP)) in the preclinical phase of rheumatoid arthritis (RA). METHODS: For 79 patients with RA who had been blood donors before the onset of disease, a median of 13 serum samples per patient was available. sPLA2 was measured in patient and matched control samples and related to previous CRP, IgM RF, and anti-CCP measurements. The temporal relationship between the increased markers of inflammation and autoantibodies was analysed with time lag analysis. RESULTS: IgM RF and anti-CCP concentrations were significantly associated (p<0.001) with concentrations of sPLA2, CRP, and the combination of sPLA2 and CRP at the same time point. However, we found no stronger association between the two autoantibody tests and the three inflammation measures 1, 2, and 3 years before or after a time point than for measurements at the same time, in the whole group or in subgroups of IgM RF and anti-CCP positive patients. CONCLUSION: Both the acute phase response and autoantibody formation often develop years before the first symptoms of RA occur, and these phenomena are probably closely connected in time.     

PCI术后AMI患者非梗死区冠脉血流储备的变化及其对左室功能的影响

目的 观察和分析急性心肌梗死（AMI）患者PCI术后非梗死区冠脉血流储备（CFR）的变化及其对左室功能的影响。方法 22名AMI患者PCI术后1周行二维超声心动图和多巴酚丁胺负荷实时心肌声学造影（MCE）检查,测量左室功能和梗死区、非梗死区CFR,比较非梗死区CFR与梗死区及正常对照组CFR;根据非梗死区CFR值将患者分为两组,比较两组远期左室功能的变化。结果 非梗死区CFR值与正常对照组相比明显下降,非梗死区CFR与左室舒张末期容积呈负相关。结论 AMI后非梗死区心肌同样存在微循环功能障碍,非梗死区CFR值能预测AMI后远期左室功能。