Parissis John T, Adamopoulos Stamatis, Venetsanou Koula, Kostakis George, Rigas Antonios, Karas Spilios M, Kremastinos Dimitrios
First Department of Cardiology, Amalia Fleming Hospital, Athens Greece.
Eur Cytokine Netw. 2004 Apr-Jun;15(2):139-44.
No in vivo data exist about the relationship of circulating granulocyte-macrophage colony stimulating factor (GM-CSF) and soluble adhesion molecules ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) to the severity of acute myocardial infarction (AMI) and the pathophysiological events of post-infarction left ventricular dysfunction. We investigated the kinetics of these inflammatory mediators in the plasma of patients with AMI, and correlated the findings with the clinical severity of the disease during the first week of hospitalization as well as the degree of left ventricular dysfunction one month after the AMI. Plasma levels of inflammatory markers were determined in 41 AMI patients (all received thrombolytic treatment) by ELISA assays, serially during the first week of hospitalization and one month after hospital admission. Patients (n = 20) with uncomplicated AMI (Killip class I) were classified as group A, patients (n = 21) with AMI complicated by heart failure manifestations (Killip classes II and III) were classified as group B, while 20 age- and sex-matched volunteers were used as healthy controls. A sustained increase in GM-CSF, sICAM-1 and sVCAM-1 plasma concentrations was observed only in group B during the first week of the study. Patients from group B exhibited significantly higher levels of GM-CSF (P < 0.01), sICAM-1 (P < 0.05) and sVCAM-1 (P < 0.01) than patients from group A and the healthy controls (P < 0.001). In group B patients, significant correlations were observed between the peak of GM-CSF levels and the peak of serum creatine kinase-MB (r = 0.42; P < 0.05), white blood cell counts (r = 0.67; P < 0.001) and LVEF (r =- 0.51; P < 0.01). At one month follow-up, patients (n = 17) with severe post-infarction left ventricular dysfunction (LVEF <or=35%) exhibited significantly higher levels of GM-CSF (21.8 +/- 1.5 versus 11.7 +/- 0.9 pg/mL, P < 0.001), sICAM-1 (331.4 +/- 18.4 versus 201.3 +/- 12.1 ng/mL, P < 0.001) and sVCAM-1 (748.4 +/- 34.7 versus 512.9 +/- 18.8 ng/mL, P < 0.001) than did the other patients (n = 24) without this condition (LVEF > 35%). Significant correlations were observed between GM-CSF levels and left ventricular end-diastolic volume index (r = 0.55; P < 0.001) or left ventricular end-systolic volume index (r = 0.49; P = 0.001). We have found a significant elevation of plasma GM-CSF and soluble adhesion molecules during the course of AMI, with the highest values in patients with AMI complicated by heart failure manifestations and severe left ventricular dysfunction. These monocyte-related inflammatory mediators may actively contribute to the pathophysiology of the disease and post-infarction cardiac dysfunction.
关于循环中的粒细胞巨噬细胞集落刺激因子(GM-CSF)以及可溶性黏附分子细胞间黏附分子-1和血管细胞黏附分子-1(sICAM-1和sVCAM-1)与急性心肌梗死(AMI)严重程度及梗死后左心室功能障碍病理生理事件之间的关系,尚无体内研究数据。我们研究了AMI患者血浆中这些炎症介质的动力学变化,并将研究结果与住院第一周疾病的临床严重程度以及AMI后一个月的左心室功能障碍程度进行关联。通过酶联免疫吸附测定法(ELISA),在41例AMI患者(均接受溶栓治疗)住院第一周及入院后一个月期间,连续测定其血浆炎症标志物水平。无并发症的AMI患者(Killip分级I级,n = 20)被归为A组,合并心力衰竭表现的AMI患者(Killip分级II级和III级,n = 21)被归为B组,同时选取20名年龄和性别匹配的志愿者作为健康对照。在研究的第一周,仅在B组中观察到GM-CSF、sICAM-1和sVCAM-1血浆浓度持续升高。B组患者的GM-CSF(P < 0.01)、sICAM-1(P < 0.05)和sVCAM-1(P < 0.01)水平显著高于A组患者及健康对照(P < 0.001)。在B组患者中,观察到GM-CSF水平峰值与血清肌酸激酶-MB峰值(r = 0.42;P < 0.05)、白细胞计数(r = 0.67;P < 0.001)及左心室射血分数(r = -0.51;P < 0.01)之间存在显著相关性。在一个月的随访中,梗死后左心室功能严重障碍(左心室射血分数≤35%,n = 17)的患者,其GM-CSF(21.8 ± 1.5对11.7 ± 0.9 pg/mL,P < 0.001)、sICAM-1(331.4 ± 18.4对201.3 ± 12.1 ng/mL,P < 0.001)和sVCAM-1(748.4 ± 34.7对512.9 ± 18.8 ng/mL,P < 0.001)水平显著高于无此情况(左心室射血分数> 35%,n = 24)的其他患者。观察到GM-CSF水平与左心室舒张末期容积指数(r = 0.