Division of Cardiology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
J Interferon Cytokine Res. 2011 Jun;31(6):509-13. doi: 10.1089/jir.2010.0133. Epub 2011 Feb 20.
Clinical administration of bone marrow-derived stem cells in the setting of acute myocardial infarction (AMI) leads to improved left ventricular ejection fraction. Thymosin beta-4 (TB4) and vascular endothelial growth factor (VEGF) are linked to adult epicardial progenitor cell mobilization and neovascularization and is cardioprotective after myocardial ischemia. This study investigated the time course of TB4 and VEGF during AMI, cardiac arrest, and resuscitation. Fifteen anesthetized and instrumented domestic swine underwent balloon occlusion of the proximal left anterior descending coronary artery. During occlusion, venous blood samples were collected from the right atrium at 5-min intervals until 15 min after the onset of cardiopulmonary resuscitation (CPR). Plasma levels of TB4, VEGF, and matrix metalloproteinase-9 (MMP-9, selected as a marker for remodeling and repair) were measured by ELISA. Generalized linear mixed models were employed to model the time-dependent change in plasma concentration. All variables were natural log transformed, except TB4 values, to normalize distributions. Fifteen animals successfully underwent balloon occlusion of the left anterior descending coronary artery and samples were collected from these subjects. The average onset of spontaneous ventricular fibrillation was 28 min. TB4, VEGF, and MMP-9 demonstrated a statistically significant, time-dependent increase in concentration during ischemia. Following arrest and throughout the first 15 min of resuscitation, MMP-9 had an unchanged rate of rise when compared with the prearrest, ischemic period, with VEGF showing a deceleration in its time-dependent concentration trajectory and TB4 demonstrating an acceleration. Endogenous TB4 and VEGF increase shortly after the onset of AMI and increase through cardiac arrest and resuscitation in parallel to remodeling proteases. These markers continue to rise during successful resuscitation and may represent an endogenous mechanism to recruit undifferentiated stem cells to areas of myocardial injury.
急性心肌梗死（AMI）患者骨髓源性干细胞的临床应用可改善左心室射血分数。胸腺素β-4（TB4）和血管内皮生长因子（VEGF）与成人心外膜祖细胞的动员和新生血管形成有关，在心梗后具有心脏保护作用。本研究旨在探讨 AMI、心脏骤停和复苏过程中 TB4 和 VEGF 的时程变化。15 只麻醉并接受仪器检测的家猪接受了近端左前降支冠状动脉球囊阻塞。在阻塞过程中，每隔 5 分钟从右心房采集静脉血样，直到心肺复苏（CPR）开始后 15 分钟。通过 ELISA 测量 TB4、VEGF 和基质金属蛋白酶-9（MMP-9，作为重塑和修复的标志物）的血浆水平。采用广义线性混合模型来模拟血浆浓度的时间依赖性变化。除 TB4 值外，所有变量均经自然对数转换以正态分布。15 只动物成功进行了左前降支冠状动脉的球囊阻塞，从这些动物中采集了样本。自发性室颤的平均发作时间为 28 分钟。TB4、VEGF 和 MMP-9 在缺血期间呈浓度依赖性显著增加。心脏骤停后，在复苏的前 15 分钟内，MMP-9 的上升速度与心脏骤停前的缺血期相比保持不变，而 VEGF 的时间依赖性浓度轨迹减速，TB4 的上升速度加速。内源性 TB4 和 VEGF 在 AMI 发作后不久增加，并在心脏骤停和复苏过程中与重塑蛋白酶平行增加。这些标志物在成功复苏期间持续升高，可能代表了招募未分化干细胞到心肌损伤区域的内源性机制。
