Anti-tumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion
Anti-tumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion
复制标题
DOI：
10.1016/s0735-1097(97)00328-8
复制
发表时间：
1997-11-15
影响因子：
24
通讯作者：
Mohr, R
中科院分区：
文献类型：
--
作者：
Gurevitch, J;Frolkis, I;Mohr, R
目标.本研究旨在评估局部释放或旁分泌的心肌肿瘤坏死因子α（TNF-α）在缺血后心肌功能障碍的演变中的重要性，并使用免疫组织化学研究定位TNF-α在心肌内。TNF α通过促进白细胞心肌浸润而作为全身介质参与心肌缺血-再灌注损伤的发展，并且已显示其来源于非心脏外周单核细胞。我们最近记录了在无血环境中TNF-α从缺血-再灌注心肌中的释放。采用改良的Langendorff模型，观察了大鼠离体心脏停搏1h后再灌注30 min的情况。将心脏随机分为3组：A组为对照组，B、C组分别接受含抗鼠TNF-α单克隆抗体（B组）和仓鼠IgG（C组）的心脏停搏液。在再灌注1分钟时，在A组和C组流出液中检测到显著量的TNF-α（分别为752 +/- 212和958 +/- 409 pmol/ml）。而在B组，TNF-α低于可检测水平。在该组中，与A组和C组相比，缺血后左心室收缩压峰值、左心室压力上升的一阶导数（dP/dt（max））、压力-时间积分、冠状动脉流量和O-2消耗量均有所改善（所有变量的方差分析[ANOVA] p < 0.0001）;肌酸激酶水平降低（p < 0.005）;心肌结构得以保留。免疫组织化学染色显示TNF-α定位于心肌细胞和内皮细胞。抗TNF-α中和局部TNF-α释放从心肌细胞缺血后，并改善心肌恢复在再灌注过程中，表明缺血后旁分泌TNF-α释放在心肌功能障碍中起着积极的作用。(C)1997年，美国心脏病学会。
Objectives. This study sought to assess the importance of locally released or paracrine myocardial tumor necrosis factor alpha (TNF-alpha) in the evolution of postischemic myocardial dysfunction and to use immunohistochemical studies to localize TNF-alpha within the myocardium.Background. TNF alpha is implicated as a systemic mediator in the development of myocardial ischemia-reperfusion injury by promoting leukocyte myocardial infiltration, and it has been shown to originate from noncardiac peripheral mononuclear cells. We have recently documented in a blood-free environment the release of TNF-alpha from the ischemic-reperfused myocardium.Methods. Isolated rat hearts undergoing 1 h of global cardioplegia-induced ischemia and 30 min of reperfusion mere investigated with use of the modified Langendorff model. Hearts were randomly divided into three subgroups: group A, control group; and groups B and C, isolated hearts receiving cardioplegic solution containing monoclonal hamster antimurine TNF-alpha antibodies (group B) or hamster IgG (group C).Results. Significant amounts of TNF-alpha were detected in group A and group C effluent on 1 min of reperfusion (752 +/- 212 and 958 +/- 409 pmol/ml, respectively). However, in group B, TNF-alpha,vas below detectable levels. In this group, postischemic left ventricular peak systolic pressures, first derivative of the rise in left ventricular pressure (dP/dt(max)), pressure-time integral, coronary flow and O-2 consumption improved (analysis of variance [ANOVA] p < 0.0001 for all variables) compared with values in groups A and C; creatine kinase levels decreased (p < 0.005); and myocardial structure was preserved. Immunohistochemical staining localized TNF-alpha to cardiac myocytes and to endothelial cells.Conclusions. Anti-TNF-alpha neutralizes local TNF-alpha release from cardiac myocytes after ischemia and improves myocardial recovery during reperfusion, indicating that postischemic paracrine TNF-alpha release plays an active role in myocardial dysfunction. (C) 1997 by the American College of Cardiology.