Meldrum D R, Cain B S, Cleveland J C, Meng X, Ayala A, Banerjee A, Harken A H
Department of Surgery, University of Colorado Health Sciences Centre, Denver 80262, USA.
Immunology. 1997 Dec;92(4):472-7. doi: 10.1046/j.1365-2567.1997.00380.x.
Tumour necrosis factor-alpha (TNF-alpha) is an autocrine contributor to myocardial dysfunction and cardiomyocyte death in ischaemia-reperfusion injury (I/R), sepsis, chronic heart failure and cardiac allograft rejection. Cardiac resident macrophages, infiltrating leucocytes, and cardiomyocytes themselves produce TNF-alpha. Although adenosine reduces macrophage TNF-alpha production and protects myocardium against I/R, it remains unknown whether I/R induces an increase in cardiac TNF-alpha in a crystalloid-perfused model (in the absence of blood), and, whether adenosine decreases cardiac TNF-alpha and protects function after I/R. To study this, isolated rat hearts were crystalloid-perfused using the Langendorff method and subjected to I/R, with or without adenosine pretreatment. Post-ischaemic cardiac TNF-alpha (enzyme-linked immunosorbent assay and bioassay) and function were determined (Langendorff). I/R increased cardiac TNF-alpha and impaired myocardial function. Adenosine decreased cardiac TNF-alpha and improved post-ischaemic functional recovery. This study demonstrates that: first, I/R induces an increase in cardiac tissue TNF-alpha in a crystalloid-perfused model: second, adenosine decreases cardiac TNF-alpha and improves post-ischaemic myocardial function; third, decreased cardiac TNF-alpha may represent a mechanism by which adenosine protects myocardium; and fourth, adenosine-induced suppression of cardiac TNF-alpha may provide an anti-inflammatory link to preconditioning and have implications for cardiac allograft preservation.
肿瘤坏死因子-α（TNF-α）在缺血再灌注损伤（I/R）、脓毒症、慢性心力衰竭及心脏移植排斥反应中，是导致心肌功能障碍和心肌细胞死亡的自分泌因素。心脏固有巨噬细胞、浸润的白细胞以及心肌细胞自身均可产生TNF-α。尽管腺苷可减少巨噬细胞TNF-α的产生，并保护心肌免受I/R损伤，但在晶体液灌注模型（无血液）中I/R是否会导致心脏TNF-α增加，以及腺苷在I/R后是否会降低心脏TNF-α并保护心脏功能，目前仍不清楚。为研究这一问题，采用Langendorff方法对离体大鼠心脏进行晶体液灌注，并使其经历I/R，同时进行或不进行腺苷预处理。测定缺血后心脏TNF-α（酶联免疫吸附测定和生物测定）及心脏功能（Langendorff法）。I/R增加了心脏TNF-α水平并损害了心肌功能。腺苷降低了心脏TNF-α水平并改善了缺血后的功能恢复。本研究表明：第一，在晶体液灌注模型中I/R可导致心脏组织TNF-α增加；第二，腺苷可降低心脏TNF-α水平并改善缺血后心肌功能；第三，心脏TNF-α水平降低可能是腺苷保护心肌的一种机制；第四，腺苷诱导的心脏TNF-α抑制可能为预处理提供抗炎联系，并对心脏移植保存具有重要意义。
