Adenosine decreases post‐ischaemic cardiac TNF‐α production: anti‐inflammatory implications for preconditioning and transplantation

Tumour necrosis factor‐α (TNF‐α) 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‐α. Although adenosine reduces macrophage TNF‐α production and protects myocardium against I/R, it remains unknown whether I/R induces an increase in cardiac TNF‐α in a crystalloid‐perfused model (in the absence of blood), and, whether adenosine decreases cardiac TNF‐α 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‐α (enzyme‐linked immunosorbent assay and bioassay) and function were determined (Langendorff). I/R increased cardiac TNF‐α and impaired myocardial function. Adenosine decreased cardiac TNF‐α and improved post‐ischaemic functional recovery. This study demonstrates that: first, I/R induces an increase in cardiac tissue TNF‐α in a crystalloid‐perfused model; second, adenosine decreases cardiac TNF‐α and improves post‐ischaemic myocardial function; third, decreased cardiac TNF‐α may represent a mechanism by which adenosine protects myocardium; and fourth, adenosine‐induced suppression of cardiac TNF‐α may provide an anti‐inflammatory link to preconditioning and have implications for cardiac allograft preservation.