Adenosine decreases post-ischaemic cardiac TNF-alpha production: anti-inflammatory implications for preconditioning and transplantation.
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.
Meldrum
D R
DR
Department of Surgery, University of Colorado Health Sciences Centre, Denver 80262, USA.
Cain
B S
BS
Cleveland
J C
JC
Meng
X
X
Ayala
A
A
Banerjee
A
A
Harken
A H
AH
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D016027:Heart Transplantation; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D019172:Transplantation Conditioning / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D014409:Tumor Necrosis Factor-alpha; D000241:Adenosine