Tumour necrosis factor mediates E-selectin production and leukocyte accumulation in myocardial ischaemia-reperfusion injury.
The aim of our study was to examine the mechanism of E-selectin production and leukocyte accumulation in myocardial ischaemia-reperfusion injury. Myocardial injury was induced in anaesthetized rats by the clamping of the left main coronary artery followed by reperfusion. After thoracotomy a silk suture was placed under the left coronary artery. The ligature was tied for a period of 1 h and after this period it was untied and the ischaemic myocardium was reperfused for 1 h (MI/R rats) or removed (SHAM MI/R rats). Myocardial ischaemia plus reperfusion in untreated rats decreased survival rate, produced a marked myocardial necrosis, enhanced cardiac myeloperoxidase activity (a marker enzyme commonly used to assess polymorphonuclear leukocyte infiltration) and increased serum creatinephosphokinase (CPK) activity, serum levels of tumour necrosis factor-alpha (TNF-alpha) and serum levels of soluble E-selectin (sE-selectin). Furthermore, MI/R rats had an increased pressure rate index studied as a quantitative means for assessing myocardial oxygen demand. Administration of cloricromene, an inhibitor of TNF-alpha, reduced TNF-alpha production, significantly lowered serum sE-selectin levels, blunted leukocyte accumulation in the ischaemic myocardium and protected the myocardium from injury due to ischaemia and reperfusion. The results of the present study show an involvement of E-selectin in vivo in the pathogenesis of myocardial ischaemia and reperfusion and suggest that TNF-alpha may induce in vivo the production of a specific adhesion mechanism which sustains leukocyte infiltration.
D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha