Tumour necrosis factor mediates E-selectin production and leukocyte accumulation in myocardial ischaemia-reperfusion injury.
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| Abstract |
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.
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| Authors | M Ioculano, D Altavilla, F Squadrito, P Canale, G Squadrito, A Saitta, G M Campo, A P Caputi |
| Journal | Pharmacological research (Pharmacol Res) Vol. 31 Issue 5 Pg. 281-8 (May 1995) ISSN: 1043-6618 [Print] Netherlands |
| PMID | 7479525 (Publication Type: Journal Article) |
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