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.