The heart responds to ischaemic stimuli with release of negative inotropic mediators such as cytokines, platelet-activating factor, oxygen free radicals, arachidonic acids, nitric oxide, adenosine, and still unidentified "cardiodepressant factors" that modulate myocardial performance via autocrine and paracrine coupling. This review summarises experimental and clinical data on the role of negative inotropic mediators that are released from cardiac cells (including cardiomyocytes, endothelial cells, and resident mast cells) after myocardial ischaemia-reperfusion. (C) 2002 Elsevier Science B.V. All rights reserved.