Endothelial dysfunction may contribute to the extent of ischaemia/reperfusion injury. ET (endothelin)-1 receptor antagonism protects against myocardial ischaemia/reperfusion injury in animal models. The present study investigated whether oral administration of an ET(A)/ET(B) receptor antagonist protects against ischaemia/reperfusion-induced endothelial dysfunction in humans. FBF (forearm blood ...

INTRODUCTION Ischaemia-reperfusion injury following acute myocardial infarctions (AMI) is an unavoidable consequence of the primary percutaneous coronary intervention (pPCI) procedure. A pivotal mechanism in ischaemia-reperfusion injury is the production of reactive oxygen species following reperfusion. The endogenous hormone, melatonin, works as an antioxidant and could potentially minimise th...

Myocardial protection by pre-conditioning involves increasing the tolerance to ischaemia-reperfusion injury and can be achieved by either mechanical or pharmacological means. Pre-conditioning involves the therapeutic manoeuvre being applied before the start of ischaemia while post-conditioning applies the manoeuvre after the start of ischaemia. The initial method for achieving myocardial protec...

Background: Although the concept of early restoration of coronary bloodflow constitutes an important factor to reduce the injury caused by myocardial ischaemia, reperfusion in itself can aggravate the damage to myocardial tissue, a phenomenon denoted myocardial reperfusion injury. Aims: To investigate whether two different pharmacological interventions, cyclosporine A (CsA) and the novel enkeph...

AIMS Thrombopoietin (Tpo) is known for its ability to stimulate platelet production. However, it is currently unknown whether Tpo plays a physiological function in the heart. METHODS AND RESULTS We assessed the potential protective role of Tpo in vitro and in vivo in two rat models of myocardial ischaemia/reperfusion. Tpo receptor (c-mpl) message was detected in the heart using RT-PCR, and th...

Activation of sphingosine kinase/sphingosine-1-phosphate (SK/S1P)-mediated signalling has been recognized as critical for cardioprotection in response to acute ischaemia/reperfusion injury. Incubation of S1P with cultured cardiac myocytes subjected to hypoxia or treatment of isolated hearts either before ischaemia or at the onset of reperfusion (pharmacologic pre- or postconditioning) results i...

Remote ischaemic preconditioning (RIPC) represents a strategy for harnessing the body's endogenous protective capabilities against the injury incurred by ischaemia and reperfusion. It describes the intriguing phenomenon in which transient non-lethal ischaemia and reperfusion of one organ or tissue confers resistance to a subsequent episode of lethal ischaemia reperfusion injury in a remote orga...

Mitochondria mediate diverse cellular functions including energy generation and ROS (reactive oxygen species) production and contribute to signal transduction. Mitochondria are also key regulators of cell viability and play a central role in necrotic and apoptotic cell death pathways induced by cardiac ischaemia/reperfusion injury. PKC (protein kinase C) ε plays a critical role in cardioprotect...

The current therapeutic strategy for the management of acute myocardial infarction (AMI) is to return blood flow into the occluded coronary artery of the heart, a process defined as reperfusion. However, reperfusion itself can increase mortality rates in AMI patients because of cardiac tissue damage and dysfunction, which is termed 'ischaemia/reperfusion (I/R) injury'. Mitochondria play an impo...