Pharmacological interventions against myocardial ischaemia and reperfusion injury

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 enkephalin analogue EP 94, could confer cardioprotection in porcine models of myocardial ischaemia and reperfusion. Furthermore, to examine the distribution of the opioid receptor subtypes in the porcine heart, and to investigate how this expression is affected by ischaemia and reperfusion. Methods: Anesthetised pigs underwent balloon occlusion of the left anterior descending coronary artery, followed by reperfusion. CsA and EP 94 were administered at reperfusion and hearts stained to measure infarct size. mRNA and protein expression of pro-apoptotic proteins, endothelial NO-synthetase and opioid receptor subtypes was quantified in the control and ischaemic/reperfused areas. Results: Two different dosages of CsA did not confer cardioprotection whereas EP 94 reduced myocardial infarct size in a dose-dependant manner. Protein expression of the κand δ-opioid receptors was detected in the left ventricle, with an up-regulation of the δ subtype after ischemia and reperfusion. The μ-opioid receptor was not detected. Conclusions: CsA did not reduce myocardial infarct size, whereas the novel enkephalin analogue EP 94 conferred cardioprotection in different porcine models. The κand δ-opioid receptors were detected in the pig left ventricle.