The endothelin system and its role in acute myocardial infarction

Endothelin (ET)-1 is a potent coronary vasoconstrictor. On the heart, ET-1 is a potent positive inotrope and may be pro-arrhythmic. Plasma ET-1 levels are raised after acute myocardial infarction (AMI) and recanilisation in humans. This probably contributes to the coronary vasoconstriction that underlies the myocardial ischaemia and ventricular dysfunction at this time. During occlusion of the rat coronary artery, ventricular arrhythmias are reduced by ETA receptor blockade. Short-term ETA receptor blockade also reduces infarct size in animal models of AMI (coronary occlusion followed by reperfusion). Blockade of the endothelin-converting enzyme with SM-19712 reduced the infarct size in the rabbit model of AMI. ETA receptor blockade is associated with coronary artery dilation in humans. As there are indications that ETA receptor antagonists are protective in animal models of AMI, short-term ETA receptor blockade should be considered for trial in human AMI.