Serial changes of soluble endothelin-1 levels during myocardial ischaemia-reperfusion. Effects of magnesium, diltiazem and a novel MAC-1 inhibitor.

The key role of endothelin-1 (ET-1) has been recognised in patients with ischaemic heart disease. However, the serial changes of ET-1 during both brief and prolonged ischaemia-reperfusion are poorly known. Serial changes of plasma ET-1 were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem and a MAC-1 inhibitor on the plasma ET-1 were elucidated. Forty-nine swine underwent brief (8 min) or prolonged (50 min) coronary artery occlusion followed by reperfusion. ET-1 plasma concentration was measured by ELISA at prespecified time points. The occlusion was associated with a decline of ET-1 followed by a significant increase during the reperfusion. Mg as well as diltiazem similarly affected the plasma ET-1 by reducing ET-1 release during the first hour of the reperfusion period. MAC-1 inhibition was also associated with decreases of ET-1. Ability of Mg, diltiazem and leumedins to decrease the ET-1 plasma level may have direct clinical implications for the use of these agents in patients with coronary artery disease.