Serial changes of the plasma prostanoids during myocardial ischemia-reperfusion in swine. Effects of magnesium, diltiazem, and a novel Mac-1 inhibitor

The key role of prostanoids has been recognized in patients with ischemic heart disease. However, serial changes of thromboxane and prostacyclin during both brief and prolonged ischemia-reperfusion are poorly known. These plasma prostanoids were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on the level of the stable metabolites of thromboxane (TXB₂) and prostacyclin (6-keto-PGF(1α)) were elucidated. Forty-nine swine underwent brief (8 min) or prolonged (50 min) coronary artery occlusion followed by reperfusion. The occlusion phase was associated with a decline of plasma prostanoids, followed by a significant increase during reperfusion. Mg and diltiazem similarly affected plasma prostanoids by reducing TXB₂ release at 1 h of reperfusion. There was, however, no effect on plasma 6-keto-PGF(1α). The Mac-1 inhibition was associated with stabilization of both antagonistic prostanoids as well. Ability of Mg, diltiazem, and leumedins to favorably modulate plasma prostanoid levels have direct clinical implications for the use of these agents in patients with coronary artery disease.