Myocardial reperfusion after prolonged periods of ischemia may result in the acceleration and exacerbation of ventricular injury. This is associated with intramitochondrial calcium overload and gross alterations in ultrastructure. Prostaglandins (PGs) (e.g., PGE2, PGE2 alpha, thromboxane A2, PGl2) are synthesized by the heart during myocardial infarction, and cardiotoxic influences of arachidonate on contractile recovery with enhanced efflux of enzymes occur after reperfusion. Accumulation of arachidonic acid in early ischemia indicates degradation of phospholipids as structural components of myocyte membranes. One major cause for reperfusion-induced exacerbation of ischemic damage is a free radical-induced peroxidation of lipids with cellular disruption. On reperfusion, both vasoconstrictive and dilator PGs are released from platelets, myocytes, and endothelium, and flushed downstream. This may cause additional vasoconstriction in the microcirculation of normally and/or hypoperfused cardiac regions. Locally released vasodilating PGs can improve cardiac perfusion and prevent plugging of blood elements, thereby antagonizing cell destruction during flow restoration. Several drugs are available that modify blood cell and myocyte arachidonate metabolism, and may favor synthesis of dilating and antiaggregatory PGs.