Use of aromatic hydroxylation of phenylalanine to measure production of hydroxyl radicals after myocardial ischemia in vivo. Direct evidence for a pathogenetic role of the hydroxyl radical in myocardial stunning.

A pathogenetic role of .OH in myocardial stunning has been inferred from the protective effects of .OH scavengers and iron chelators. However, conclusive demonstration of the .OH radical hypothesis of myocardial stunning requires direct verification of three major, but still unproven, assumptions: (1) .OH is produced in the stunned myocardium in vivo; (2) antioxidant therapy inhibits .OH production; and (3) such inhibition results in enhanced recovery of contractility (ie, .OH is necessary for the development of myocardial stunning). Since phenylalanine (Phe) reacts with .OH to form the hydroxylated products ortho-, meta-, and para-tyrosines (o-, m-, and p-tyr), we used aromatic hydroxylation of Phe to detect .OH formation in the stunned myocardium. Open-chest dogs undergoing a 15-minute coronary occlusion followed by reperfusion received an intravenous infusion of Phe (54.3 mg/kg for 11.5 minutes beginning 90 seconds before reperfusion); these animals were given either no antioxidant therapy (group I, n ...