TY - JOUR T1 - Targeted Antioxidant Properties of<em>N</em>-[(Tetramethyl-3-pyrroline-3-carboxamido)propyl]phthalimide and Its Nitroxide Metabolite in Preventing Postischemic Myocardial Injury JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 838 LP - 845 VL - 292 IS - 3 AU - Ravi A. Shankar AU - Kalman Hideg AU - Jay L. Zweier AU - Periannan Kuppusamy Y1 - 2000/03/01 UR - http://jpet.aspetjournals.org/content/292/3/838.abstract N2 - We investigated the cardioprotective efficacy of a new compound based on 2,2,5,5-tetramethyl-3-pyrroline-3-carboxamide (TPC-NH). Biochemical studies using electron paramagnetic resonance (EPR) spectroscopy suggest thatTPC-NH is a scavenger of reactive oxygen species. In vitro cellular studies show that TPC-NH protects isolated cardiomyocytes against oxidative damage caused by superoxide radicals. Ex vivo EPR studies on the isolated rat heart indicate that the TPC-NH is metabolically oxidized to the nitroxide form. Studies were also performed in the isolated rat heart model to measure the efficacy of TPC-NH and its metabolites in preventing postischemic reperfusion injury. Serial measurements of contractile function were performed on hearts subjected to ischemia-reperfusion. Hearts were either untreated or treated with 50 μM TPC-NH or with its metabolites for 1 min before ischemia and during the first 5 min of reflow. TPC-NH showed marked protection with a more than 3-fold increased recovery of contractile function compared with control hearts, whereas its oxidative metabolites exhibited significant but lower protection. Thus,TPC-NH and, to a lesser extent, its oxidation metabolites exhibit potent membrane-targeted antioxidant action and exert marked protection against myocardial injury in the postischemic heart. The American Society for Pharmacology and Experimental Therapeutics ER -