Prevention of lipid peroxidation does not prevent oxidant-induced myocardial contractile dysfunction
Kong, Y.; Lesnefsky, E.J.; Ye, J.; Horwitz, L.D.
American Journal of Physiology 267(6 Pt 2): H2371-H2377
1994
ISSN/ISBN: 0002-9513 PMID: 7810737 Document Number: 436758
We tested whether, with exposure to an extraneous iron-catalyzed free radical-generating system, prevention of lipid peroxidation with U74006F, a 21-aminosteroid, could also prevent myocardial contractile dysfunction. Rabbits received either U74006F (10 mg/kg iv) or vehicle (V). Thirty minutes later the hearts were excised and perfused by a nonrecirculating Langendorff technique. Six U74006F- and six V-treated hearts were exposed for 7.5 min to a cntdot OH-generating system (H-2O-2 and Fe-2+-ADP chelate). Myocardial lipid peroxides were measured by glutathione peroxidase-catalyzed oxidation of exogenous glutathione. With exposure to cntdot OH, cytosolic lipid peroxide levels were increased threefold in V-treated hearts, but there was no increase in U74006F-treated hearts. After 30 min of recovery, developed pressure and maximum first derivative of left ventricular pressure were greater in U74006F-treated hearts than in V-treated hearts but were still 50 and 44% of levels in saline hearts, respectively. Coronary flow was markedly reduced after exposure to free radicals and was only slightly less depressed when U74006F was administered. When coronary flow following oxidant exposure was increased by nitroglycerin, U74006F again only modestly improved systolic function. Thus, although U74006F blocked lipid peroxidation, it only slightly improved the ventricular dysfunction caused by cntdot OH. Therefore, factors other than lipid peroxidation play a major role in oxidant-induced myocardial stunning.