Prevention of lipid peroxidation does not prevent oxidant-induced myocardial contractile dysfunction.
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 non-recirculating Langendorff technique. Six U74006F- and six V-treated hearts were exposed for 7.5 min to a .OH-generating system (H2O2 and Fe(2+)-ADP chelate). Myocardial lipid peroxides were measured by glutathione peroxidase-catalyzed oxidation of exogenous glutathione. With exposure to .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 .OH. Therefore, factors other than lipid peroxidation play a major role in oxidant-induced myocardial stunning.
Kong
Y
Y
Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262.
Lesnefsky
E J
EJ
Ye
J
J
Horwitz
L D
LD
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology / Q000517:prevention & control*; D003326:Coronary Circulation / Q000187:drug effects; D003971:Diastole; D005260:Female; D005296:Ferrous Compounds / Q000494:pharmacology; D005609:Free Radicals; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress; D011281:Pregnatrienes / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D013599:Systole
D005296:Ferrous Compounds; D005609:Free Radicals; D008054:Lipid Peroxides; D011281:Pregnatrienes; D000244:Adenosine Diphosphate; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; C053355:tirilazad