The lazaroid U74006F, a 21-aminosteroid inhibitor of lipid peroxidation, attenuates myocardial injury from ischemia and reperfusion.
U74006F, a novel new 21-aminosteroid inhibitor of lipid peroxidation, has been effective in preventing free-radical-mediated injury in central nervous system models. To assess its ability to diminish myocardial injury due to ischemia and reperfusion, U74006F (n = 11) or its vehicle (n = 11) were administered intravenously to New Zealand white rabbits. After allowing for distribution, the hearts were excised and exposed to 30 min of stop-flow ischemia and 30 min of reperfusion on a nonrecirculating Langendorf apparatus. There was diminished creatine phosphokinase release; improved peak positive dP/dt, developed pressure, and peak negative dP/dt; and diminished diastolic pressure in the group treated with U74006F. Thus, pretreatment with U74006F diminished myocardial injury and enhanced systolic and diastolic functional recovery, probably by protecting the lipid component of cell membranes from peroxidation by reactive oxygen metabolites.
Carrea
F P
FP
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
Lesnefsky
E J
EJ
Kaiser
D G
DG
Horwitz
L D
LD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D003402:Creatine Kinase / Q000097:blood; D005609:Free Radicals; D006439:Hemodynamics / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D011281:Pregnatrienes / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D016277:Ventricular Function, Left / Q000187:drug effects
D005609:Free Radicals; D008054:Lipid Peroxides; D011281:Pregnatrienes; D003402:Creatine Kinase; C053355:tirilazad