Effects of lodoxamide on ischemic reperfused myocardium.
The beneficial effects of lodoxamide tromethamine (U42585E) have been examined in a canine model of myocardial ischemic injury. Lodoxamide was infused 20 mg/kg/h i.v. starting 30 min before occlusion of the proximal left circumflex coronary artery (LCX) and continuing through 90 min of ischemia. Lodoxamide produced a significant reduction in ultimate infarct size measured at 24 h by postmortem tetrazolium perfusion staining. Infarct size expressed as a percent of the anatomical area at risk was 21.7 +/- 2.7 in the treated group vs. 47.0 +/- 3.1 in the control group (mean +/- SEM). No significant difference in area at risk was observed between treated and control groups. Salvage occurred primarily in subepicardial and midmyocardial tissue without apparent lateral protection. Histological examination confirmed gross results of postmortem staining. The protection appeared to be unrelated to myocardial oxygen demand since no hemodynamic differences between groups were observed at the time of occlusion of throughout the 24-h experimental course. Concurrent studies of ex vivo platelet aggregation showed no effect of lodoxamide on adenosine diphosphate (ADP), collagen, and arachidonic acid-induced aggregation. In vivo antithrombotic effects were evaluated in four conscious dogs by inducing LCX thrombosis with low-amperage stimulation (50 microA for 24 h) of the intimal surface. Occlusive thrombi occurred in all four dogs and were similar to controls. These results suggest that lodoxamide reduces myocardial ischemic injury by a mechanism unrelated to oxygen demand or antiplatelet effects.
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D009570:Nitriles; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D010477:Perfusion; D010979:Platelet Function Tests; D014325:Tromethamine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000596:Amino Acids; D009570:Nitriles; D014325:Tromethamine; C022028:lodoxamide tromethamine; D010072:Oxamic Acid