Leukotriene-receptor antagonist FPL-55712 and t-PA-induced thrombolysis in canine coronary thrombosis.
Leukocyte-derived arachidonate products peptido-leukotrienes have been shown to induce coronary constriction and platelet aggregation. As such, leukocytes may have a role in coronary thrombosis and coronary re-occlusion following thrombolysis. In the present study, we examined the effects of tissue-plasminogen activator (t-PA, 0.75 mg/kg over 20 minutes) given after either saline or FPL-55712 (2 mg/kg), a peptido-leukotriene receptor antagonist, in dogs with electrically-induced coronary thrombosis. Peripheral blood neutrophil number and superoxide anion generation increased (P less than 0.01) during formation of thrombus and subsequent t-PA administration in saline-treated dogs. FPL-55712 pretreatment attenuated (P less than 0.05) the increase in number of and superoxide anion generation by neutrophils. However, frequency of thrombolysis, duration of restored flow and re-occlusion rates were similar (P-NS) in both groups of dogs. This study shows that FPL-55712 does not modulate the thrombolytic potential of t-PA even though it decreases neutrophil activation in response to myocardial ischemia.
Mehta
J L
JL
Division of Cardiology, University of Florida College of Medicine, Gainsville 326.
Nichols
W W
WW
D000818:Animals; D002867:Chromones / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy*; D003328:Coronary Thrombosis / Q000188:drug therapy*; D004285:Dogs; D004357:Drug Synergism; D015289:Leukotrienes / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects; D012008:Recurrence; D013189:SRS-A / Q000037:antagonists & inhibitors*; D013481:Superoxides / Q000378:metabolism; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D002867:Chromones; D015289:Leukotrienes; D013189:SRS-A; D013481:Superoxides; C006312:FPL 55712; D010959:Tissue Plasminogen Activator