Leukotriene-receptor antagonist FPL-55712 and t-PA-induced thrombolysis in canine coronary thrombosis.

Abstract

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.

• Authors: J L Mehta, W W Nichols
• Journal: Thrombosis research (Thromb Res) Vol. 58 Issue 1 Pg. 13-21 (Apr 01 1990) ISSN: 0049-3848 [Print] United States
• PMID: 2160745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Chromones
• Leukotrienes
• SRS-A
• Superoxides
• FPL 55712
• Tissue Plasminogen Activator

Topics

• Animals
• Chromones (therapeutic use)
• Coronary Disease (drug therapy)
• Coronary Thrombosis (drug therapy)
• Dogs
• Drug Synergism
• Leukotrienes (physiology)
• Neutrophils (drug effects)
• Recurrence
• SRS-A (antagonists & inhibitors)
• Superoxides (metabolism)
• Thrombolytic Therapy (methods)
• Tissue Plasminogen Activator (therapeutic use)