Antagonism of the platelet 5HT2 receptor in the presence of thrombolysis.
Thrombolysis of coronary arterial thrombi is often accompanied by occlusion due to continued platelet thrombosis. We modified the Folts' model of intracoronary thrombosis (critical stenosis with endothelial damage) to produce up to 35-min occlusions of the circumflex coronary artery in seven open-chest anaesthetised dogs. Administration of recombinant plasminogen activator (rtPA 200 micrograms.kg-1 bolus plus 1 mg.kg-1.h-1 infusion), without heparin or aspirin, always produced effective thrombolysis. Fibrinogen decreased (P < 0.05), thrombin time increased (P < 0.025), bleeding time trebled (P < 0.025) and initial arterial patency was achieved. Addition of a selective 5HT2 antagonist, increased coronary blood flow (P < 0.01) and reduced rethrombosis rate (P < 0.025), but did not affect coagulation or bleeding. The time the vessel spent occluded was significantly decreased (P < 0.01) and correlated with the fibrinogen level (r = 0.97, P < 0.01), thereby implying the presence of fibrin within the thrombus. After rt-PA was withdrawn, bleeding time and fibrinogen level normalised within 30 and 60 min, respectively, but full coronary patency was maintained. Thus, when rt-PA alone had produced full thrombolysis, 5HT2 antagonism prevented intracoronary thrombosis without additional bleeding complications.
Belcher
P R
PR
Academic Medicine, Charing Cross & Westminster Medical School, London, UK.
Drake-Holland
A J
AJ
Noble
M I
MI
D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D003328:Coronary Thrombosis / Q000517:prevention & control; D004285:Dogs; D005340:Fibrinogen / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D015912:Thrombolytic Therapy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D011994:Recombinant Proteins; D012702:Serotonin Antagonists; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator