Monoclonal antibody against the platelet glycoprotein (GP) IIb/IIIa receptor prevents coronary artery reocclusion after reperfusion with recombinant tissue-type plasminogen activator in dogs.
Localized thrombosis was produced in the left anterior descending (LAD) coronary artery of open chest dogs by constricting a segment so as to produce greater than 90% stenosis (reducing blood flow to 40 +/- 10% of baseline), and placing a thrombus in the segment immediately proximal to the stenosis by inducing endothelial cell injury and instilling a mixture of blood and thrombin. Intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) at a rate of 15-30 micrograms/kg per min for 30 or 60 min in eight dogs induced coronary artery reperfusion within 23 +/- 7 min (mean +/- SD), but reocclusion occurred despite heparin anticoagulation in all but one of these dogs within 7 +/- 5 min. Intravenous injection of 0.8 mg/kg of the F(ab')2 fragment of a monoclonal antibody (7E3) directed against the platelet GPIIb/IIIa receptor, prevented reocclusion in 10/10 dogs during an observation period of 2 h (P less than 0.001 vs. rt-PA alone). The antibody abolished ADP-induced platelet aggregation and markedly prolonged the bleeding time. Intravenous aspirin or dipyridamole prevented reocclusion for 1 h or more in only 2/7 and 1/6 dogs, respectively. We conclude that the monoclonal antibody is very effective in preventing reocclusion after successful thrombolysis of occluded coronary arteries with rt-PA.
Yasuda
T
T
Cardiac Division, Massachusetts General Hospital, Boston 02114.
Gold
H K
HK
Fallon
J T
JT
Leinbach
R C
RC
Guerrero
J L
JL
Scudder
L E
LE
Kanke
M
M
Shealy
D
D
Ross
M J
MJ
Collen
D
D
Coller
B S
BS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D003327:Coronary Disease / Q000628:therapy*; D003328:Coronary Thrombosis / Q000473:pathology / Q000628:therapy*; D004176:Dipyridamole / Q000627:therapeutic use; D004285:Dogs; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D008855:Microscopy, Electron, Scanning; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D004176:Dipyridamole; D010959:Tissue Plasminogen Activator; D001241:Aspirin