Short-term intravenous eptifibatide infusion combined with reduced dose recombinant tissue plasminogen activator inhibits platelet recruitment at sites of coronary artery injury.
OBJECTIVE
This study was designed to determine in a dog model of coronary thrombosis whether short-term eptifibatide (Ep) combined with low-dose plasminogen activator (rt-PA) inhibits platelet recruitment at sites of endothelial damage after normalization of platelet function.


BACKGROUND
Ep plus reduced-dose rt-PA has not previously been shown to render a recanalized coronary artery resistant to platelet recruitment after normalization of platelet function.


METHODS
Inhibition of platelet recruitment was studied by scanning electron microscopy (SEM) in a canine model of left anterior descending (LAD) thrombosis. In phase I treatment groups were: 1) Ep (n = 6); 2) Ep + rt-PA (n = 6); 3) rt-PA (n = 6); and 4) placebo (n = 4). Coronary blood flow was monitored and LAD segments excised for SEM after 90-min infusion of study drug. In phase II, dogs were randomized to Ep alone (n = 5) or to Ep + rt-PA (n = 5). Coronary blood flow was monitored during and 120 min after cessation of drug when platelet function had returned to normal and LAD segments were excised.


RESULTS
All animals except placebo showed reflow. In phase I, SEM showed an absence of platelet aggregates with Ep alone and with Ep + rt-PA, but not with rt-PA alone. In phase II, SEM showed an intimal surface devoid of mural thrombus and platelet aggregates only in Ep + rt-PA treated arteries. Ep-alone treated arteries showed new platelet aggregates at sites of residual mural thrombus.


CONCLUSIONS
Short-term infusion Ep plus low-dose rt-PA acutely neutralizes the ability of damaged endothelial surfaces to recruit new platelets by inhibiting platelet aggregation and eliminating residual mural thrombus.
Rubenstein
Mark H
MH
Cardiac Unit and the Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Finn
Aloke V
AV
Leinbach
Robert C
RC
Hollenbach
Stanley
S
Aretz
H Thomas
HT
Virmani
Renu
R
Gold
Herman K
HK
D000818:Animals; D003324:Coronary Artery Disease / Q000188:drug therapy*; D003326:Coronary Circulation / Q000187:drug effects*; D003328:Coronary Thrombosis / Q000188:drug therapy; D004285:Dogs; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects*; D000077542:Eptifibatide; D007262:Infusions, Intravenous; D023421:Models, Animal; D010455:Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D010960:Plasminogen Activators / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D000077542:Eptifibatide