Comparative antithrombotic effects of magnesium sulfate and the platelet glycoprotein IIb/IIIa inhibitors tirofiban and eptifibatide in a canine model of stent thrombosis.
BACKGROUND
Antithrombotic effects of glycoprotein IIb/IIIa inhibitors and magnesium are known, but their comparative effects on stent thrombosis are not known. Our objective was to compare the antithrombotic effects of the glycoprotein IIb/IIIa inhibitors tirofiban and eptifibatide with magnesium in an ex vivo canine arteriovenous shunt model of stent thrombosis.


RESULTS
Control nitinol stents were expanded to 2 mm in diameter in a tubular perfusion chamber interposed in the shunt and exposed to flowing arterial blood at a shear rate of 2100 s(-1) for 20 minutes (n=398 perfusion runs in 24 experiments in 8 dogs). The animals were treated intravenously with MgSO4 (2 g bolus x 20 minutes followed by 2 g/h infusion), eptifibatide (double bolus of 180 microg/kg 10 minutes apart followed by 2 microg/kg per minute), or tirofiban (0.3 microg/kg per minute), with or without heparin (50 U/kg). Effects of the test agents on thrombus weight, platelet aggregation (PA), platelet CD62 expression, bleeding time (BT), heart rate, and mean arterial blood pressure were assessed. Treatment with Mg+heparin reduced stent thrombus weight by 78+/-10% compared with baseline (19+/-4 mg, P<0.001). The antithrombotic effect of Mg+heparin was equivalent to that observed with tirofiban+heparin (78+/-13%) and eptifibatide+heparin (84+/-11%). Magnesium had no significant effect on PA and BT. Tirofiban and eptifibatide inhibited PA by >90% and prolonged BT up to 20 minutes. None of the test agents had effects on CD62 expression or activated clotting time. There were no significant bleeding or hemodynamic complications.


CONCLUSIONS
Magnesium produced a significant reduction in acute stent thrombus formation that was equivalent in magnitude to that produced by clinically relevant doses of tirofiban and eptifibatide. Its potential use in percutaneous coronary intervention requires further study.
Rukshin
Vladimir
V
Vascular Physiology and Thrombosis Research Laboratory of the Atherosclerosis Research Center, Cedars-Sinai Burns and Allen Research Institute, Los Angeles, Calif, USA.
Shah
Prediman K
PK
Cercek
Bojan
B
Finkelstein
Ariel
A
Tsang
Vivian
V
Kaul
Sanjay
S
D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D000077542:Eptifibatide; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D008278:Magnesium Sulfate / Q000097:blood / Q000627:therapeutic use*; D019007:P-Selectin / Q000032:analysis; D010455:Peptides / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D015607:Stents / Q000009:adverse effects; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D019007:P-Selectin; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D008278:Magnesium Sulfate; D006493:Heparin; D000077466:Tirofiban; D000077542:Eptifibatide