Thrombosis |
From the Vascular Physiology and Thrombosis Research Laboratory of the Atherosclerosis Research Center, the Burns and Allen Research Institute, the Division of Cardiology and the Department of Medicine, Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, Calif, and the Chaim Sheba Medical Center (M.S.), Tel Hashomer, Israel.
Correspondence to Sanjay Kaul, MD, Division of Cardiology, Room 5314, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail kaul{at}cshs.org
Abstract We investigated the effects of magnesium on acute platelet-dependent stent thrombosis in an ex vivo porcine arteriovenous shunt model of high-shear blood flow. 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=156 perfusion runs in 10 swine). Animals were treated with intravenous heparin or MgSO4 alone (2 g bolus over 20 minutes, followed by 2 g/h infusion) and combined heparin plus MgSO4 in random fashion. Effects on thrombus weight (TW), platelet aggregation, bleeding time, activated clotting time, mean arterial blood pressure, and heart rate were quantified. Data points in the magnesium-treated animals were examined within 20 minutes after bolus (Mg-early) and >40 minutes after bolus (Mg-late). Stent TW (20±3 mg, pretreatment) was reduced by 42±21%, 47±19%, 48±16%, 67±12%, and 86±8% in the groups treated with Mg-early alone, Mg-late alone, heparin alone, heparin+Mg-early, and heparin+Mg-late, respectively (all P<0.001 versus pretreatment, P<0.001 for heparin+Mg-early and Mg-late versus heparin or magnesium alone, and P<0.05 for heparin+Mg-late versus heparin+Mg-early, ANOVA). Magnesium had no significant effect on platelet aggregation, activated clotting time, or bleeding time. There were no significant effects on heart rate or mean arterial blood pressure. The serum magnesium level was inversely correlated with TW (r=-0.70, P=0.002). In conclusion, treatment with intravenous MgSO4 produced a time-dependent inhibition of acute stent thrombosis under high-shear flow conditions without any hemostatic or significant hemodynamic complications. Thus, magnesium may be an effective agent for preventing stent thrombosis.
Key Words: platelets antithrombotic effects animal models experimental thrombosis
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