La inhibición específica del factor Xa reduce la reestenosis tras la angioplastia con balón de arterias femorales ateroscleróticas en conejos

BACKGROUND: Balloon angioplasty of atherosclerotic arteries results in activation of the coagulation cascade. Several coagulation factors, including factor Xa and thrombin, are mitogenic for vascular smooth muscle cells in vitro and thus may play a role in restenosis after balloon angioplasty. Specific inhibition of factor Xa can be achieved with recombinant antistasin (rATS) or tick anticoagulant peptide (rTAP). We hypothesized that inhibition of Xa would limit restenosis after balloon angioplasty in an atherosclerotic rabbit model. METHODS AND RESULTS: Focal femoral atherosclerosis was induced by air desiccation injury and a high-cholesterol diet in 38 New Zealand White rabbits. Recombinant antistasin (n = 20 arteries) or rTAP (n = 14 arteries) was administered by intravenous bolus at the time of balloon angioplasty and followed by a 2-hour infusion; controls (n = 21 arteries) received bolus heparin alone (150 U/kg). Therapeutic prolongation of the activated partial thromboplastin time occurred, and antithrombotic drug levels were achieved in all animals. Luminal diameter in millimeters by quantitative angiography did not differ between treatment groups before (1.1 +/- 0.2 for controls, 1.1 +/- 0.2 for rATS, and 1.1 +/- 0.3 for rTAP) or after balloon angioplasty (1.5 +/- 0.3 for controls, 1.4 +/- 0.2 for rATS, and 1.4 +/- 0.2 for rTAP). At 28 days, treatment with factor Xa inhibitors tended to result in arteries with larger luminal diameter than controls (1.2 +/- 0.3 for rATS, 1.2 +/- 0.3 for rTAP versus 1.0 +/- 0.3 for control, P = .09 by one-way ANOVA). Restenosis, defined as reduction in angiographic luminal diameter (in mm) from 2 hours after angioplasty to 28 days after angioplasty was less in the rATS group than in controls (-0.2 +/- 0.1 versus -0.5 +/- 0.4, P < .001) and tended to be less in the rTAP group (-0.3 +/- 0.2 versus -0.5 +/- 0.4, P = .07). Quantitative histopathological analysis showed less percent cross-sectional area narrowing by plaque in both rATS- and rTAP-treated arteries compared with controls (42 +/- 21%, 47 +/- 18%, and 63 +/- 14%, respectively; P < .01 by one-way ANOVA). CONCLUSIONS: We conclude that a 2-hour infusion of rATS or rTAP reduced angiographic restenosis and resulted in less luminal cross-sectional narrowing by plaque compared with controls.

Resumen tomado de PubMed (NCBI) para el registro citado, en el idioma original. La versión de referencia es la de la publicación original.

El resumen se deja sin traducir para conservar la redacción original de los autores.

En 38 conejos ateroscleróticos se compararon rATS (n = 20 arterias) y rTAP (n = 14) frente a heparina (n = 21) tras angioplastia con balón. A los 28 días, la reestenosis con rATS fue de -0,2 ± 0,1 mm frente a -0,5 ± 0,4 mm con heparina (P < 0,001). El estrechamiento por placa fue del 42 ± 21 % (rATS), 47 ± 18 % (rTAP) y 63 ± 14 % (heparina) (P < 0,01). Los autores concluyen que una infusión de 2 horas de rATS o rTAP redujo la reestenosis.

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