Division of Cardiology, Department of Medicine, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Division of Hematology and Oncology, McAllister Heart Institute, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Thromb Res. 2018 Jul;167:128-134. doi: 10.1016/j.thromres.2018.05.015. Epub 2018 May 17.
Rivaroxaban selectively inhibits factor Xa (FXa), which plays a central role in blood coagulation. In addition, FXa activates protease-activated receptor-2 (PAR-2). We have shown that PAR-2 mice exhibit less cardiac dysfunction after cardiac injury.
Wild-type (WT) and PAR-2 mice were subjected to left anterior descending artery (LAD) ligation to induce cardiac injury and heart failure. Mice received either placebo or rivaroxaban chow either starting at the time of surgery or 3 days after surgery and continued up to 28 days. Cardiac function was measured by echocardiography pre-surgery and 3, 7 and 28 days after LAD ligation. We also measured anticoagulation, intravascular thrombi, infarct size, cardiac hypertrophy and inflammation at various times.
Rivaroxaban increased the prothrombin time and inhibited the formation of intravascular thrombi in mice subjected to LAD ligation. WT mice receiving rivaroxaban immediately after surgery had similar infarct sizes at day 1 as controls but exhibited significantly less impairment of cardiac function at day 3 and beyond compared to the placebo group. Rivaroxaban also inhibited the expansion of the infarct at day 28. Rivaroxaban did not significantly affect the expression of inflammatory mediators or a neutrophil marker at day 2 after LAD ligation. Delaying the start of rivaroxaban administration until 3 days after surgery failed to preserve cardiac function. In addition, rivaroxaban did not reduce cardiac dysfunction in PAR-2 mice.
Early administration of rivaroxaban preserves cardiac function in mice after LAD ligation.
利伐沙班选择性抑制因子 Xa（FXa），FXa 在血液凝固中起着核心作用。此外，FXa 还能激活蛋白酶激活受体-2（PAR-2）。我们已经证明，PAR-2 小鼠在心脏损伤后表现出较少的心脏功能障碍。
野生型（WT）和 PAR-2 小鼠接受左前降支（LAD）结扎以诱导心脏损伤和心力衰竭。小鼠接受安慰剂或利伐沙班饲料，要么在手术时开始，要么在手术后 3 天开始，并持续至 28 天。在 LAD 结扎前、后 3、7 和 28 天通过超声心动图测量心脏功能。我们还在不同时间测量了抗凝、血管内血栓形成、梗死面积、心脏肥大和炎症。
利伐沙班增加了凝血酶原时间并抑制了 LAD 结扎小鼠血管内血栓的形成。手术后立即接受利伐沙班的 WT 小鼠在第 1 天的梗死面积与对照组相似，但与安慰剂组相比，在第 3 天及以后的心脏功能受损明显较小。利伐沙班还抑制了第 28 天的梗死扩张。利伐沙班在 LAD 结扎后第 2 天对炎症介质或中性粒细胞标志物的表达没有显著影响。延迟开始利伐沙班治疗直到手术后 3 天未能保留心脏功能。此外，利伐沙班并未减少 PAR-2 小鼠的心脏功能障碍。
在 LAD 结扎后早期给予利伐沙班可保留小鼠的心脏功能。
