Heart Rate Reduction with Ivabradine Prevents Cardiac Rupture after Myocardial Infarction in Mice
Heart Rate Reduction with Ivabradine Prevents Cardiac Rupture after Myocardial Infarction in Mice
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DOI：
10.1007/s10557-020-07123-5
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发表时间：
2021-01-07
影响因子：
3.4
通讯作者：
Tsutsui, Hiroyuki
中科院分区：
文献类型：
--
作者：
Ikeda, Masataka;Ide, Tomomi;Tsutsui, Hiroyuki
目的 心脏破裂是心肌梗死 (MI) 后的致命并发症。据报道，心率（HR）增加是急性心肌梗死期间心脏破裂的独立危险因素。然而，HR 降低在 MI 后心脏破裂中的作用仍有待充分阐明。我们的目的是评估伊伐布雷定（IVA）降低心率对心肌梗死后小鼠心脏破裂的治疗效果。方法通过结扎左冠状动脉前降支诱导小鼠心肌梗死。随后，我们在术后 24 小时将充满 IVA 溶液或载体 (Veh) 的渗透泵植入存活的 MI 小鼠皮下。我们在第 5 天对心肌进行生化分析，另外观察小鼠 10 天，并分析心脏破裂和非心脏破裂死亡率以及 MI 后的生存率。结果 IVA 治疗组小鼠的 HR 显着降低，而两组之间的血压相当。与 Veh 治疗的小鼠相比，IVA 治疗的小鼠 MI 边缘区的细胞凋亡显着减少。尽管两组存活的 MI 小鼠的梗死面积没有差异，但 IVA 降低 HR 显着减少了心脏破裂（Veh 治疗组和 IVA 治疗组的破裂率分别为 26% 和 8%），并改善了 MI 后的存活率。 结论 我们的研究结果表明，IVA 降低 HR 可以预防 MI 后的心脏破裂。这对于心率较高的 MI 患者尤其有效，这些患者要么无法充分耐受 β 受体阻滞剂，要么尽管接受了 β 受体阻滞剂，但 HR 仍然很高。
Purpose Cardiac rupture is a fatal complication following myocardial infarction (MI). An increase in heart rate (HR) is reportedly an independent risk factor for cardiac rupture during acute MI. However, the role of HR reduction in cardiac rupture after MI remains to be fully elucidated. We aimed to evaluate the therapeutic efficacy of HR reduction with ivabradine (IVA) on post-MI cardiac rupture in mice.Methods We induced MI in mice by ligating the left anterior descending coronary artery. Subsequently, we subcutaneously implanted osmotic pumps filled with IVA solution or vehicle (Veh) in the surviving MI mice at 24 h postoperatively. We biochemically analyzed the myocardium on day 5, additionally observed the mice for 10 days, and analyzed the rates of cardiac rupture and non-cardiac rupture death, and survival after MI.Results HR was significantly lower in the IVA-treated mice, whereas blood pressure was comparable between the two groups. Compared to the Veh-treated mice, apoptosis was significantly reduced in the MI border zone in the IVA-treated mice. Although there were no differences in the infarct size of the surviving MI mice between the two groups, HR reduction with IVA significantly reduced cardiac rupture (rupture rate 26 and 8% in the Veh-treated and IVA-treated groups, respectively) and improved survival after MI.Conclusion Our findings suggest that HR reduction with IVA prevents cardiac rupture after MI. This may be particularly effective in MI patients with a high HR who are either unable to adequately tolerate beta-blockers or whose HR remains high despite receiving beta-blockers.