Heart Rate Reduction with Ivabradine Prevents Cardiac Rupture after Myocardial Infarction in Mice

• Published in: Cardiovascular drugs and therapy 2022-04, Vol.36 (2), p.257-262
• Main Authors: Ikeda, Masataka, Ide, Tomomi, Furusawa, Shun, Ishimaru, Kosei, Tadokoro, Tomonori, Miyamoto, Hiroko Deguchi, Ikeda, Soichiro, Okabe, Kosuke, Ishikita, Akihito, Abe, Ko, Matsushima, Shouji, Tsutsui, Hiroyuki
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Blood pressure; Cardiology; Coronary artery; Heart attacks; Heart Rate; Heart Rupture - complications; Heart Rupture - drug therapy; Humans; Ivabradine - pharmacology; Ivabradine - therapeutic use; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Myocardial infarction; Myocardial Infarction - drug therapy; Myocardium; Risk analysis; Risk factors; Rupture; Short Communication; Survival; Ventricular Remodeling
• ISSN: 0920-3206; 1573-7241
• DOI: 10.1007/s10557-020-07123-5

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 β-blockers or whose HR remains high despite receiving β-blockers.