Pauley Heart Center, Department of Internal Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Virginia; Department of Cardiology, Clinic Hospital, School of Medicine, Republic University, Montevideo, Uruguay.
Pauley Heart Center, Department of Internal Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Virginia.
J Am Coll Cardiol. 2018 Nov 6;72(19):2342-2356. doi: 10.1016/j.jacc.2018.07.102.
Sacubitril/valsartan (SAC/VAL) is approved by the U.S. Food and Drug Administration for heart failure with reduced ejection fraction (HFrEF).
This study investigated the effects of SAC/VAL on acute myocardial infarction (MI) and cardiac remodeling in a translational rabbit model of MI.
New Zealand White rabbits were sedated and underwent conscious MI (45-min ischemia) by balloon inflation (previously implanted surgically) followed by 72 h (acute protocol) or 10 weeks (chronic protocols) of reperfusion. "Infarct-sparing" protocol: SAC/VAL, VAL, or placebo were randomly allocated and administered at reperfusion. "HFrEF-treatment" protocol: rabbits were randomized, and treatment commenced after echocardiography-confirmed left ventricular ejection fraction (LVEF) ≤40%. "HFrEF-prevention" protocol: treatment started at reperfusion and continued daily throughout the study.
Compared with placebo, SAC/VAL and VAL significantly reduced infarct size (TTC staining) and plasma troponin levels; however, only SAC/VAL preserved LVEF at 72 h post-MI. In the HFrEF-treatment protocol, LVEF improvement was observed with SAC/VAL compared with both placebo and VAL starting 2 weeks post-treatment, a benefit that persisted throughout study duration. In the HFrEF-prevention protocol, SAC/VAL and VAL attenuated the decline in LVEF post-MI, although SAC/VAL offered better functional protection. The functional improvement observed in both treatment protocols was paralleled by significant reduction in left ventricular (LV) scar size (Picrosirius red staining) in the SAC/VAL groups.
Reperfusion therapy with SAC/VAL or VAL offers robust acute infarct-sparing benefits; however, SAC/VAL treatment offered superior short-term and long-term benefits in preventing MI-induced LV dysfunction compared with VAL. SAC/VAL also significantly attenuated LV scar size following MI compared with placebo, whereas VAL did not reach statistical significance in scar reduction.
沙库巴曲缬沙坦（SAC/VAL）已被美国食品和药物管理局批准用于射血分数降低的心力衰竭（HFrEF）。
本研究旨在通过兔心肌梗死模型，探讨 SAC/VAL 对急性心肌梗死（MI）及心脏重构的影响。
新西兰白兔镇静后通过球囊膨胀（术前植入）行 MI（45 分钟缺血），随后进行 72 小时（急性组）或 10 周（慢性组）的再灌注。“梗死保护”方案：在再灌注时随机给予 SAC/VAL、VAL 或安慰剂。“HFrEF 治疗”方案：兔随机分组，在超声心动图证实左心室射血分数（LVEF）≤40%后开始治疗。“HFrEF 预防”方案：在再灌注时开始治疗，整个研究期间每日用药。
与安慰剂相比，SAC/VAL 和 VAL 显著减少梗死面积（TTC 染色）和血浆肌钙蛋白水平，但只有 SAC/VAL 在 MI 后 72 小时时保留了 LVEF。在 HFrEF 治疗方案中，与安慰剂和 VAL 相比，SAC/VAL 治疗 2 周后开始改善 LVEF，且该获益持续至研究结束。在 HFrEF 预防方案中，SAC/VAL 和 VAL 减轻了 MI 后 LVEF 的下降，但 SAC/VAL 提供了更好的功能保护。两种治疗方案中观察到的功能改善与 SAC/VAL 组左心室（LV）瘢痕面积（苦味酸天狼星红染色）的显著减少相平行。
再灌注治疗 SAC/VAL 或 VAL 可提供强大的急性梗死保护作用；然而，与 VAL 相比，SAC/VAL 治疗在预防 MI 诱导的 LV 功能障碍方面具有更好的短期和长期获益。与安慰剂相比，SAC/VAL 还显著减轻了 MI 后的 LV 瘢痕面积，而 VAL 在减少瘢痕方面未达到统计学意义。
