Division of Pediatric Cardiology, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Department of Cardiac Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Int J Cardiol. 2022 Dec 1;368:62-68. doi: 10.1016/j.ijcard.2022.08.030. Epub 2022 Aug 18.
Nicorandil, an adenosine triphosphate-sensitive potassium channel agonist and nitric oxide donor, is a coronary vasodilator used to treat ischemia-induced chest pain, but it's potential cardioprotective benefits during open heart surgery have not been thoroughly investigated. The study objective was to assess the impact of nicorandil on postoperative ventricular dysfunction and end-organ injury in an established experimental model of open-heart surgery with cardiopulmonary bypass (CPB) and cardioplegic arrest. We hypothesized that nicorandil would attenuate myocardial ischemia-reperfusion (IR) injury, preserve ventricular function, and reduce end-organ injury.
Rabbits were cannulated for CPB, followed by 60 min of aortic cross-clamp (ACC) with cold cardioplegic arrest, and 120 min of recovery after ACC removal. Nicorandil (or normal saline vehicle) was given intravenously 5 min before ACC and continued throughout the recovery period. Left ventricular developed pressure (LVDP), systolic contractility (LV + dP/dt), and diastolic relaxation (LV -dP/dt) were continuously recorded, and blood and tissue samples were collected for measurement of oxidant stress (OS), inflammation, apoptosis, and organ injury.
Nicorandil significantly attenuated IR-induced LV dysfunction compared to saline control (R-120: LV + dP/dt: 1596 ± 397 vs. 514 ± 269 mmHg/s, p = 0.010; LV -dP/dt: -1524 ± 432 vs. -432 ± 243 mmHg/s, p < 0.001; LVDP: 55 ± 11 vs. 22 ± 5 mmHg, p = 0.046). Furthermore, nicorandil inhibited IR-induced increases in OS, inflammation, apoptosis, and organ injury.
Nicorandil exhibits myocardial protection by attenuation of IR-induced LV dysfunction associated with OS, inflammation, apoptosis, and organ injury. Nicorandil should be explored further as a potential therapeutic strategy for limiting global IR injury during open-heart surgery in humans.
尼可地尔是一种三磷酸腺苷敏感钾通道激动剂和一氧化氮供体，是一种用于治疗缺血性胸痛的冠状动脉扩张剂，但它在体外循环（CPB）和心脏停搏的心脏直视手术中潜在的心脏保护益处尚未得到彻底研究。本研究的目的是在 CPB 加心脏停搏的心脏直视手术的既定实验模型中评估尼可地尔对术后心室功能障碍和终末器官损伤的影响。我们假设尼可地尔可减轻心肌缺血再灌注（IR）损伤，维持心室功能，并减少终末器官损伤。
兔子进行 CPB 插管，然后进行 60 分钟的主动脉夹闭（ACC）加冷心脏停搏，ACC 去除后 120 分钟恢复。ACC 前 5 分钟静脉给予尼可地尔（或生理盐水载体），并在整个恢复期间持续给予。连续记录左心室发展压（LVDP）、收缩性（LV + dp/dt）和舒张松弛（LV - dp/dt），并采集血液和组织样本以测量氧化应激（OS）、炎症、细胞凋亡和器官损伤。
与生理盐水对照组相比，尼可地尔显著减轻了 IR 引起的 LV 功能障碍（R-120：LV + dp/dt：1596 ± 397 对 514 ± 269 mmHg/s，p = 0.010；LV - dp/dt：-1524 ± 432 对-432 ± 243 mmHg/s，p < 0.001；LVDP：55 ± 11 对 22 ± 5 mmHg，p = 0.046）。此外，尼可地尔抑制了 IR 引起的 OS、炎症、细胞凋亡和器官损伤的增加。
尼可地尔通过减轻与 OS、炎症、细胞凋亡和器官损伤相关的 IR 引起的 LV 功能障碍来发挥心肌保护作用。尼可地尔作为一种限制体外循环心脏直视手术中全身 IR 损伤的潜在治疗策略，值得进一步探索。
