Department of Pharmacology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
Department of Physiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
Iran J Basic Med Sci. 2015 Jan;18(1):80-8.
This study aimed to examine the hypothesis that an antiarrhythmic effect might be obtained by ischemic preconditioning of the liver, and also to characterize the potential underlying mechanisms.
Male Wistar rats were anesthetized by thiopental sodium (50 mg/kg, IP) followed by IV injection of heparin (250 IU). Remote ischemic preconditioning (RIPC) was induced by 3 cycles of 5 min liver ischemia followed by 5 min of reperfusion. The hearts were excised within 5 min after the final cycle of preconditioning and perfused using Langendorff's system. The isolated perfused hearts were subjected to 30 min global ischemia followed by 90 min reperfusion. The myocardial arrhythmias induced by ischemia- reperfusion (I/R) were determined in accordance with the guidelines of Lambeth Conventions. The potential role of KATP channels on RIPC was assessed by injection of glibenclamide (nonselective KATP blocker) or 5-hydroxydecanoate (mitochondrial KATP blocker) on rats 30 and 15 min before induction of RIPC in the liver, respectively.
Hepatic remote preconditioning of the heart significantly (P<0.0001) prevented the incidence of myocardial arrhythmias induced by I/R in the perfused hearts (5.33±1.54 vs. 32.33±6.44,). However, the protective effects of remote preconditioning was significantly (P<0.01) abolished by the KATP blocker, glibenclamide (25.5±4.9 vs. 5.33±1.54,).
Hepatic RIPC may prevent the arrhythmias induced by I/R in the isolated perfused hearts via KATP channels.
本研究旨在检验肝脏缺血预处理可能产生抗心律失常作用的假说,并对潜在的作用机制进行研究。
雄性 Wistar 大鼠经硫喷妥钠(50mg/kg,IP)麻醉后,静脉注射肝素(250IU)。通过 3 个周期的 5 分钟肝脏缺血,再进行 5 分钟再灌注,诱导远程缺血预处理(RIPC)。在最后一个预处理周期结束后 5 分钟内取出心脏,并使用 Langendorff 系统进行灌流。将分离的灌流心脏进行 30 分钟的整体缺血,再进行 90 分钟的再灌注。根据 Lambeth 公约的指南,确定缺血-再灌注(I/R)引起的心肌心律失常。在诱导肝脏 RIPC 前 30 分钟和 15 分钟,分别向大鼠注射格列本脲(非选择性 KATP 阻滞剂)或 5-羟癸酸(线粒体 KATP 阻滞剂),以评估 KATP 通道在 RIPC 中的潜在作用。
心脏的肝脏远程预处理显著(P<0.0001)降低了灌流心脏 I/R 诱导的心肌心律失常的发生率(5.33±1.54 vs. 32.33±6.44)。然而,KATP 阻滞剂格列本脲显著(P<0.01)消除了远程预处理的保护作用(25.5±4.9 vs. 5.33±1.54)。
肝脏 RIPC 可能通过 KATP 通道预防分离灌流心脏 I/R 诱导的心律失常。