Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, India.
Cardiovasc Ther. 2017 Oct;35(5). doi: 10.1111/1755-5922.12276.
Remote ischemic preconditioning (RIPC) is a phenomenon whereby transient nonlethal ischemia and reperfusion episodes confer protection against prolonged ischemia reperfusion-induced injury. However, the underlying intracellular signaling has not been extensively explored.
This study aimed to inspect the putative involvement of TRPV -dependent CGRP release in mediating remote hind limb preconditioning-induced cardioprotection.
In this study, remote hind limb preconditioning stimulus was delivered (four consecutive episodes of 5 minutes of ischemia reperfusion) using a blood pressure cuff tied at the inguinal level of the rat. The isolated rat hearts were perfused on the Langendorff's system and were subjected to 30-minutes global ischemia and 120-minutes reperfusion. Prolonged ischemia and subsequent reperfusion led to myocardial injury that was evaluated in terms of infarct size, LDH release, CK release, LVDP, +dp/dt , -dp/dt , and coronary flow rate. The pharmacological agents used in this study included capsaicin as TRPV channel activator, sumatriptan and CGRP8-37 as CGRP blockers.
Remote hind limb and capsaicin preconditioning (10 mg/kg ) significantly reduced the infarct size, LDH release, CK release and significantly improved LVDP, +dp/dt , -dp/dt , and coronary flow rate. However, remote hind limb and capsaicin preconditioning-induced cardioprotective effects were remarkably reduced in the presence of sumatriptan (8 mg/kg ) and CGRP8-37 (1 mg/kg ).
This indicates that remote hind limb preconditioning stimulus probably activates TRPV channels which subsequently induces CGRP release to produce cardioprotective effects.
远程缺血预处理（RIPC）是一种现象，即短暂的非致死性缺血和再灌注发作可防止长时间缺血再灌注引起的损伤。然而，其潜在的细胞内信号尚未得到广泛探索。
本研究旨在检查 TRPV 依赖性 CGRP 释放是否参与介导远程后肢预处理诱导的心脏保护作用。
在这项研究中，使用绑在大鼠腹股沟水平的血压袖带给予远程后肢预处理刺激（四个连续的 5 分钟缺血再灌注期）。分离的大鼠心脏在 Langendorff 系统上进行灌注，并进行 30 分钟的整体缺血和 120 分钟的再灌注。长时间的缺血和随后的再灌注导致心肌损伤，通过梗死面积、LDH 释放、CK 释放、LVDP、+dp/dt、-dp/dt 和冠状血流率来评估。本研究中使用的药理试剂包括辣椒素作为 TRPV 通道激活剂、舒马曲坦和 CGRP8-37 作为 CGRP 阻断剂。
远程后肢和辣椒素预处理（10mg/kg）显著减少了梗死面积、LDH 释放、CK 释放，并显著改善了 LVDP、+dp/dt、-dp/dt 和冠状血流率。然而，在舒马曲坦（8mg/kg）和 CGRP8-37（1mg/kg）存在的情况下，远程后肢和辣椒素预处理诱导的心脏保护作用显著降低。
这表明远程后肢预处理刺激可能激活 TRPV 通道，随后诱导 CGRP 释放产生心脏保护作用。
