Institute for Pathophysiology, West German Heart and Vascular Centre, University of Essen Medical School, Essen, Germany.
Laboratory of Pharmacology, National and Kapodistrian University of Athens, Athens, Greece.
Cardiovasc Drugs Ther. 2023 Oct;37(5):865-876. doi: 10.1007/s10557-022-07345-9. Epub 2022 May 21.
The role of platelets during myocardial ischemia/reperfusion (I/R) is ambivalent. They contribute to injury but also to cardioprotection. Repeated blood flow restriction and reperfusion in a tissue/organ remote from the heart (remote ischemic conditioning, RIC) reduce myocardial I/R injury and attenuate platelet activation. Whether or not platelets mediate RIC's cardioprotective signal is currently unclear.
Venous blood from healthy volunteers (without or with pretreatment of 500/1000 mg aspirin or 180 mg ticagrelor orally, 2-3 h before the study, n = 18 each) was collected before and after RIC (3 × 5 min blood pressure cuff inflation at 200 mmHg on the left upper arm/5 min deflation). Washed platelets were isolated. Platelet-poor plasma was used to prepare plasma-dialysates. Platelets (25 × 10/µL) or plasma-dialysates (1:10) prepared before and after RIC from untreated versus aspirin- or ticagrelor-pretreated volunteers, respectively, were infused into isolated buffer-perfused rat hearts. Hearts were subjected to global 30 min/120 min I/R. Infarct size was stained. Infarct size was less with infusion of platelets/plasma-dialysate after RIC (18 ± 7%/23 ± 9% of ventricular mass) than with platelets/plasma-dialysate before RIC (34 ± 7%/33 ± 8%). Aspirin pretreatment abrogated the transfer of RIC's cardioprotection by platelets (after/before RIC, 34 ± 7%/33 ± 7%) but only attenuated that by plasma-dialysate (after/before RIC, 26 ± 8%/32 ± 5%). Ticagrelor pretreatment induced an in vivo formation of cardioprotective factor(s) per se (platelets/plasma-dialysate before RIC, 26 ± 7%/26 ± 7%) but did not impact on RIC's cardioprotection by platelets/plasma-dialysate (20 ± 7%/21 ± 5%).
Platelets serve as carriers for RIC's cardioprotective signal through an aspirin-sensitive and thus cyclooxygenase-dependent mechanism. The P2Y inhibitor ticagrelor per se induces a humoral cardioprotective signal.
血小板在心肌缺血/再灌注（I/R）过程中的作用是矛盾的。它们既有助于损伤，也有助于心脏保护。心脏以外的组织/器官的反复血流限制和再灌注（远程缺血预处理，RIC）可减少心肌 I/R 损伤并减弱血小板激活。血小板是否介导 RIC 的心脏保护信号目前尚不清楚。
健康志愿者（无或用 500/1000mg 阿司匹林或 180mg 替格瑞洛口服预处理，研究前 2-3 小时，每组 18 人）静脉采血，在 RIC 前后（左上肢 200mmHg 血压袖带充气 3×5 分钟/5 分钟放气）。分离血小板。用血小板少的血浆制备血浆透析液。分别从未经处理的志愿者和阿司匹林或替格瑞洛预处理的志愿者中分离 RIC 前后的血小板（25×10/µL）或血浆透析液（1:10），将其注入分离的缓冲灌注大鼠心脏。心脏受到 30 分钟/120 分钟的整体 I/R 处理。对梗塞面积进行染色。与 RIC 前相比，RIC 后输注血小板/血浆透析液可减少梗塞面积（心室质量的 18±7%/23±9%）（34±7%/33±8%）。阿司匹林预处理可阻断血小板传递 RIC 的心脏保护作用（RIC 前后，34±7%/33±7%），但仅减弱了血浆透析液的传递（RIC 前后，26±8%/32±5%）。替格瑞洛预处理可诱导体内形成本身具有心脏保护作用的因子（RIC 前的血小板/血浆透析液，26±7%/26±7%），但不影响血小板/血浆透析液的 RIC 心脏保护作用（20±7%/21±5%）。
血小板通过阿司匹林敏感且因此环氧化酶依赖的机制作为 RIC 心脏保护信号的载体。P2Y 抑制剂替格瑞洛本身可诱导体液心脏保护信号。
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