Müllenheim Jost, Ebel Dirk, Bauer Mirco, Otto Florian, Heinen André, Frässdorf Jan, Preckel Benedikt, Schlack Wolfgang
Klinik für Anaesthesiologie, Universitätsklinikum, Duesseldorf, Germany.
Anesthesiology. 2003 Sep;99(3):624-31. doi: 10.1097/00000542-200309000-00017.
Sevoflurane exerts cardioprotective effects that mimic the early ischemic preconditioning phenomenon (EPC) by activating adenosine triphosphate-sensitive potassium (KATP) channels. Ischemic late preconditioning (LPC) is an important cardioprotective mechanism in patients with coronary artery disease. The authors investigated whether the combination of LPC and sevoflurane-induced preconditioning results in enhanced cardioprotection and whether opening of KATP channels plays a role in this new setting.
Seventy-three rabbits were instrumented with a coronary artery occluder. After recovery for 10 days, they were subjected to 30 min of coronary artery occlusion and 120 min of reperfusion (I/R). Controls (n = 14) were not preconditioned. LPC was induced in conscious animals by a 5-min period of coronary artery occlusion 24 h before I/R (LPC, n = 15). Additional EPC was induced by a 5-min period of myocardial ischemia 10 min before I/R (LPC+EPC, n = 9). Animals of the sevoflurane (SEVO) groups inhaled 1 minimum alveolar concentration of sevoflurane for 5 min at 10 min before I/R with (LPC+SEVO, n = 10) or without (SEVO, n = 15) additional LPC. The KATP channel blocker 5-hydroxydecanoate (5-HD, 5 mg/kg) was given intravenously 10 min before sevoflurane administration (LPC+SEVO+5-HD, n = 10).
Infarct size of the area at risk (triphenyltetrazolium staining) was reduced from 45 +/- 16% (mean+/-SD, control) to 27 +/- 11% by LPC (P < 0.001) and to 27 +/- 17% by sevoflurane (P = 0.001). Additional sevoflurane administration after LPC led to a further infarct size reduction to 14 +/- 8% (LPC+SEVO, P = 0.003 vs. LPC; P = 0.032 vs. SEVO), similar to the combination of LPC and EPC (12 +/- 8%; P = 0.55 vs. LPC+SEVO). Cardioprotection induced by LPC+SEVO was abolished by 5-HD (LPC+SEVO+5-HD, 41 +/- 19%, P = 0.001 vs. LPC+SEVO).
Sevoflurane administration confers additional cardioprotection after LPC by opening of KATP channels.
七氟醚通过激活三磷酸腺苷敏感性钾（KATP）通道发挥心脏保护作用，模拟早期缺血预处理现象（EPC）。缺血晚期预处理（LPC）是冠心病患者重要的心脏保护机制。作者研究了LPC与七氟醚诱导的预处理联合应用是否能增强心脏保护作用，以及KATP通道开放在此新情况下是否起作用。
73只兔子植入冠状动脉阻塞器。恢复10天后，进行30分钟冠状动脉阻塞和120分钟再灌注（I/R）。对照组（n = 14）未进行预处理。在I/R前24小时对清醒动物进行5分钟冠状动脉阻塞诱导LPC（LPC组，n = 15）。在I/R前10分钟进行5分钟心肌缺血诱导额外的EPC（LPC+EPC组，n = 9）。七氟醚（SEVO）组动物在I/R前10分钟吸入1最低肺泡浓度七氟醚5分钟，其中一组在诱导LPC后进行（LPC+SEVO组，n = 10），另一组未进行额外LPC（SEVO组，n = 15）。在给予七氟醚前10分钟静脉注射KATP通道阻滞剂5-羟基癸酸（5-HD，5 mg/kg）（LPC+SEVO+5-HD组，n = 10）。
通过LPC，危险区域梗死面积（三苯基四氮唑染色）从45±16%（平均值±标准差，对照组）降至27±11%（P < 0.001），七氟醚使其降至27±17%（P = 0.001）。LPC后额外给予七氟醚导致梗死面积进一步降至14±8%（LPC+SEVO组，与LPC组相比P = 0.003；与SEVO组相比P = 0.032），类似于LPC与EPC联合应用（12±8%；与LPC+SEVO组相比P = 0.55）。5-HD消除了LPC+SEVO诱导的心脏保护作用（LPC+SEVO+5-HD组，41±19%，与LPC+SEVO组相比P = 0.001）。
七氟醚给药通过开放KATP通道在LPC后赋予额外的心脏保护作用。
