Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany.
Institute of Cardiovascular Physiology, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany.
Crit Care Med. 2019 Mar;47(3):e250-e255. doi: 10.1097/CCM.0000000000003629.
Remote ischemic preconditioning (RIPC) is a practicable and noninvasive method to protect the heart against ischemia reperfusion injury. Unfortunately results from clinical studies are not convincing. Propofol is suggested to be an inhibiting factor of cardioprotection by RIPC, but the underlying mechanism is still unknown. We investigated whether after RIPC the release of humoral factors and/or the direct cardioprotective effect at the myocardium is inhibited by propofol.
Randomized, prospective, blinded laboratory investigation.
Experimental laboratory.
PATIENTS/SUBJECTS: Male Wistar rats.
Repetitive hind limb ischemia in rats-blood plasma transfers to isolated rat heart.
In male Wistar rats (six groups, each n = 6/group), RIPC was induced by four cycles of 5 minutes bilateral hind limb ischemia alternately with 5 minutes of reperfusion. Blood samples were taken with (RIPC) and without RIPC (Con). Rats received continuous anesthesia with pentobarbital (Pento, 40 mg/kg body weight/hr) or propofol (Prop, 12 mg/kg body weight/hr), respectively. Cardioprotective properties of the blood plasma was investigated in the rat heart in vitro (six groups, each n = 6/group) perfused with Krebs-Henseleit buffer alone or with propofol (10 µM). Plasma was administered over 10 minutes before myocardial ischemia. All hearts underwent 33 minutes of global ischemia followed by 1 hour of reperfusion. At the end of the experiments, infarct size was determined by triphenyl-tetrazolium-chloride staining. RIPC plasma from pentobarbital anesthetized rats (Pento-RIPC) reduced infarct size from 64% (62-71%) (Pento-Con) to 34% (30-39%) (p < 0.0001). Infarct size with control plasma from propofol anesthetized rats was 59% (58-64%) (Prop-Con). RIPC plasma could not induce cardioprotection (Prop-RIPC: 63% [56-70%] ns vs Prop-Con). In contrast, RIPC plasma from pentobarbital anesthetized rats induced a significant infarct size reduction under propofol perfusion (Pento-RIPC: 34% [30-42%] vs Pento-Con: 54% [53-63%]; p < 0.0001).
Loss of cardioprotection by RIPC during propofol anesthesia depends on inhibition of release of humoral factors.
远程缺血预处理（RIPC）是一种可行且非侵入性的方法，可保护心脏免受缺血再灌注损伤。不幸的是，临床研究结果并不令人信服。丙泊酚被认为是 RIPC 心肌保护的抑制因子，但潜在机制尚不清楚。我们研究了 RIPC 是否会抑制体液因子的释放和/或心肌的直接保护作用。
随机、前瞻性、双盲实验室研究。
实验实验室。
患者/受试者：雄性 Wistar 大鼠。
大鼠反复下肢缺血-血液血浆转移至分离的大鼠心脏。
在雄性 Wistar 大鼠（六组，每组 n = 6/组）中，通过 4 个周期的双侧下肢缺血交替进行 RIPC，每次 5 分钟，每次 5 分钟再灌注。分别用戊巴比妥（RIPC 组和无 RIPC 组（Con））和丙泊酚（RIPC 组和无 RIPC 组（Prop））采血。大鼠分别用戊巴比妥（40mg/kg/体重/小时）或丙泊酚（12mg/kg/体重/小时）持续麻醉。在单独用 Krebs-Henseleit 缓冲液或用丙泊酚（10µM）灌注的大鼠心脏体外（六组，每组 n = 6/组）中研究了血浆的心脏保护特性。在心肌缺血前给予血浆 10 分钟。所有心脏均经历 33 分钟的全缺血，随后进行 1 小时的再灌注。实验结束时，通过三苯基四唑氯染色确定梗死面积。来自戊巴比妥麻醉大鼠的 RIPC 血浆（Pento-RIPC）将来自戊巴比妥麻醉大鼠的 RIPC 血浆（Pento-Con）的梗死面积从 64%（62-71%）减少至 34%（30-39%）（p < 0.0001）。来自丙泊酚麻醉大鼠的对照血浆的梗死面积为 59%（58-64%）（Prop-Con）。RIPC 血浆不能诱导心肌保护（Prop-RIPC：63%[56-70%]ns 与 Prop-Con）。相比之下，戊巴比妥麻醉大鼠的 RIPC 血浆在丙泊酚灌注下可显著减少梗死面积（Pento-RIPC：34%[30-42%]与 Pento-Con：54%[53-63%]；p < 0.0001）。
在丙泊酚麻醉期间，RIPC 丧失心肌保护作用取决于体液因子释放的抑制。
