Heart Research, Murdoch Children's Research Institute, Melbourne, Australia.
Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
Clin Exp Pharmacol Physiol. 2019 Nov;46(11):995-1000. doi: 10.1111/1440-1681.13150. Epub 2019 Aug 26.
Remote ischaemic preconditioning (RIPC) has been employed as a non-invasive protective intervention against myocardial ischaemia-reperfusion injury in animal studies. However, the underlying mechanisms are incompletely defined in humans and its clinical efficacy has been inconclusive. As advanced age, disease, and drugs may confound RIPC mechanisms in patients, our aim is to measure whether RIPC evokes release of adenosine, bradykinin, met-enkephalin, nitric oxide, and apolipoproteins in healthy young adults. Healthy subjects (n = 18, 9 males, 23 ± 1.5 years old; 9 females, 23 ± 1.8 years old) participated after informed consent. RIPC was applied using a blood pressure cuff to the dominant arms for four cycles of 5-minute cuff inflation (ischaemia) and 5-minute cuff deflation (reperfusion). Blood was sampled at baseline and immediately after the final cuff deflation (Post-RIPC). Baseline and Post-RIPC plasma levels of adenosine, bradykinin, met-enkephalin, apolipoprotein A-1 (ApoA-1), apolipoprotein D (ApoD), and nitric oxide (as nitrite) were measured via ELISA and high-performance liquid chromatography. Mean (±SD) baseline levels of adenosine, bradykinin, met-enkephalin, ApoA-1, ApoD, and nitrite in healthy young adults were 13.8 ± 6.5 ng/mL, 2.6 ± 1.9 μg/mL, 594.1 ± 197.4 pg/mL, 3.0 ± 0.7 mg/mL, 22.2 ± 4.0 μg/mL, and 49.8 ± 13.4 nmol/L, respectively. Post-RIPC adenosine and nitrite levels increased (59.5 ± 37.9%, P < .0001; 32.2 ± 19.5%, P < .0001), whereas met-enkephalin and ApoD levels marginally decreased (5.3 ± 14.0%, P = .04; 10.8 ± 20.5%, P = .04). Post-RIPC levels were not influenced by sex, age, blood pressure, waist circumference, or BMI. RIPC produces increased levels of adenosine and nitrites, and decreased met-enkephalin and ApoD in the plasma of young healthy adults.
远程缺血预处理 (RIPC) 已被用作动物研究中预防心肌缺血再灌注损伤的非侵入性保护干预措施。然而,其在人体中的潜在机制尚不完全明确,其临床疗效也尚无定论。由于年龄增长、疾病和药物可能会使患者的 RIPC 机制复杂化,因此我们的目的是测量 RIPC 是否会在健康年轻成年人中引发腺苷、缓激肽、甲硫氨酸脑啡肽、一氧化氮和载脂蛋白的释放。在知情同意后,18 名健康受试者(9 名男性,23 ± 1.5 岁;9 名女性,23 ± 1.8 岁)参与了研究。使用血压袖带对优势臂施加 RIPC,袖带充气(缺血)和放气(再灌注)各持续 5 分钟,共进行 4 个循环。在基线和最后一次袖带放气后立即(Post-RIPC)取样。通过 ELISA 和高效液相色谱法测量基线和 Post-RIPC 时血浆中的腺苷、缓激肽、甲硫氨酸脑啡肽、载脂蛋白 A-1(ApoA-1)、载脂蛋白 D(ApoD)和一氧化氮(以亚硝酸盐形式)的水平。健康年轻成年人的腺苷、缓激肽、甲硫氨酸脑啡肽、ApoA-1、ApoD 和亚硝酸盐的平均(±SD)基线水平分别为 13.8 ± 6.5 ng/mL、2.6 ± 1.9 μg/mL、594.1 ± 197.4 pg/mL、3.0 ± 0.7 mg/mL、22.2 ± 4.0 μg/mL 和 49.8 ± 13.4 nmol/L。Post-RIPC 时,腺苷和亚硝酸盐水平升高(59.5 ± 37.9%,P <.0001;32.2 ± 19.5%,P <.0001),而甲硫氨酸脑啡肽和 ApoD 水平略有下降(5.3 ± 14.0%,P =.04;10.8 ± 20.5%,P =.04)。Post-RIPC 水平不受性别、年龄、血压、腰围或 BMI 的影响。RIPC 可使年轻健康成年人的血浆中腺苷和亚硝酸盐水平升高,而甲硫氨酸脑啡肽和 ApoD 水平降低。