Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Schwanenweg 21, 24105 Kiel, Germany.
Basic Res Cardiol. 2013 Jan;108(1):314. doi: 10.1007/s00395-012-0314-0. Epub 2012 Dec 1.
Transient episodes of ischemia in a remote organ (remote ischemic preconditioning, RIPC) bears the potential to attenuate myocardial injury, but the underlying mechanisms are only poorly understood. In the pilot experimental study presented we investigated cellular and molecular effects of RIPC in heart tissue of cardiosurgical patients with cardiopulmonary bypass (CPB) and focussed on apoptotic events, local and systemic inflammation as well as the regulation of the hypoxia induced factor-1α (HIF-1α). RIPC was induced by four 5-min cycles of transient upper limb ischemia/reperfusion using a blood-pressure cuff. Right atrial tissue and serum were obtained from patients receiving RIPC (N = 32) and control patients (N = 29) before and after CPB. RIPC patients showed reduced troponin T serum concentrations in the first 48 h after surgery (P < 0.05 vs. control) indicating cardioprotective effects of RIPC. Samples from RIPC patients that were collected before CPB contained significantly increased amounts of HIF-1α and procaspase-3 (HIF-1α: P < 0.05 vs. control, procaspase-3: P < 0.05 vs. control), whereas activities of caspases 3 and 7 were by trend reduced. Samples from RIPC patients that were taken after CPB showed an increased activity of myeloperoxidase (P < 0.05 vs. control; P < 0.05 vs. RIPC before CPB) as well as elevated tissue concentrations of the interleukin (IL)-1β (P < 0.05 vs. RIPC before CPB). Serum levels of IL-8, IL-1β and TNFα were significantly increased in RIPC patients before CPB (P < 0.05 vs. control before CPB). In summary, RIPC regulates HIF-1α levels, apoptosis and inflammation in the myocardium of cardiosurgical patients and leads to increased concentrations of circulating cytokines.
远程器官的短暂缺血发作（远程缺血预处理，RIPC）有可能减轻心肌损伤，但潜在机制尚不清楚。在本研究中，我们研究了心肺旁路（CPB）下心脏手术患者心脏组织中 RIPC 的细胞和分子效应，并重点关注细胞凋亡、局部和全身炎症以及缺氧诱导因子-1α（HIF-1α）的调节。通过血压袖带对 4 名患者进行 5 分钟的上肢缺血/再灌注循环来诱导 RIPC。在 CPB 前后，分别从接受 RIPC（N = 32）和对照组患者（N = 29）中获得右心房组织和血清。与对照组相比，RIPC 患者术后 48 小时内血清肌钙蛋白 T 浓度降低（P < 0.05），表明 RIPC 具有心脏保护作用。与对照组相比，RIPC 患者在 CPB 前采集的样本中 HIF-1α 和前半胱氨酸蛋白酶-3（procaspase-3）的含量显著增加（HIF-1α：P < 0.05，procaspase-3：P < 0.05），而半胱氨酸蛋白酶 3 和 7 的活性则呈下降趋势。与 CPB 前相比，RIPC 患者在 CPB 后采集的样本中髓过氧化物酶的活性增加（P < 0.05；P < 0.05），白细胞介素（IL）-1β 的组织浓度也升高（P < 0.05）。与 CPB 前相比，RIPC 患者的血清白细胞介素（IL）-8、IL-1β 和 TNFα 水平显著升高（P < 0.05）。总之，RIPC 调节心脏手术患者心肌中的 HIF-1α 水平、细胞凋亡和炎症，并导致循环细胞因子浓度增加。
