Remote ischemic preconditioning regulates HIF-1α levels, apoptosis and inflammation in heart tissue of cardiosurgical patients: a pilot experimental study
Remote ischemic preconditioning regulates HIF-1α levels, apoptosis and inflammation in heart tissue of cardiosurgical patients: a pilot experimental study
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DOI：
10.1007/s00395-012-0314-0
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发表时间：
2013-01-01
影响因子：
9.5
通讯作者：
Meybohm, Patrick
中科院分区：
文献类型：
--
作者：
Albrecht, Martin;Zitta, Karina;Meybohm, Patrick
远端器官的短暂缺血（远端缺血预处理，RIPC）具有减轻心肌损伤的潜力，但其潜在机制尚不清楚。在初步实验研究中，我们研究了RIPC在心肺转流（CPB）心脏手术患者心脏组织中的细胞和分子效应，重点关注凋亡事件、局部和全身炎症以及缺氧诱导因子-1 α（HIF-1 α）的调节。使用血压袖带通过4个5分钟周期的短暂上肢缺血/再灌注诱导RIPC。在CPB前后从接受RIPC的患者（N = 32）和对照患者（N = 29）获得右心房组织和血清。RIPC患者在手术后前48小时内显示肌钙蛋白T血清浓度降低（与对照组相比P < 0.05），表明RIPC具有心脏保护作用。CPB前采集的RIPC患者的样本含有显著增加量的HIF-1 α和半胱天冬酶原-3（HIF-1 α：P < 0.05 vs. control，半胱天冬酶原-3：P < 0.05 vs. control），而半胱天冬酶3和7的活性呈下降趋势。CPB后采集的RIPC患者样本显示髓过氧化物酶活性增加（与对照组相比P < 0.05;与CPB前RIPC相比P < 0.05）以及白细胞介素（IL）-1 β组织浓度升高（与CPB前RIPC相比P < 0.05）。CPB前RIPC患者血清IL-8、IL-1 β和TNF α水平显著高于对照组（P < 0.05）。总之，RIPC调节心脏手术患者心肌中的HIF-1 α水平、细胞凋亡和炎症，并导致循环细胞因子浓度增加。
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-1 alpha (HIF-1 alpha). 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-1 alpha and procaspase-3 (HIF-1 alpha: 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)-1 beta (P < 0.05 vs. RIPC before CPB). Serum levels of IL-8, IL-1 beta and TNF alpha were significantly increased in RIPC patients before CPB (P < 0.05 vs. control before CPB). In summary, RIPC regulates HIF-1 alpha levels, apoptosis and inflammation in the myocardium of cardiosurgical patients and leads to increased concentrations of circulating cytokines.