Interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic preconditioning during coronary artery bypass grafting

Interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic preconditioning during coronary artery bypass grafting
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DOI:
10.1016/j.jtcvs.2013.01.005
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发表时间:
2014-01-01
影响因子:
6
通讯作者:
Heusch, Gerd
Heusch, Gerd
中科院分区:
医学1区
文献类型:
--
作者:
Kottenberg, Eva;Musiolik, Judith;Heusch, Gerd

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目的:远程缺血预处理对心肌缺血/再灌注损伤具有保护作用。我们最近发现,在异氟烷麻醉期间接受冠状动脉旁路移植术的患者左心室活检标本中,远程缺血预处理的保护作用与信号转导子和转录激活因子5的激活有关。由于丙泊酚麻醉时远端缺血预处理对心脏没有保护作用,我们假设丙泊酚麻醉干扰了信号转导子和转录激活子5的激活。在一项随机、单盲、安慰剂对照、前瞻性研究中,我们分析了24名非糖尿病患者在丙泊酚麻醉期间(有或没有远端缺血预处理)的一系列心脏保护蛋白,结果:与非远程缺血预处理(n = 12)相比,远程缺血预处理(n = 12)未能降低肌钙蛋白I时间曲线下面积(273 +/- 184 ng/mL x 72小时vs 365 +/- 301 ng/mL x 72小时; P = 0.374)。尽管从基线到再灌注,几种蛋白激酶的磷酸化增加,但信号转导和转录激活因子5磷酸化没有增加,并且在远程缺血预处理组和非远程缺血预处理组之间没有差异。丙泊酚麻醉期间的远程缺血预处理未引起信号转导子和转录激活子5激活或心脏保护,这表明丙泊酚与信号转导子和转录激活子上游的心脏保护信号相互作用5。
Objective: Remote ischemic preconditioning protects the myocardium from ischemia/reperfusion injury. We recently identified protection by remote ischemic preconditioning to be associated with the activation of signal transducer and activator of transcription 5 in left ventricular biopsy specimens of patients undergoing coronary artery bypass grafting during isoflurane anesthesia. Because remote ischemic preconditioning did not protect the heart during propofol anesthesia, we hypothesized that propofol anesthesia interferes with signal transducer and activator of transcription 5 activation.Methods: In a randomized, single-blind, placebo-controlled, prospective study, we analyzed an array of established cardioprotective proteins during propofol anesthesia with or without remote ischemic preconditioning in 24 nondiabetic patients with 3-vessel coronary artery disease.Results: Remote ischemic preconditioning (n = 12) compared with no remote ischemic preconditioning (n = 12) failed to decrease the area under the troponin I time curve (273 +/- 184 ng/mL x 72 hours vs 365 +/- 301 ng/mL x 72 hours; P = .374). Although phosphorylation of several protein kinases was increased from baseline to reperfusion, signal transducer and activator of transcription 5 phosphorylation was not increased and was not different between the remote ischemic preconditioning and no remote ischemic preconditioning groups.Conclusions: Remote ischemic preconditioning during propofol anesthesia did not evoke either signal transducer and activator of transcription 5 activation or cardioprotection, implying interaction of propofol with cardioprotective signaling upstream of signal transducer and activator of transcription 5.