Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei, China.
J Cell Biochem. 2020 Nov;121(11):4535-4541. doi: 10.1002/jcb.29671. Epub 2020 Feb 7.
The cardioprotection of remote ischemic preconditioning (RIPC) is abolished under propofol maintained anesthesia. Transient receptor potential vanilloid 1 (TRPV1) channel is present in the heart, and its activation could induce cardioprotection. Therefore, we tested whether the anesthetic propofol administration phase interfered with the RIPC-induced cardioprotection, and RIPC-induced cardioprotection via the cardiac TRPV1 channel. Male Sprague-Dawley rats were subjected to myocardial 30 minutes of ischemia followed by 2 hours of reperfusion. RIPC consisted of three cycles of 5-minute ischemia/reperfusion applied to a hindlimb. Propofol infusion at 12 mg/kg/h was commenced either at 10 minutes before the start of RIPC in the P-pre + RIPC group, or immediately after myocardial ischemia at the onset of reperfusion (P-post + RIPC) while performing RIPC. These two propofol infusion regimes were applied to another two grou bs without RIPC (P-pre and P-post groups). Infarct size (IS) was assessed by triphenyltetrazolium staining. Heart TRPV1 expression was detected by Western blot and immunofluorescence. RIPC significantly reduced myocardial IS compared with the control group (36.7 ± 3% versus 57.2 ± 4%; P < .01). When propofol was started before RIPC, the IS sparing effect of RIPC was completely abolished. However, propofol infusion starting immediately after myocardial ischemia did not affect RIPC-induced cardioprotection. TRPV1 expression significant increase after RIPC, then propofol inhibited the TRPV1 activation of RIPC if given before RIPC but not after. Our results suggest that the timing of propofol administration is critical to preserve the cardioprotection of RIPC. Propofol might cancel RIPC-induced cardioprotection via the cardiac TRPV1 receptor.
远程缺血预处理 (RIPC) 的心脏保护作用在异丙酚维持的麻醉下被消除。瞬时受体电位香草酸 1 型 (TRPV1) 通道存在于心脏中，其激活可诱导心脏保护。因此，我们测试了麻醉异丙酚给药阶段是否会干扰 RIPC 诱导的心脏保护作用，以及 RIPC 通过心脏 TRPV1 通道诱导的心脏保护作用。雄性 Sprague-Dawley 大鼠接受 30 分钟心肌缺血，随后再灌注 2 小时。RIPC 由三个 5 分钟的缺血/再灌注循环组成，施加于后肢。异丙酚输注以 12mg/kg/h 的剂量在 RIPC 开始前 10 分钟开始（P-pre+RIPC 组），或在再灌注开始时（再灌注后开始）立即开始（P-post+RIPC 组），同时进行 RIPC。另外两组没有进行 RIPC（P-pre 和 P-post 组）。用三苯基四氮唑染色评估梗塞面积（IS）。通过 Western blot 和免疫荧光检测心脏 TRPV1 表达。与对照组相比，RIPC 显著减少心肌 IS（36.7±3%对 57.2±4%；P<.01）。当异丙酚在 RIPC 之前开始时，RIPC 的 IS 节约作用完全被消除。然而，心肌缺血后立即开始输注异丙酚并不影响 RIPC 诱导的心脏保护作用。RIPC 后 TRPV1 表达明显增加，然后异丙酚在 RIPC 之前给药时抑制 RIPC 诱导的 TRPV1 激活，但在 RIPC 之后则不抑制。我们的结果表明，异丙酚给药的时间对于维持 RIPC 的心脏保护作用至关重要。异丙酚可能通过心脏 TRPV1 受体取消 RIPC 诱导的心脏保护作用。
